NHMRC Research Achievements - SUMMARY
FUNDED RESEARCH INTO INJURY RELATED RESEARCH
ENDING 2004 TO 2013
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Australian National University
Brain Research Institute
Centenary Institute of Cancer Medicine and Cell Biology
Centre for Eye Research Australia Ltd
Curtin University of Technology
Edith Cowan University
Flinders University
Garvan Institute of Medical Research
Griffith University
Howard Florey Institute
Injury Prevention and Control (Australia) Ltd
Institute of Medical and Veterinary Science
La Trobe University
Macquarie University
Mater Medical Research Institute, Brisbane
Melbourne Health
Menzies Research Institute
Menzies School of Health Research
Monash University
Murdoch Childrens Research Institute
Murdoch University
National Stroke Foundation
Prince Henry's Institute of Medical Research
Queensland University of Technology
Repatriation General Hospital, Daw Park
RMIT University
Royal Prince Alfred Hospital
Sir Charles Gairdner Hospital
University of Adelaide
University of Ballarat
University of Melbourne
University of New South Wales
University of Newcastle
University of Queensland
University of South Australia
University of Sydney
University of Tasmania
University of Technology Sydney
NHMRC Research Achievements - SUMMARY
University of Western Australia
University of Western Sydney
University of Wollongong
Victor Chang Cardiac Research Institute
Victoria University
NHMRC Research Achievements - SUMMARY
Grant ID: 316951
CIA Name: Prof James Butler
Admin Inst: Australian National University
Main RFCD: Health Economics
Total funding: $4,500,000
Start Year: 2005
End Year: 2012
Grant Type: NHMRC Strategic Awards
Title of research award:
ACERH- Inovative analyses of health insurance, ageing and the economic burden of illness and injuryACERHInovative analyses of health insurance, ageing and the economic burden of illness and injury
Lay Description (from application):
An inter-university collaborative research centre – the Australian Centre for Economic Research on Health
(ACERH) – will be established, undertaking applied health economics research within three research programs:
health insurance; ageing; and the economic analysis of illness and injury. ACERH will develop a unique, unit
record, linked data set, including data from private health insurance partners, providing longitudinal data on
health service utilisation in both public and private sectors.
Research achievements (from final report):
This grant was used to establish a new inter-university centre - the Australian Centre for Economic Research
on Health (ACERH). Over the life of the Centre, research was undertaken on a range of topics primarily in
health insurance and health care financing, the economic burden of illness and the cost-effectiveness of
interventions to reduce that burden, and the economics of ageing and aged care. Selected research highlights
included work on the economic aspects of health insurance arrangements in Australia and proposals for reform,
including an "opt-out" option for Medicare, analysis of the risk equalisation scheme for private health insurers,
and a proposal for a Medicare Hospital Benefits scheme (some aspects of which are manifest in the new public
hospital payment scheme currently being implemented by the Australian and State Governments). Other
significant research in the area of child health in Australia found that, although an increasing income gradient
by child age exists when the same covariates used in other international studies are included, the gradient
disappears when a richer set of control variables including parental health is included. Other significant and
policy-relevant research included an economic evaluation of alternative HPV vaccination strategies in
Australia, and a critical appraisal of government policy on GP Super Clinics. Extensive research has also been
undertaken on economic aspects of breastfeeding, resulting in an ACERH research fellow receiving several
invitations to provide advice internationally on public policy in this area.
Expected future outcomes:
Through its research outputs, and contribution to capacity building through the development of a cadre of PhD
students and early career researchers, ACERH's legacy will be its contributions to health policy debates and its
strengthening of the health economics workforce. This legacy will be evident for some time in the future.
Name of contact:
Jim Butler
Email/Phone no. of contact:
jim.butler@anu.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 471418
CIA Name: Prof Angela Dulhunty
Admin Inst: Australian National University
Main RFCD: Peripheral Nervous System
Total funding: $603,100
Start Year: 2008
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
Communication between calcium ion channels in skeletal muscle excitation-contraction
couplingCommunication between calcium ion channels in skeletal muscle excitation-contraction coupling
Lay Description (from application):
Ageing, injury, drugs or genetic defects cause muscle weakness, prevent exercise, compromise life style and
contribute to poor health and osteoporosis. In order to move signals travel from our brain to muscles, where
one calcium ion channel detects the signal and tells a second calcium channel to open and release calcium ions
to initiate contraction. The project will pave the way for developing drugs to help with muscle disorders by
trageting the site of interaction between the channels.
Research achievements (from final report):
Work supported by this grant enabled us to perform the first study of the second of three SPRY domains in the
skeletal muscle ryanodine receptor (RyR1). In this comprehensive work we used NMR, CD to examine the
structure the recombinant DHPR II-III loop bound to the SPRY2 domain of RyR1 and cryoelectron microscopy
to locate the domain in the RyR protein (Cui et al., 2009; Tae et al., 2009; Tae et al., 2011; Perálvarez-Marín et
al., 2011). We quantified DHPR alpha1s II-III loop, and the variably spliced AS1 region of RyR1, binding to
SPRY2. Mutation of specific acidic residues in SPRY2 or basic residues in the II-III loop or in the ASI region,
prevent the ASI/SPRY2 binding (Tae et al., 2009). A cyclised II-III loop was expressed using novel intein
technology and is a stronger activator of RyR1 that the linear version of the loop (Tae et al. 2011b). In an elite
international collaboration we show that mutation of the critical regions in the SPRY2 domain do not influence
EC coupling (Tae et al., 2011a), indicating unexpectedly, that there is a specific influence of the DHPR
complex on interactions of the SPRY2 domain, possibly involving the intracellular β1a subunit of the DHPR.
The grant further supported preliminary paradigm shifting work with the DHPR β1a subunit, and a peptide
corresponding to its C-tail, both of which bind to and activate RyR1 with pM affinity, supporting a role for β1a
in excitation-contraction coupling (Karunasekera et al., 2009; Rebbeck et al., 2011).
Expected future outcomes:
We have identified the SPRY2 domain as a potential therapeutic target for modulating calcium release through
RyR1, and thus skeletal muscle contraction. The β1a work provided background for current studies of β1a
interactions with RyR1 and the alpha1S II-III loop and mechanisms that allow β1a to contribute to EC coupling
Name of contact:
Angela Dulhunty
Email/Phone no. of contact:
angela.dulhunty@anu.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 157307
CIA Name: A/Pr Paul McCrory
Admin Inst: Brain Research Institute
Main RFCD: Sports Medicine
Total funding: $130,807
Start Year: 2001
End Year: 2004
Grant Type: Early Career Fellowships (Australia)
Title of research award:
Prospective validation of an ass. and outcome scale for mild traumatic brain injury & to det. the influence of
ApoE susProspective validation of an ass. and outcome scale for mild traumatic brain injury & to det. the
influence of ApoE sus
Lay Description (from application):
Not Available
Research achievements (from final report):
Mild traumatic brain injury has the potential to cause significant morbidity due to its effects on cognitive and
psychological function. The condition also has significant social costs in terms of work absenteeism,
hospital/medical costs and possible impairment in school performance in younger people. This study developed
an assessment scale which may have widespread application in emergency departments, general medical
practice, and sports medicine as well as in rehabilitation settings. This scale has now been incorporated into
international guidelines for the management of sports concussion. In addition, the characterization of specific
sequelae of head injury such as concussive convulsions and second impact syndrome has enabled clinicians to
manage these conditions using an evidence-based approach.
Expected future outcomes:
The work will have two broad outcomes. Firstly, the adoption internationally of evidence-based management
guidelines and second, the ongoing development of computerised cognitive screening strategies which will
simplify the neurocognitive assessment of head injured patients of all ages.
Name of contact:
Paul Mccrory
Email/Phone no. of contact:
paulmccr@bigpond.net.au
NHMRC Research Achievements - SUMMARY
Grant ID: 527925
CIA Name: Dr Michael Makdissi
Admin Inst: Brain Research Institute
Main RFCD: Peripheral Nervous System
Total funding: $176,719
Start Year: 2009
End Year: 2012
Grant Type: Early Career Fellowships (Australia)
Title of research award:
Functional neuroimaging in mild traumatic brain injuryFunctional neuroimaging in mild traumatic brain injury
Lay Description (from application):
Mild traumatic brain injury (mTBI) represents a significant public health issue in Australian communities.
Complications can include prolonged symptoms, depression and progressive deterioration of brain function.
Clinical management of mTBI hinges on accurate assessment of recovery. The aim of the current study is to
investigate the role of novel functional brain imaging techniques such as diffusion tensor imaging and
connectivity studies, in the assessment of brain disturbance following mTBI.
Research achievements (from final report):
Mild traumatic brain injury (TBI) represents a significant public health issue in Australian communities. It is
commonly observed in sporting populations and following motor vehicle trauma. Whilst many patients recover
uneventfully following mild TBI, some individuals have prolonged and debilitating symptoms and/or cognitive
deficits in the acute setting. Moreover, mild TBI has been associated with increased risk of depression and
long-term deterioration of brain function resulting in early dementia.Clinical management of mild TBI hinges
on accurate assessment of recovery following injury. Practical assessment however is limited by the absence of
an objective biomarker to directly quantify pathophysiological changes associated with mild TBI. Surrogate
measures of brain function currently used in the clinical setting include self-reported symptoms, clinical tests of
balance and screening cognitive test batteries, all of which have significant limitations regarding reliability,
sensitivity and specificity.Although the pathophysiology of mild TBI remains unclear, data derived from
animal models of head injury suggest that linear acceleration or rotational shearing forces result in a cascade of
neurochemical, metabolic or gene-expression changes. Whilst conventional structural neuroimaging modalities
are typically normal, advanced neuroimaging techniques may provide a direct measure of pathophysiological
changes following mTBI. The current study provided prelimiary data on the role of advanced neuroimaging
techniques in the assessment of brain disturbance using concussion in sport as a model for mild TBI.
Expected future outcomes:
Understanding the pathophysiology would be expected to lead to an improvement in the assessment of
recovery following mild TBI and facilitate accurate classification of injury severity and risk of long-term
complications. Ultimately, this would be expected to lead to the development of specific treatment and
prevention strategies to reduce the morbidity and risks associated with mild TBI.
Name of contact:
Michael Makdissi
Email/Phone no. of contact:
makdissi@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 183770
Start Year: 2002
CIA Name: Dr Nicholas Shackel
End Year: 2005
Admin Inst: Centenary Institute of Cancer Medicine and Cell Biology
Fellowships (Overseas)
Main RFCD: Gastroenterology and Hepatology
Total funding: $233,168
Grant Type: Early Career
Title of research award:
Differential gene expression in hepatic wound healing.Differential gene expression in hepatic wound healing.
Lay Description (from application):
Not Available
Research achievements (from final report):
The C.J. Martin was an invaluable opportunity enabling me to be trained in a number of important laboratory
techniques not commonly performed within Australia. This included the isolation of primary cells from liver
tissue, the use of therpaeutic stem cells and viral transduction. Additonal outcomes of the C.J. Martin included
the establishment of long-term collaborations within the USA and especially at Duke University and to-date the
publication of three peer-reviewed mansucripts.
Expected future outcomes:
The ongoing long-term collobartion with researchers at Duke University and a further three published
manuscripts are in preperation.
Name of contact:
Dr Nicholas Shackel
Email/Phone no. of contact:
n.shackel@centenary.usyd.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 529918
Start Year: 2009
CIA Name: Prof Jonathan Crowston
End Year: 2011
Admin Inst: Centre for Eye Research Australia Ltd Grant Type: NHMRC Project Grants
Main RFCD: Surgery
Total funding: $280,400
Title of research award:
The impact of fluid mechanics on wound healing after glaucoma surgery- an engineering-based approachThe
impact of fluid mechanics on wound healing after glaucoma surgery- an engineering-based approach
Lay Description (from application):
Excess scarring after glaucoma surgery is the major reason why surgery fails.This study will investigate how
biomechanical forces in the eye influence wound healing and provide a new approach to regulating scar
formation. This will provide key information for developing surgical techniques that improve outcome and
prevent vision loss. The annual cost to Australia from vision loss due to glaucoma will double to $4.3 billion
by 2025 unless better treatments are developed (Access Economics).
Research achievements (from final report):
, Glaucoma is the second leading cause of blindness worldwide and effects 1 in 10 Australians over the age of
80. Successful glaucoma filtration surgery is the most effective treatment for lowering intraocular pressure
(IOP) and preventing vision loss in glaucoma. The success of filtration surgery is dependent on interrupting the
wound healing response, where scar formation frequently leads to surgical failure. We wished to use
experimental measurements and computational modelling to determine the optimal physical conditions to
reduce post-operative scarring., , We created a biomechanical model of the eye after glaucoma surgery, in
terms of tissue properties and fluid drainage. This model was informed by experimental data and clinical
observations, and describes what is happening to a healing eye. We have used this model to predict the impact
of hydrostatic forces at the wound site and determine some ideal parameters for a drainage operation. This
knowledge has enabled us to begin developing and testing new glaucoma drainage devices., , Additionally we
developed a new method for assessing how drainage operations function in the rabbit, which may improve the
clinical relevance of future work using animal models of glaucoma surgery. The new method provides a way to
directly measure how the surgically-created filtration pathway is working, isolated from the confounding
effects of fluid dynamics elsewhere in the eye., , We also found that a monoclonal antibody targeting Vascular
Endothelial Growth Factor (VEGF) displayed antifibrotic effects in cell culture and rabbit models, potentially
leading to another target for modulation of wound healing after glaucoma surgery.,
Expected future outcomes:
, It is anticipated that the ideal physical parameters identified using this study's experimental and computational
models will lead to the development of new drainage devices and surgical techniques for glaucoma surgery. In
conjunction to existing anti-scarring treatments this could increase the long term success of filtration
operations.
Name of contact:
Professor Jonathan Crowston
Email/Phone no. of contact:
crowston@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 229011
Start Year: 2003
CIA Name: Prof Leon Straker
End Year: 2005
Admin Inst: Curtin University of Technology
Grant Type: NHMRC Project Grants
Main RFCD: Environmental and Occupational Health and Safety
Total funding: $207,353
Title of research award:
Biomechanical and physiological responses of children and young adults to different computer
workstationsBiomechanical and physiological responses of children and young adults to different computer
workstations
Lay Description (from application):
Computer use is increasing with 95% of Australian primary school children now using computers. Two out of
three children and three out of four adult workers report pain associated with computer use. This has lead to
concerns that increased computer use may be responsible for an increase in musculoskeletal disorders in young
people. Little is known about the physical consequences of children's use of computers. The information we
have on adult use is now out of date because of changes to computer technology and how computers are used.
It is therefore not possible to provide evidence-based recommendations for safe use of computers by young
people. Critical gaps in our knowledge include the appropriate desk design and computer display position. The
proposed studies will use recent advances in biomechanical and physiological measurement and modelling of
musculoskeletal stress to evaluate a range of desk designs and computer display positions for young adults,
preadolescentchilden and early school age children. The outcomes will include the first detailed description of
the physical stresses of computer use by children and preliminary guidelines for workstation design.
Research achievements (from final report):
Computer use by young Australians is becoming ubiquitous. This project provided the first detailed description
of the physical impact of workstation design features when young children (5-6years), pre-adolescents (1012years) and young adults (18-25years) worked with computers and with paper based technology. The project
pioneered the use of new measures of stress on the neck and shoulder which accounted for the variation in
posture and muscle activity. Variation is thought to be important for preventing the development of pain. The
project was the first to describe the posture of computer users in three dimensions. The project also pioneered
the use of complex biomechanical models to investigate the stress on muscles deep in the neck which are
difficult to access for direct measurement. Providing forearm support during computer work was found to
decrease the stress on the neck and shoulders. Positioning a computer display very high or very low was found
to increase the stress on parts of the neck and shoulders. Using tablet computers was found to be similar to
working with books and paper. The use of new measures of physical stress provided new insights into why
neck pain is so common in computer users. The knowledge gained from this project is the most comprehensive
available and will guide the development of evidence based guidelines for wise use of computers by young
people.
Expected future outcomes:
We are expecting our research to be the benchmark for future research into the physical impact of computer use
by children. We are also expecting the guidelines we develop based on this project to be widely used by
education authorities and parents worldwide.
Name of contact:
Professor Leon Straker
Email/Phone no. of contact:
L.Straker@curtin.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 323200
Start Year: 2005
CIA Name: Prof Leon Straker
End Year: 2008
Admin Inst: Curtin University of Technology
Grant Type: NHMRC Project Grants
Main RFCD: Clinical Sciences not elsewhere classified
Total funding: $682,800
Title of research award:
Physical, lifestyle and psychosocial determinants of spinal pain development in adolescentsPhysical, lifestyle
and psychosocial determinants of spinal pain development in adolescents
Lay Description (from application):
This project aims to understand the development of back and neck pain in adolescence. By the age of 16
around half of all adolescents have suffered back pain and one third have suffered neck pain. For many
adolescents this pain is disabling and over a third of sufferers miss school, miss recreation and seek medical
help. The current understanding of back and neck pain in adolescence is quite limited - restricting the
effectiveness of initiatives to prevent adolescents having to suffer spinal pain and of treatment of those
adolescents unlucky enough to have an episode. Better understanding and interventions for adolescent spinal
pain will also have longer term implications by reducing adult spinal pain. Four out of 5 adults will experience
spinal pain. In the USA treating adult back pain is the 4th largest health care cost. Many adults with chronic
back pain had their first episode during adolescence. A better understanding of spinal pain in adolescence may
help prevent it developing into a lifelong disability. We will collect information from 2,000 adolescents on
their experience of back and neck pain and on potential physical, lifestyle and psychosocial risk factors. We
believe factors such as their posture, muscle capacity, TV and computer use, mental health and social situation
all combine to influence whether a person develops back or neck pain. The project is unique as it will not only
collect a broad range of information during adolescence, but will also make use of a large database of health,
developmental and psychosocial information already collected from these children since birth.With a better
understanding of the development of spinal pain we will be able to develop guidelines to help prevent these
problems. We will also be able to develop better treatment plans for sub-groups of adolescents with a particular
combination of risk factors. Together these initiatives will assist in understanding and breaking the pathway to
chronic spinal pain.
Research achievements (from final report):
This project funded the collection and partial analysis of information about back and neck pain in adolescents
at 14 and 17 years in the Raine pregnancy cohort study. Spinal pain was found to be already common at 14
years of age and to already be associated with disability at 17 years of age. Information on a wide range of
physical, lifestyle and psychosocial risk factors was also collected. Posture, fitness, obesity, motor competence,
physical activity, computer use, school bag carriage, diet, smoking and alcohol use, depression, externalising
behaviours, self worth, parental pain experience, socioeconomic status, family functioning and life stress
events were all related to spinal pain. Subgroups of individuals with spinal pain were also identified suggesting
interventions could be targetted. The findings refuted a common misperception that adolescent spinal pain is
trivial. They also suggested windows for interventions to reduce spinal pain risk (early life and adolescence)
and arrest a trajectory to chronic, disabling adult spinal pain. Grant applications have been submitted to follow
this cohort into early adulthood.
Expected future outcomes:
The publiction of the results of this project will correct a misperception about the importance of adolescent
spinal pain. We have identified several opportunities to reduce risks and will apply for funding to assess the
efficacy of targetting specific interventions.
Name of contact:
Professor Leon Straker
Email/Phone no. of contact:
L.Straker@curtin.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 350992
CIA Name: A/Pr Tony Butler
Admin Inst: Curtin University of Technology
Main RFCD: Epidemiology
Total funding: $453,500
Start Year: 2005
End Year: 2009
Grant Type: Career Development Fellowships
Title of research award:
Improving and monitoring the health of prisoners in AustraliaImproving and monitoring the health of prisoners
in Australia
Lay Description (from application):
Not Available
Research achievements (from final report):
This award enabled me to pursue a broad range of research activities in regard to offender health leading to a
range of positive outcomes for this population. For example, Australia is now the only jurisdiction to collect
national health indicators for prisoners' health and the only jurisdiction worldwide to have implemented
ongoing national surveillance of bloodborne viruses and sexually transmitted infections. Work on establishing
both these project were possible due to the CDA. Other project have been pursued in other areas including
mental health, violence and tobacco smoking.
Expected future outcomes:
As a result of the CDA and the body of work attached to it, I was awarded a Future Fellowship in 2009 to
continue my work. The next evolution for this area is to establish a national offender health research centre.
Name of contact:
Tony Butler
Email/Phone no. of contact:
tbutler@nchecr.unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 373638
CIA Name: Dr Anne Smith
Admin Inst: Curtin University of Technology
Main RFCD: Applied Statistics
Total funding: $138,375
Start Year: 2006
End Year: 2009
Grant Type: Early Career Fellowships (Australia)
Title of research award:
Characterisation of subgroups of adolescent low back pain & preventable determinants: advanced statistical
approaches...Characterisation of subgroups of adolescent low back pain & preventable determinants: advanced
statistical approaches...
Lay Description (from application):
Not Available
Research achievements (from final report):
This fellowship funded analysis of data about spinal pain in adolescents at 14 and 17 years in the Raine
pregnancy cohort study. The experience of spinal pain was found to be already common at 14 years, and to
have significant impact on a subgroup of adolescents by 17 years. The association of point and/or trajectory
measures of a wide range of physical, lifestyle and psychosocial risk factors with spinal pain and impact were
established. Subgroups of adolescence with spinal pain were identified for which preventation and management
could be targetted. The results suggest early and targetted prevention and management of spinal pain and
disability is relevant and achievable. Grant applications have been submitted to follow this cohort into
adulthood., This fellowship also funded other projects identifying early and modifiable risk factors for pain and
disability in young athletes, musicians and nurses.
Expected future outcomes:
Several opportunities for early intervention in childhood and adolescence to reduce the burden of chronic
spinal pain have been identified by this research, and we will apply for funding to assess the efficacy of
targetted interventions.
Name of contact:
Anne Smith
Email/Phone no. of contact:
Anne.Smith@curtin.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 425550
Start Year: 2007
CIA Name: Dr Andrew Briggs
End Year: 2013
Admin Inst: Curtin University of Technology
Grant Type: Early Career Fellowships (Australia)
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $198,533
Title of research award:
Understanding thoracic spine pain in adolescence and adulthoodUnderstanding thoracic spine pain in
adolescence and adulthood
Lay Description (from application):
Not Available
Research achievements (from final report):
This funding provided the Fellow with the opportunity to undertake novel and innovate clinical and policydriven research into musculoskeletal health in Australia. Broadly, five areas of work were covered over the
funding period, including:, o
Epidemiologic research into spinal
pain, particularly mid-back pain, in children, adolescents and working adults. Through systematic reviews,
important data were collated and synthesised to describe the impact of this spinal pain condition. These data
complement other data in emphasising the significance of spinal pain conditions., o
Clinical research
examining the negative effects of low back pain on skeletal health, particularly bone mineral density in the low
back. Preliminary data were acquired to demonstrate the association between low back pain and reduced low
bone mineral density., o
Clinical research examining
musculoskeletal health within families in WA. A novel familial study was undertaken to examine the familial
links in musculoskeletal health, such as posture, low back pain, beliefs and muscle strength. The same family
cohort was used to examine health literacy among adults in WA., o
Continued development and
feasibility testing of a novel method to measure bone mineral density (BMD) in the lumbar spine. While
standard techniques for measuring BMD rely on estimating average BMD within a vertebral body, our novel
method enables the user to measure BMD within vertebral subregions. Emerging data suggest the method is
better able to identify individuals with and without osteoporotic fractures. Ultimately, the method may be used
in clinical practice to better identify individuals at risk of vertebral fracture., o
Partnershipdriven research between policy, clinical and academic domains to evaluate the implementation of the Western
Australian Models of Care for musculoskeletal health.
Expected future outcomes:
Future outcomes fall within two categories:, o
Innovation: further development and
application of novel methods to measure bone mineral density in clinical setting to better identify individuals at
risk of fracture., o
Expansion of partnership-driven
research between policy makers, clinicians, and academics in the implementation of health policy.
Name of contact:
Dr Andrew Briggs
Email/Phone no. of contact:
A.Briggs@curtin.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 533502
Start Year: 2009
CIA Name: Prof James Semmens
End Year: 2011
Admin Inst: Curtin University of Technology
Grant Type: NHMRC Project Grants
Main RFCD: Public Health and Health Services not elsewhere classified
Total funding: $404,579
Title of research award:
The epidemiology, healthcare utilisation, treatment pathways and patient outcomes for burn injuries in Western
AustraliaThe epidemiology, healthcare utilisation, treatment pathways and patient outcomes for burn injuries in
Western Australia
Lay Description (from application):
The aims of this research proposal are to investigate the patterns of burn injury, health service utilisation,
economic costs, treatment pathways, and outcomes for all patients hospitalized with burn injury in Western
Australia for the period 1999-2008. An important focus will also be on the developing preventative injury
education strategies. The proposal outlines a new collaborative initiative between the Burn Service of WA and
the WA Centre for Population Health Research at Curtin University.
Research achievements (from final report):
This study involved collaboration between burns specialists, epidemiologists, health economists and health
researchers to provide a unique clinical research program to support burns research. The project assessed the
clinical epidemiology, health service utilisation, economic costs, treatment pathways and outcomes for all
patients hospitalised with burn injury in WA for the period 1980-2008. The project contributed : 1) estimated
the crude and relative annual hospital admission and mortality rates for burn injury in Western Australia 19802008; 2) evaluated the health utilisation patterns for burn patients during the index burn admission; 3)
measured the crude and relative longitudinal patterns of health care events and health outcomes encountered by
patients during the long-term management of their burn injury; 4) estimated the economic cost of the intensive
resource utilisation associated with acute and long term burn injury management; 5) disseminated outcomes to
inform prevention programs, treatment pathways, disaster response and education all have direct community
impact., The project examined trends in burns injury and important outcomes resulting from burns for obsteric
outcomes, cancer outcomes, rural versus remote injuries and age related injuries. The project produced 8
scientific papers and 10 conference presentations.
Expected future outcomes:
The project has led to the establishment of the WA Burns Research Centre, based at the Unversity of Western
Australia and led by Professor fiona Wood. The research project has also provided the opportunity for
international comparison in Scotland ( the Scottish Information Services Division), Oxfor University (through
the Oxford Record Linkiage Unit, and the Swansea Data Linkage Unit (Wales, UK).
Name of contact:
Professor Fiona Wood
Email/Phone no. of contact:
Fiona Wood <fw@mccomb.org.au>
NHMRC Research Achievements - SUMMARY
Grant ID: 533504
CIA Name: Prof Tony Butler
Admin Inst: Curtin University of Technology
Main RFCD: Preventive Medicine
Total funding: $275,401
Start Year: 2009
End Year: 2012
Grant Type: NHMRC Project Grants
Title of research award:
Does Traumatic Brain Injury lead to offending behaviour?Does Traumatic Brain Injury lead to offending
behaviour?
Lay Description (from application):
Rates of reported traumatic brain injury (TBI) in offender and prisoner populations are extremely high (~80%).
It has been suggested that TBI may be responsible for half the crimes leading to incarceration. Criminal
behaviour is complex and the role of TBI in this conundrum is unclear. Our study will examine this question
using data-linkage. Should we find a link between TBI and subsequent offending, this opens up the possibility
of developing interventions aimed at preventing this trajectory.
Research achievements (from final report):
This study has demonstrated that the link between exposure to traumatic brain injury and subsequent offending
behaviour is not a simple exposure and outcome relationship as many have assumed. What we demonstrated
through the careful selection of community and sibling controls is that while exposure to traumatic brain injury
is indeed associated with an increased risk of offending behaviours, when we examined sibling controls this
relationship does bear out. Thus, in logistic regression models adjusted for treatment for drug or alcohol abuse,
psychiatric illness, Aboriginality, and socioeconomic disadvantage, TBI was associated with increased
offending in both males (OR =1.7, 95% CI 1.5-1.9) and females (OR=1.5, 95% CI 1.2-1.9) compared with the
unexposed community group. However, when compared with unexposed siblings, no association between TBI
and offending was apparent in either sex (males OR = 1.1, 95% CI 0.9-1.3; and females OR = 0.9, 95% CI 0.61.2)., The results of this study do not support the hypothesis that TBI significantly increases the risk of
subsequent offending. The lack of an association between TBI and offending when siblings served as a
comparison group suggests that the risks both of offending and TBI may be influenced by common genetic,
familial and developmental factors.
Expected future outcomes:
We anticipate that future research will focus on the risk of offending in those exposed to traumatic brain injury
but will not view this in a simplistic cause and effect relationship.
Name of contact:
Tony Butler
Email/Phone no. of contact:
tbutler@kirby.unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 533526
Start Year: 2009
CIA Name: Prof Leon Straker
End Year: 2012
Admin Inst: Curtin University of Technology
Grant Type: NHMRC Project Grants
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $538,136
Title of research award:
RCT of the impact of electronic game use by children on physical activity and energy expenditureRCT of the
impact of electronic game use by children on physical activity and energy expenditure
Lay Description (from application):
Increasing childhood obesity and reduced physical activity are major health issues in Australia. Three quarters
of Australian children play electronic games and this is widely thought to reduce their physical activity. Whilst
the effect of TV viewing is well understood, the impact of electronic games is not. This study will test whether
access to electronic games results in decreased physical activity in children. We need to understand the impact
this popular activity is having on child health.
Research achievements (from final report):
Data successfully collected from 87 families enabling testing for the first time the relative benefit of banning or
replacing sedentary electronic games.
Expected future outcomes:
Advice for health practitioners, educators and parents on whether banning electronic games or replacing
sedentary electronic games with active electronic games results in better activity outcomes., Advice to gaming
industry on desirable features of electronic games
Name of contact:
Leon Straker
Email/Phone no. of contact:
L.Straker@curtin.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 534409
CIA Name: Prof Robert Newton
Admin Inst: Edith Cowan University
Main RFCD: Oncology and Carcinogenesis
Total funding: $519,331
Start Year: 2009
End Year: 2012
Grant Type: NHMRC Project Grants
Title of research award:
A Phase III clinical trial of exercise modalities on treatment side-effects in men receiving therapy for prostate
cancerA Phase III clinical trial of exercise modalities on treatment side-effects in men receiving therapy for
prostate cancer
Lay Description (from application):
Hormone therapy is very effective for treating prostate cancer however it produces a number of side effects
including muscle and bone loss, fat gain, and increased risk of death from heart disease and diabetes. In other
populations physical exercise has proven particulary effective for preventing such problems however no long
term studies with prostate cancer patients have ever confirmed this. Knowledge gained from this study has
potential to markedly reduce suffering and increase survival.
Research achievements (from final report):
This randomised controlled trial of different exercise modes is the longest and largest ever completed in men
with prostate cancer to our knowledge. With the primary outcome being bone mineral density it is also one of
the first to address bone loss as a devastating toxicity of androgen deprivation therapy. A particularly unique
feature of this project was the application of "impact" exercise as highly tailored and specific prescription to
slow or possibly prevent bone loss resulting from testosterone suppression. We observed for the first time that
exercise could totally prevent bone loss in men receiving androgen deprivation therapy while men receiving
usual care continued to exhibit declines in bone mineral density. Importantly in terms of current national and
international exercise recommendations a more standard exercise program consisting of aerobic and resistance
training did not appreciably slow bone loss in these patients. This was surprising given previous research
findings in men and women not receiving testosterone suppression received considerable benefit in terms of
bone health from such a standard program. In terms of muscle mass the combination of impact and resistance
training produced significantly greater gains in terms of muscle hypertrophy than the standard program and
usual care resulted in continuing muscle atrophy. This is also a novel finding as it appears that men with
prostate cancer undergoing testosterone deprivation appear much more susceptible to the interference effects of
aerobic exercise undertaken simultaneously with resistance exercise.
Expected future outcomes:
Exercise prescription for cancer patients appears to require much more specific attention to exercise mode and
dosage, in particular if treatment side-effects are to be prioritised for management. The principal future
outcome of this research should be the change to clinical practice with tailored exercise programs rather than
provision of current generic guidelines.
Name of contact:
Professor Rob Newton
Email/Phone no. of contact:
r.newton@ecu.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 160052
CIA Name: A/Pr Xin-Fu Zhou
Admin Inst: Flinders University
Main RFCD: Cellular Nervous System
Total funding: $461,443
Start Year: 2001
End Year: 2005
Grant Type: NHMRC Project Grants
Title of research award:
Roles of brain-derived neurotrophic factor in plasticity of injured sensory neuronsRoles of brain-derived
neurotrophic factor in plasticity of injured sensory neurons
Lay Description (from application):
The fundamental problem of how nerve cells respond to a nerve injury has long been studied by neuroscientists
and clinicians. After a nerve injury outside the brain or spinal cord, ie, in the periphery, some sensory nerve
cells die, some regenerate to reconnect to their targets, and some sprout to make abnormal connections. Recent
evidence from our lab and others indicates that the nerve sprouting is linked to chronic pain experienced by
nerve-injury patients. However, how these changes occur still remains largely unknown. Our recent studies
showed that growth factors, particularly brain-derived neurotrophic factor (BDNF) which is made by the
sensory nerve cells, may play important roles in mediating these changes. This proposed project, directly
evolved from our recent exciting findings, aims to further examine roles and action mechanisms of BDNF and
its relatives in regulating the responses of sensory nerve cells to a nerve injury. We propose that after an injury,
BDNF promotes survival of some nerve cells, enhances sensory nerve regeneration in both periphery and
spinal cord, and also mediates abnormal nerve sprouting and is involved in neuropathic pain. With strong
expertise and powerful tools in hand, we have designed a series of experiments to investigate the roles and
action mechanisms of BDNF and its related molecules in these processes. Results from this project will help
us understand mechanisms underlying the responses of nerve cells to a nerve injury, and should provide much
needed information which would help in designing new methods for enhancing nerve cell survival and nerve
regeneration as well as for inhibiting nerve injury-induced chronic pain in nerve-injury patients.
Research achievements (from final report):
This project grant enable us to investigate the functional roles of brain derived neurotrophic factor and nerve
growth factor in the development of neuropathic pain, in the regeneration of injured spinal cord and nerve cell
death after nerve injury. We found that after nerve injury neuropathic pain is partially caused increased
production of neurotrophic factors. Suppression of these factors with specific antibodies can alleviate the pain.
We found that the neuropathic pain is caused by inflammation but not direct damage to sensory nerves. We
also found that increased production of neurotrophic factors plays a critical role in the regeneration of injured
cord. These factors can either protect nerve from death or enhance the death depending the microenvironment
and expression levels of their receptor p75.
Expected future outcomes:
Based on our findings, we can develop therapeutics for the treatment of neuropathic pain by using antagonizing
drugs to nerve growth factor or brain derived neurotrophic factor. We may also increase the production of
BDNF by the peripheral nerves or tissues to enhance the regeneration of the spinal cord.
Name of contact:
Xin-Fu Zhou
Email/Phone no. of contact:
xin-fu.zhou@flinders.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 160062
CIA Name: Prof Jegan Krishnan
Admin Inst: Flinders University
Main RFCD: Orthopaedics
Total funding: $188,450
Start Year: 2001
End Year: 2003
Grant Type: NHMRC Project Grants
Title of research award:
The design, development and clinical assessment of a new metacarpophalangeal joint prosthesisThe design,
development and clinical assessment of a new metacarpophalangeal joint prosthesis
Lay Description (from application):
Rheumatoid arthritis is a crippling form of arthritis that affects many people in the community. It commonly
involves the finger joints in the hands resulting in deformity, pain and subsequent loss of function. There have
been implants designed for finger joint replacement, but unfortunately these implants have had only moderate
benefits and can break and lead to further joint destruction resulting in the worsening of deformity and pain. A
new implant for finger joint replacement has been developed. This implant has several potential advantages.
Firstly the unique design acts to prevent recurring deformity in the fingers with rheumatoid disease while
allowing functional motion. Secondly, it is thought that patients will return to function earlier and avoid the
need for further finger surgery as this implant design relies less on the tissues around it for stability. The
purpose of this study is to investigate the biomechanical and clinical benefits of this new implant for finger
joint replacement. The new design will undergo specific laboratory tests and be used in a clinical trial to
quantify the therapeutic benefits it provides to patients with rheumatoid arthritis.
Research achievements (from final report):
The reseach in the project assessed a newly developed implant for knuckle joint replacement. This joint was
tested biomechanically and manufacturing processes and the materials used to make the implant were refined
accordingly. Subsequent implant of this new joint into a person with rheumatoid arthritis showed that the joint
was effective in restoring function to the hand. One very important observation from this research was that the
tools available to assess hand function were limited, particularly for people with rheumatoid arthritis before and
after joint-replacement surgery. Therefore, considerable effort was made to improve and standardise the
available tools and to develop new and more appropriate tools and measurement devices.
Expected future outcomes:
Commercial development of the newly developed prosthesis is continuing with an Orthopaedic prosthesis
manufacturer., The development and assessment of hand-function testing tools and devices is also expected to
lead to new instruments more appropriate to the rheumatoid hand.
Name of contact:
Professor Jegan Krishnan
Email/Phone no. of contact:
jegan.krishnan@flinders.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 160091
CIA Name: A/Pr John Wakerman
Admin Inst: Flinders University
Main RFCD: Not Allocated
Total funding: $215,299
Start Year: 2001
End Year: 2005
Grant Type: SRDC - Research
Title of research award:
Injury Prevention through Community Development Initiatives in Central AustraliaInjury Prevention through
Community Development Initiatives in Central Australia
Lay Description (from application):
Not Available
Research achievements (from final report):
The study has provided a detailed description and analysis of injury in Central Australia. Analysis of
hospitalisations and deaths due to injury show very high rates in the region, particularly in the Aboriginal
population. Land transport accidents were the most common cause of injury deaths for all residents of Central
Australia, accounting for 36% of all injury deaths. For Aboriginal residents, homicide and suicide followed
with similar rates, whereas for non-Aboriginal residents suicide was the second highest cause of injury death,
followed by falls. Assault and other interpersonal violence were by far the most common external cause of
hospitalised injury of Aboriginal residents of Central Australia, accounting for about 47% of episodes.
Complications of care and falls were other common categories of external causes of injury for Aboriginal
residents. Falls and land transport crashes were the most common external causes of hospitalised injury for
other residents. There is a very recent history of systematic racism and external injury to Aboriginal people in
the region. This includes the Stolen Generation and physical exclusion of Aboriginal people. Aboriginal
perceptions of injury were much broader than the standard public health definition of external injury.
Aboriginal people also describe a linked concept of 'inside injury' - a psychological or spiritual harm that can
be caused by denial of culture or Aboriginal law, racism, failure to acknowledge or support Aboriginal
initiative, poor communication of health or criminal justice information, sorcery, alcohol and other drugs.
Tangentyere Council is at the forefront of injury prevention. Its Night Patrol and Wardens Program were
evaluated and found to be effective Aboriginal initiatives based on Aboriginal systems of knowledge. They
address both downstream factors (keeping people out of the criminal justice system) and upstream factors
(empowering both the organisation and individuals) in injury prevention.
Expected future outcomes:
A number of potential benefits arise from this study.Thy include improvements in communication from the
health and criminal justice systems; development of a regional public transport system to remote communities;
strengthening of the Tangentyere Night Patrol; further research into the economic benefits of the Night Patrol
and the concept of 'inside injury'; improvements in injury data collection.
Name of contact:
John Wakerman
Email/Phone no. of contact:
john.wakerman@flinders.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 229980
CIA Name: Prof Trevor Hearn
Admin Inst: Flinders University
Main RFCD: Not Allocated
Total funding: $470,000
Start Year: 2003
End Year: 2006
Grant Type: NHMRC Development Grants
Title of research award:
Effects of pin biomechanics, coating material and surface roughness on the pin-bone interface in external
repairEffects of pin biomechanics, coating material and surface roughness on the pin-bone interface in external
repair
Lay Description (from application):
Some fractures require external fixation, anchored with metal pins in the bone fragments. The reatment is
generally successful, although the pin tracts often loosen and become infected. This complication may
jeopardise fracture healing and must be treated. The purpose of this project is to determine what aspects of pin
design predispose to these problems at the pin-bone interface. Is it the way the pins are initially inserted,
perhaps not tightly enough so that the pin is unstable, or perhaps too tight, causing microcracks in the bone? Is
it the material of the pin, which might be improved with a bioactive coating? Is it the surface roughness which
causes different responses of bone cells? Would it help to have an antibiotic pin? This proposal is designed to
answer these questions. The biomechanics of the pin will first be studied with computer models and then tested
in the laboratory. The loosening and infection associated with different types of pin will then be studied
biologically. The results of the study will clarify the roles of pin biomechanics, coating and surface roughness,
leading to improvements in design and better outcomes in fracture patients.
Research achievements (from final report):
This project has established the foundations for a new device for the fixation of common fractures of the wrist.
Curently used fixation pins have had a high rate of infection and loosening, with instability of the pin-bone
interface as the primary precursor. The new design will optimize the stability of this interface over the time
course of fracture repair.
Expected future outcomes:
Increasing the stability of this interface will reduce infection rates and decrease need for further medical care.
Name of contact:
Prof Trevor C Hearn
Email/Phone no. of contact:
tnahearn@ozemail.com.au
NHMRC Research Achievements - SUMMARY
Grant ID: 375100
CIA Name: A/Pr Judith Morris
Admin Inst: Flinders University
Main RFCD: Autonomic Nervous System
Total funding: $472,771
Start Year: 2006
End Year: 2008
Grant Type: NHMRC Project Grants
Title of research award:
Neural circuits producing pelvic vasodilation in femalesNeural circuits producing pelvic vasodilation in
females
Lay Description (from application):
The reproductive organs and genitalia in males and females experience a large increase in blood flow during
sexual and reproductive activity. This increased blood flow (vasodilation) is a key component of penile and
clitoral erection, and enhances secretion from the lining of the internal reproductive organs. Vasodilation
during sexual activity is produced by a special sets of nerves receiving signals from the genitalia and the brain.
In fact, Viagra works by enhancing and prolonging the actions of these nerves. An important part of this neural
pathway is a group of nerve cells in the spinal cord that connects the central nervous system with peripheral
nerves in the reproductive organs - these are called preganglionic neurons. Recently we discovered that a major
pathway from the spinal cord to the pelvic blood vessels in females leaves the spinal cord at a different level
(lumbar) from that thought previously (sacral level). Currently there is no information on how these lumbar
preganglionic nerves in females are connected to other nerve pathways that are active during sexual activity,
and how they integrate signals from both the internal organs and the brain. We will use an array of modern
cellular techniques together with direct observation of dilation in isolated uterine arteries to discover how these
nerve cells are wired up in circuits in the spinal cord. This information is vital for us to understand the factors
producing increased blood flow in normal sexual activity, and how these might be altered in inflammation or in
conditions where there could be selective damage to one nerve pathway and not the other, such as after pelvic
surgery, spinal cord damage at different levels, or stimulation of the spinal cord for treatment of chronic pain.
Our study also will help understand referred pain and sensations of discomfort in abdominal and pelvic organs.
Research achievements (from final report):
We studied the nerve pathways that are important for increasing blood flow to the female reproductive organs
during sexual activity and the early stages of pregnancy. Using newly developed animal models we showed
that a previously under-recognised nerve pathway leaving the lumbar spinal cord and descending to the
reproductive organs can be activated by artificial stimulation of nerves from the genital region. However, we
found that this new pathway is normally inhibited by other nerves within the spinal cord during genital
stimulation. It is unclear at the moment how much this new pathway contributes to increased blood flow during
normal sexual activity when other nerve pathways at sacral spinal levels are also activated. However, our
results indicate that the lumbar nerve pathway is likely to be very important under conditions where the sacral
nerves are damaged after essential surgery or low level spinal cord injury. This pathway is also likely to be
involved in some sorts of pelvic pain, and may help to explain sexual and reproductive dysfunction during
chronic inflammatory conditions. As the lumbar pathway has not been widely recognised in previous medical
research and clinical practice, our results present a shift in thinking about neural regulation of the reproductive
organs in health and disease.
Expected future outcomes:
This study should stimulate new research directions and promote use of our animal models to complement data
from current research. Once the significance of our findings have been clarified in animal studies it is likely
that they will impact on surgical and medical practice addressing a range of women's health issues.
Name of contact:
Prof Ian Gibbins
Email/Phone no. of contact:
Ian.Gibbins@flinders.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 375109
CIA Name: A/Pr Xin-Fu Zhou
Admin Inst: Flinders University
Main RFCD: Central Nervous System
Total funding: $472,771
Start Year: 2006
End Year: 2008
Grant Type: NHMRC Project Grants
Title of research award:
Roles of peripherally derived BDNF in regeneration of spinal cord and the mechanismsRoles of peripherally
derived BDNF in regeneration of spinal cord and the mechanisms
Lay Description (from application):
Injury to the brain and spinal cord often leads to permanent disability due to lack of regeneration. The
mechanism why central nerve does not regenerate is not known. Neurotrophic factors are powerful molecules
which can overcome effects of inhibitory factors on regeneration. This project aims to investigate how
neurotrophic factors override the effects of inhibitory factors and how to improve the regeneration by
increasing the production of neurotrophic factors within nerves. Successful completion of this project will help
understanding the mechanism of how neurotrophic factors work on regeneration and developing the effective
way to improve regeneration of the injured spinal cord.
Research achievements (from final report):
We found that peripheral nerve lesion induced down-regulation of p75NTR and upregulation in satellite glia
but spinal cord lesion caused upregulation of p75 in sensory neurons. We showed that 85% of regenerating Fast
Blue labelled neurons did not express p75NTR but were surrounded by p75NTR+ satellite glia. , We also
investigated the relationship between BDNF expression in DRG and regenerating neurons after spinal cord
injury with a prior conditioning lesion of sciatic nerve. We found that majority of regenerating neurons were
positive for BDNF and for trkC. We found that injection of exogenous BDNF into the sciatic nerve or into the
footpad promoted the regeneration of ascending sensory neurons after spinal cord injury. This work suggests
for the first time that peripherally derived BDNF may promote the regeneration of the spinal cord. , Sciatic
nerve lesion triggered upregulation of BDNF in the injured spinal cord and in other systemic tissues such as the
pituitary gland. The enhanced regeneration of corticospinal neurons was blocked by antibodies to BDNF,
suggesting the peripherally derived BDNF may play a role in the regeneration.
Expected future outcomes:
We now expect that with the support of a commercial company we can expore the use of BDNF by peripheral
injection to promote regeneration of the injured spinal cord and to carry a clinical trial for the application of
BDNF in patients.
Name of contact:
Xin-Fu Zhou
Email/Phone no. of contact:
zhou0010@flinders.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 375123
CIA Name: Dr Vladimir Zagorodnyuk
Admin Inst: Flinders University
Main RFCD: Nephrology and Urology
Total funding: $408,862
Start Year: 2006
End Year: 2008
Grant Type: NHMRC Project Grants
Title of research award:
Sensory mechanisms in normal bladder and in cystitisSensory mechanisms in normal bladder and in cystitis
Lay Description (from application):
The function of the lower urinary tract is to store urine and release it at appropriate times. This requires neural
circuits in the brain, spinal cord and peripheral ganglia. When the bladder fills, sensory neurones fire and
activate these neural circuits to store urine or to empty the bladder. If sensory neurones are too easily excited
(a process called sensitisation ) this will lead to clinical disorders, including the common painful bladder
syndromes, whose cause is not known (interstitial cystitis, sensory urgency etc). These are characterised by
pelvic pain, urinary urgency, frequency and, in some cases, urge incontinence (loss of urine for no apparent
reason) which results from unstable or overactive bladder. Despite a large database of knowledge about the
sensory innervation of the bladder, many important gaps still exist. These gaps have restricted the development
of new therapies. For example, we have little idea about exactly which functional classes of sensory neurones
signal filling of the normal bladder or what different types of information they carry. This is vital information
for understanding which neurones are affected in disease states and whether they are all affected in the same
way. We have developed new methods that will allow us to identify the major classes of sensory neurones that
innervate the bladder, what they respond to and how they are activated. We will also determine whether some
classes are preferentially sensitised by inflammation and the most important mechanisms that are likely to
underlie this. The significance of this project is that it provides the basic scientific understanding of sensory
innervation of the bladder and will identify potential targets for selective pharmacological intervention in
common bladder disorders.
Research achievements (from final report):
The major achievements of the project are the identification and characterization of five distinct classes of
extrinsic sensory neurones to the bladder which have different physiological and pathophysiological roles.
These include two stretch-sensitive afferents (muscle mechanoreceptors and muscle-mucosal
mechanoreceptors), and three stretch-insensitive afferents (mucosal high and low-responding
mechanoreceptors and high threshold vascular mechanoreceptors). Transduction by major classes of bladder
afferents does not depend upon Ca2+-sensitive exocytotic release of mediators, or endogenous release of ATP.
Rather, benzamil-sensitive stretch-activated ion channels are present on their mechanosensitive endings and are
involved in direct mechanotransduction. Different classes of bladder afferents have distinct chemosensitivity to
agonists and noxious agents. It is likely that two classes of capsaicin-sensitive afferents, mucosal highresponding mechanoreceptors and high threshold vascular mechanoreceptors, are potential nociceptors and
targets for pharmacological intervention in common bladder disorders. Discovery of TTX-resistant
spontaneous release of acetylcholine from autonomic cholinergic extrinsic and intrinsic nerves which affects
bladder contractility is also important in defining new strategies for the treatment of the overactive bladder
syndrome.
Expected future outcomes:
This research is likely to lead to significant basic science advances in the field of autonomic neuroscience and
will be beneficial for developing new targets for parmacological treatment of common bladder disorders.
Name of contact:
Vladimir Zagorodnyuk
Email/Phone no. of contact:
vladimir.zagorodnyuk@flinders.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 375196
Start Year: 2007
CIA Name: Prof Fran Baum
End Year: 2012
Admin Inst: Flinders University
Grant Type: NHMRC Strategic Awards
Main RFCD: Public Health and Health Services not elsewhere classified
Total funding: $1,140,343
Title of research award:
Changing patterns of work: impacts on physical and mental health and the meditating role of resiliency and
social capitalChanging patterns of work: impacts on physical and mental health and the meditating role of
resiliency and social capital
Lay Description (from application):
This project will provide, for the first time in Australia, a detailed understanding of the impact of the changing
forms of employment and unemployment on overall health. It will provide original insights into what aspects
of the employment relation help or harm health, and on what enables some people to escape the harm that
others experience. This will provide vital information to underpin policies designed to gain the benefits of a
flexible workplace, with minimum harm to workers.
Research achievements (from final report):
This project provided, for the first time in Australia, a detailed understanding of the impact of the changing
forms of employment and unemployment on overall health. It provided original insights into what aspects of
the employment relation help or harm health; and what enables some people to escape the harm that others
experience. It has provided vital information to underpin policies designed to gain the benefits of a flexible
workplace, with minimum harm to workers.
Expected future outcomes:
This research has informed future research programs of the National Institute of Labor Studies at FUSA and
encouraged them to add health considerations to their work. It also led to a program on work, health and social
capital at the Southgate Institute, which will continue to publish in the area.
Name of contact:
Professor Fran Baum
Email/Phone no. of contact:
fran.baum@flinders.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 426750
CIA Name: Prof Ian Gibbins
Admin Inst: Flinders University
Main RFCD: Sensory Systems
Total funding: $499,860
Start Year: 2007
End Year: 2009
Grant Type: NHMRC Project Grants
Title of research award:
Synaptic environment of nociceptive inputs to the spinal cordSynaptic environment of nociceptive inputs to the
spinal cord
Lay Description (from application):
Pain affects everyone at some stage in their life. Usually, the pain subsides by itself as the underlying cause is
resolved. Thus, the damaged tissue heals or we move away from a potentially injurious stimulus and we
become free of pain. However, pain can persist for two main reasons: the underlying cause cannot be treated
adequately and the painful stimulus continues; or the pain is maintained long after the primary stimulus has
resolved. This ongoing pain often is resistant to alleviation by common analgesics. Therefore, a major aim of
the pharmaceutical industry is the development of new drugs to target persistent pain. This requires a thorough
understanding of how the nerves that detect painful stimuli transmit that information into the spinal cord, and
then on to the brain, where we construct a conscious perception of the pain. Various kinds of painful stimuli,
such as tissue damage, noxious chemicals, or extreme temperatures, are detected by different types of nerves.
Each nerve type can be identified by its characteristic chemical profile. Recently, we found that some of these
nerves probably do not transmit their messages to the spinal cord in the way everyone had thought. This means
that there must be an alternative way for many types of painful stimuli to be transmitted into the spinal cord. In
this project, we will use a sophisticated suite of modern microscopic and electrical recording techniques to find
out what this alternative mechanism is. Our central idea is that most types of painful stimuli simultaneously
activate two types of sensory nerves. These nerves then connect with specific nerve cells in the spinal cord
before painful information is relayed to the brain. Our proposal suggests a new mechanism for understanding
how pain can develop from being an acute defensive reaction to a chronic problem. In turn, this should lead to
improved strategies for developing and testing new analgesic drugs.
Research achievements (from final report):
During this project we identified and mapped a significant population of sensory nerves that previously have
been overlooked by other investigators. These nerves probably are responsible for a subset of painful
sensations coming from the skin and other areas of the body. One charactersitic of these nerves is that they use
a different combination of chemical neurotransmitters compared with other types of nerves that transmit
painful stimuli.
Expected future outcomes:
Better understanding of mechanisms leading to chronic pain syndromes or intermittant pain that cannot be
treated by conventional analgesics.
Name of contact:
Ian Gibbins
Email/Phone no. of contact:
ian.gibbins@flinders.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 426758
Start Year: 2007
CIA Name: Prof Maria Crotty
End Year: 2009
Admin Inst: Flinders University
Grant Type: NHMRC Project Grants
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $572,543
Title of research award:
Individual Nutrition Therapy and Exercise Regime: A Controlled Trial of Injured, Vulnerable Elderly
(INTERACTIVE trial).Individual Nutrition Therapy and Exercise Regime: A Controlled Trial of Injured,
Vulnerable Elderly (INTERACTIVE trial).
Lay Description (from application):
Hip fractures are a common and growing problem for older Australians. Unfortunately recovery is incomplete
in most people. In this study two factors believed to be important for recovery will be investigated - exercise
and nutrition. After a hip fracture the ability to walk is severely compromised, as are appetite and dietary
intake. These factors are likely to contribute to the loss of muscle mass and strength frequently observed
amongst this patient group. There is considerable evidence to suggest that this loss has serious consequences in
terms of ability to return to pre-injury levels of function, restriction in independence and ultimately transfer
into a hostel or nursing home. Given these facts it makes sense that an exercise program incorporating strength
and functional activities, and a nutrition program aimed at achieving nutritional requirements, will improve
ability to walk, but there is no conclusive evidence that this is so. Only a small number of studies have tested
whether an exercise program improves recovery after a hip fracture and these have mostly commenced weeks
or months after the injury when it is likely that there has been irreversible decline in muscle mass and strength.
In contrast, most of the nutrition studies commence soon after the injury but provide protein and calories
insufficient to meet requirements, provide supplements that patients find difficult to drink or provide the
supplements for only a short duration. This study will use the best quality research methods to test whether
providing a 6-month individualised exercise and nutrition program to hip fracture patients soon after injury
improves walking and other important health outcomes. Patients will be followed for 12 months to determine
what difference the exercise and nutrition programs make. If they help then health services will have the
evidence they need to recommend this type of program to the growing number of older Australians that suffer a
hip fracture.
Research achievements (from final report):
The INTERACTIVE trial recruited 175 patients following hip fracture for 12 months. Each received either a
combined nutriton and exercise program or the equivalent attention via social visits. 12 month data was
collected for the last participant late 2010 and since this time considerable effort has been devoted to ensuring
the integrity of the data for analysis by an experienced Biostatistician. There have been some manuscripts
published in peer-review scientific journals since the trial commenced and currently there are four manuscripts
in draft form. It is anticipated that each of these will be submitted by the end of 2011. The trial has seen the
completion of one research higher degree student and two others are currently analysing data for the purpose of
their thesis, including a comprehenisive cost effectiveness evaluation of the trial. This is the first cost
effectiveness evaluation of a nutrition and exercise trial following hip fracture and it is expected that the
findings will have significant policy implications. The investigators have identified an additional 6 potential
manuscripts which will be prioritised for drafting in early 2012.
Expected future outcomes:
The results of the trial are expected to inform current practice for hip fracture rehabilitation, particularly in
relation to the effectiveness of exercise programs and the costs associated with delivering a home based service
to vulnerable older adults.
Name of contact:
Professor Maria Crotty
Email/Phone no. of contact:
NHMRC Research Achievements - SUMMARY
maria.crotty@flinders.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 535080
CIA Name: Prof Ian Gibbins
Admin Inst: Flinders University
Main RFCD: Sensory Systems
Total funding: $397,225
Start Year: 2009
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
Sensory neuronal pathways from the lower genital tract of femalesSensory neuronal pathways from the lower
genital tract of females
Lay Description (from application):
Many women experience severe debilitating pain upon normally innocuous contact with their genitalia. The
causes of this pain are unknown. Therefore, this project will use a suite of sophisticated microscopic and
electrical recording techniques to identify the neural pathways that transmit sensation, including pain, from the
female lower genital tract. Our new data will help create a rational basis for understanding and treating the
physical basis of genital pain in women.
Research achievements (from final report):
We discovered an extraordinarily complex and dense innervation of the clitoris by large diameter endings that
must include low threshold mechanoceptors responding to gentle touch. Such endings are prominent in dermal
papilla of the clitoris but are rare elsewhere in vulval and perineal skin and are absent from hairy body skin.
Each large diameter ending is accompanied by at least one finer varicose sensory fibre containing calcitonin
gene-related peptide (CGRP), but not substance P (SP) that arise from dorsal root ganglion neurons with midsized cell bodies typical of Adelta fibres. Neurons with this phenotype project both to the superficial dorsal
horn and a well defined region in the deep dorsal horn. These CGRP-containing neurons are most likely high
threshold mechanoceptors, and are the best candidates for mediating chronic genital pain. , We first used
electrophysiological methods to define a novel ascending intraspinal pathway from pudendal nerve sensory
inputs to lumbar sympathetic outflows. We then used c-Fos labelling to identify neurons in the sacral spinal
cord activated by afferents from the lower genital tract. We found neurons in superficial and deep dorsal horn
that are activated by different degrees of mechanical stimulation of the clitoris and labia. Many c-Fos labelled
cells are associated with CGRP-containing sensory endings in the dorsal horn. Spinal sections have provided
evidence in support of our electrophysiological data that local inhibitory spinal circuits tonically suppress
reflex activation of spinal autonomic outputs.
Expected future outcomes:
We anticpate continuing to characterise the functional properties of sensory nerves innervating the female
genital tract including changs in their behaviour that may lead to pathological genital pain conditions.
Name of contact:
Ian Gibbins
Email/Phone no. of contact:
ian.gibbins@flinders.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 595931
Start Year: 2010
CIA Name: A/Pr Michelle Miller
End Year: 2013
Admin Inst: Flinders University
Grant Type: NHMRC Project Grants
Main RFCD: Nutrition and Dietetics not elsewhere classified
Total funding: $480,246
Title of research award:
A TriaL Assessing N-3 as Treatment for Injury-induced Cachexia (ATLANTIC trial)A TriaL Assessing N-3
as Treatment for Injury-induced Cachexia (ATLANTIC trial)
Lay Description (from application):
The anti-inflammatory properties of fish oil are well documented. Hip fracture is common and patients suffer
significant inflammation, unintentional weight and muscle loss leading to poor outcomes. This study aims to
reduce the weight loss suffered by hip fracture patients by prescribing an intervention of individualised
nutrition support and high dose fish oil.
Research achievements (from final report):
This trial has completed enrolment of 150 older adults following hip fracture and administered a 12 week
intervention where participants have received 20ml of a moderate dose of omega 3 fatty acids or 20 ml of a
very low dose of omega 3 fatty acids. The trial has provided these 150 participants with 12 weeks of intensive
monitoring by an Accredited Practising Dietitian and an additional 9 months of follow-up, a service which is
completely absent from current services. We hope to be able to demonstrate that the moderate dose omega 3
intervention has reduced the inflammatory burden post-surgery sufficient to allow for an acceptable response to
nutrition support, that is, prevention of further weight loss, in particular muscle mass. The data are currently
being analysed and the findings should be available soon. The trial has also allowed for training of future
researchers with two PhD students contributing to the trial and many student Dietitians having the opportunity
to observe.
Expected future outcomes:
We expect to publish at least 4 additional manuscripts using data from this trial and to present the key findings
at local, national and international conferences.
Name of contact:
A/Professor Michelle Miller
Email/Phone no. of contact:
michelle.miller@flinders.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 325601
Start Year: 2005
CIA Name: Prof Tuan Nguyen
End Year: 2007
Admin Inst: Garvan Institute of Medical Research Grant Type: NHMRC Project Grants
Main RFCD: Endocrinology
Total funding: $363,000
Title of research award:
GENETIC PREDICTION OF FRACTURE IN A RISK-STRATIFIED POPULATIONGENETIC
PREDICTION OF FRACTURE IN A RISK-STRATIFIED POPULATION
Lay Description (from application):
Osteoporosis is a condition characterised by excessive bone loss and impaired bone quality, which ultimately
results in fracture with minimal trauma. Osteoporosis affects 27% of women and 11% of men aged 60 years or
above in the community, and costs Australia around $7 billion each year. Individuals with low bone mineral
density (BMD) have a significantly higher risk of fracture than those with normal BMD. In the long-term (14year) Dubbo Osteoporosis Epidemiology Study, more than half of individuals with osteoporosis (e.g., low
BMD) did not sustain a fracture, while approximately 60% of fracture cases had BMD above the high risk
levels. Thus, BMD alone is not a good discriminant of fracture versus non-fracture cases. It is widely known
that the liability to fracture is determined in part by genes. Previous studies, including from our group, have
suggested a number of candidate genes that are associated with fracture risk. The fundamental issue that this
study is concerned is that how and whether genetic markers could be used to facilitate case finding. It is
proposed that common variations of certain genes are associated with fracture risk independent of BMD. That
is, they can identify individuals at relatively high and low fracture risk after stratification for BMD. Hence,
some markers may identify those individuals likely (and unlikely) to fracture even with low (osteoporotic)
BMD. Similarly, some, possibly the same, markers may identify individuals at high risk of fracture despite
relatively "good" (ie non-osteoporotic) BMD. It is further proposed that no single gene will achieve this
outcome, but rather a small set of such gene polymorphisms will provide clinically useful risk information.
This effect is entirely analogous to the use of clinical risk indicators (eg, age, weight, sex, family history, etc)
to assess the risk of future fracture.
Research achievements (from final report):
1. We have genotyped 85 SNP, including the vitamin D receptor (VDR), collagen I alpha-1 (COLIA1),
estrogen receptor, beta-3 adrenergic receptor, and LRP-5 genes, for 2178 men and women in the Dubbo
Osteoporosis Epidemiology Study., 2. We have completed a genome-wide association study as part of a multicentre collaborative study designed to search for osteoporosis genes. From this study, we have identified a
number of loci that were associated with fracture risk of bone mineral density. , 3. We have published 8 papers,
including 4 original contributions, in international peer-reviewed journals such as New England Journal of
Medicine, Nature Genetics, Journal of Clinical Endocrinology and Metabolism. We have published an
important finding on the association between polymorphisms of the VDR and COLIA1 genes and hip fracture,
in which carriers of the VDR CC genotype (16% prevalence) and COLIA1 TT genotype (5% prevalence) had
an increased risk of hip fracture. Approximately 20% and 12% of the liability to hip fracture was attributable to
the presence of the CC genotype and TT genotype, respectively., 4. We have developed a prognostic model
that incorporates genotypes for predicting fracture risk in an individual. This prognostic model represents the
first attempt in the world to translate genetic information into practical clinical use. We are planning to make
this model available worldwide through the internat implementation of the model.
Expected future outcomes:
Development of prognostic model incorporating genetic data for predicting fracture risk
Name of contact:
Tuan V. Nguyen
Email/Phone no. of contact:
t.nguyen@garvan.org.au
NHMRC Research Achievements - SUMMARY
Grant ID: 376028
Start Year: 2006
CIA Name: Dr Paul Baldock
End Year: 2008
Admin Inst: Garvan Institute of Medical Research Grant Type: NHMRC Project Grants
Main RFCD: Endocrinology
Total funding: $472,771
Title of research award:
Hypothalamic signalling in cortical and trabecular bone anabolic activityHypothalamic signalling in cortical
and trabecular bone anabolic activity
Lay Description (from application):
Osteoporosis is a disease associated with an exponential rise in the number of fractures in the elderly. These
fractures are so common that around 1 in 3 women and 1in four men will be affected. They cause pain,
disability that can be permanent disability and are associated with premature death. Current treatments are able
to effectively increase bone strength in osteoporotic patients but can not return bone strength to normal. Some
new treatments can restore bone strength to some extent but these are limited by expense and safety concerns.
We have discovered a pathway in the brain that reduces bone formation and by blocking this pathway we can
achieve doubling of the amount of bone in key bone sites. This occurs due to a marked increase in the amount
of new bone formed. In fact, genetic manipulation of this pathway was able to double the speed at which bone
is made by the skeleton. Excitingly, these increases in bone were possible in adult mice, suggesting such
changes could be potential therapy for human patients. However, in order to be able to harness this pathway we
must understand what molecules within the brain are responsible for the signals that reach the bone. Our
proposal aims to identify the nerve signalling molecule(s) and the receptor for these signals within the brain
that initiates the increase in bone formation. This project ultimately aims to identify a target for new therapies
that could cause this beneficial effect by administration of a simple treatment, preferably by mouth in adult
humans.
Research achievements (from final report):
N/A
Expected future outcomes:
N/A
Name of contact:
Dr Paul Baldock
Email/Phone no. of contact:
p.baldock@garvan.org.au
NHMRC Research Achievements - SUMMARY
Grant ID: 427632
Start Year: 2007
CIA Name: Dr Paul Baldock
End Year: 2009
Admin Inst: Garvan Institute of Medical Research Grant Type: NHMRC Project Grants
Main RFCD: Endocrinology
Total funding: $662,065
Title of research award:
Neuropeptide control of bone cell functionNeuropeptide control of bone cell function
Lay Description (from application):
Osteoporosis is a disease associated with a progressive rise in the number of fractures in the elderly. These
fractures are so common that around 1 in 3 women and 1in 4 men will be affected. They cause pain, disability
that can be permanent and are associated with loss of independence even premature death. Current treatments
are able to partially restore bone strength in osteoporotic patients but can not return bone strength to normal.
Some new treatments can restore bone strength to some extent but these are limited by expense and safety
concerns. We have discovered a pathway in the brain that when blocked, results in a doubling of the amount of
bone in key bone sites and dramatic increases in bone strength. This occurs due to a marked increase in the
amount of new bone formed. In fact, genetic manipulation of this pathway was able to double the speed at
which bone is made by the skeleton. Excitingly, these increases in bone were possible in adult mice,
suggesting such changes could be potential therapy for human patients. We went on to test the effectiveness of
this pathway in animal models of human skeletal weakness and have shown that it is capable of remarkable
benefits. However, in order to be able to harness this pathway we must understand what molecules within the
bone that are responding to the signals from the brain. Our proposal aims to identify the nerve signalling
molecule(s) and pathways for these signals within the bone that initiate the increase in bone formation. This
project ultimately aims to identify a target for new therapies that could achieve this beneficial effect by
administration in osteoporotic women and men
Research achievements (from final report):
This project was the first to link a centrally mediated pathway to bone. We had previously identified
hypothalamic actions of the neuropeptide pathway involving Neuropeptide Y (NPY) and its powerful control
of bone metabolism. The peripheral mechanism was unknown. This project defined the action at the osteoblast
and further reported it to be a peripheral action of NPY, which was notable for it was mainly considered a brain
active molecule. , Moreover, this work lays open the possibility of direct modulation of osteoblast activity by
modulation of the local NPY Y1 receptor. This is currently the focus of a NHMRC project grant [ID_535932].
Models developed in the grant have enabled detailed expression profiling of Y1 action in osteoblasts and the
potential for cross regulation bet ween bone and fat cells., This project also enabled assessment of the time
course off NPY action during osteoblast differentiation. It highlighted a far more complex and involved
interaction between neural signalling and the cells of bone than previously thought. , This information will be
critical in considering NPY as a potential treatment for altered bone mass.
Expected future outcomes:
Curentl work is fi=ocussed upon preclinical models to assess the potential for Y1 receptor modualtion for
control of beon metabolism
Name of contact:
Dr Paul Baldock
Email/Phone no. of contact:
p.baldock@garvan.org.au
NHMRC Research Achievements - SUMMARY
Grant ID: 481313
Start Year: 2008
CIA Name: Prof Tuan Nguyen
End Year: 2013
Admin Inst: Garvan Institute of Medical Research Grant Type: NHMRC Research Fellowships
Main RFCD: Epidemiology
Total funding: $738,163
Title of research award:
Uncoupled Research FellowshipUncoupled Research Fellowship
Lay Description (from application):
My research activities can be broadly classified into three strands: epidemiology of fracture, genetics of
osteoporosis, and application of Bayesian approach in medical research. The major epidemiological work has
included the development of models for in
Research achievements (from final report):
My research seeks to discover risk factors and genes that are associated with fracture, and to translate these
findings into personalised assessment, diagnosis and treatment of osteoporosis. With the NHMRC Research
Fellowship support, I have been able to conduct important research projetcs within the Dubbo Osteoporosis
Epidemiology Study in which I am a Principal Investigator. My research group and I have developed and
implemented a fracture risk assessment model called "Garvan Fracture Risk Calculator", which has been used
by doctors and patients worldwide. We have further defined the seminal relationship between fracture and
mortality which has fundamentally changed the way doctors think about osteoporosis. We have continued
working on the genetics of osteoporosis, and by working with international colleagues, we have discovered
genes that are associated with fracture and bone mineral density.
Expected future outcomes:
The above work and discoveries lead us to develop a new model for individualised assessment of fracture risk.
This work will move us a step closer to the idea of personalised medicine.
Name of contact:
Tuan V. Nguyen
Email/Phone no. of contact:
t.nguyen@garvan.org.au
NHMRC Research Achievements - SUMMARY
Grant ID: 535932
Start Year: 2009
CIA Name: Dr Paul Baldock
End Year: 2011
Admin Inst: Garvan Institute of Medical Research Grant Type: NHMRC Project Grants
Main RFCD: Orthopaedics
Total funding: $469,740
Title of research award:
Manipulation of neural pathways for bone healingManipulation of neural pathways for bone healing
Lay Description (from application):
Orthopaedic medicine utilises precise control of critical aspects of the bone healing response. This proposal
looks at a novel, and powerful neural-based method for controlling these processes. This will be done by
modulating the activity of the neuropeptide Y1 receptor, recently identified on osteoblastic cells and capable of
powerful, inverse regulation of bone formation activity. Harnessing these effects will provide a critical tool for
existing surgical practice.
Research achievements (from final report):
Fracture healing is a complex process involving coordination of numerous cell types and signalling pathways.
In order to aid our interpretation of NPY's effects on this process, we have first endeavoured to characterise the
baseline phenotypes of the models involved., Aim1: The effects of NPY and osteoblastic Y1 receptor deletion
have been analysed as a prerequisite to understanding the fracture studies. We have also examined Y1 effects
in fat cells, as an important potential side effect of Y1 receptor modulation., Fracture studies have been carried
out for germline Y1 KO mice, which show a marked delay in fracture healing compared to wild type mice.
This exciting data provides critical data regarding Y1 modulation as a potential therapy, and gives clues to the
complex nature of neuropeptide signalling in bone. The repeat experiment using osteoblast specific Y1 KO
mice displayed no difference in healing evident from wild type, indicating a non-osteoblastic origin of the
reduced callus in Y1R KO., Aim2: Importantly, we have modelled chronic oral treatment of an NPYmodulating compound in mice for the first time. BIBO 0334, a Y1 receptor antagonist has been fed to mice for
2 months, and has produced a skeletal phenocopy of the germline Y1 KO. However, fracture healing in BIBO
treated mice was not altered, indicating this is a safe bone anabolic treatement for high fracture risk
populations, such as osteoporotic individuals., This is the first neuropapetide-based therapy shown to be
affective in chronic treatment and in fracture.
Expected future outcomes:
This project has provided novel insights into the regulatory influence of the NPY system in bone and the
possible therapeutic role of NPY via control of Y1 signalling. Moreover, it has determined which aspects of
bone healing are most amenable to NPY-based therapy, and thus defined which specific areas of clinical need
in bone repair that might be genuine targets for further development.
Name of contact:
Paul Baldock
Email/Phone no. of contact:
p.baldock@garvan.org.au
NHMRC Research Achievements - SUMMARY
Grant ID: 231421
CIA Name: A/Pr Nigel Morrison
Admin Inst: Griffith University
Main RFCD: Rheumatology and Arthritis
Total funding: $330,375
Start Year: 2003
End Year: 2005
Grant Type: NHMRC Project Grants
Title of research award:
Gene variants related to bone density and fracture.Gene variants related to bone density and fracture.
Lay Description (from application):
Bone density and osteoporosis have a genetic component. Identifying genes that are involved in determining
bone density may permit advances in controlling osteoporosis. We have identified a variant that is related to
bone density high enough to protect individuals four fold against Colle's fracture, the common wrist fracture
seen in women. In addition, some people with bone fracture at the hip, or low bone density, have mutations in
this gene. The gene is a master regulator of the cells that make bone: this gives hope that it may be possible to
alter bone formation through this master regulator.
Research achievements (from final report):
The RUNX2 gene is expressed in both bone and cartilage and is therefore a candidate gene for both
osteoporosis (OP) and osteoarthritis (OA). Not only is RUNX2 important for OP and OA, this gene impacts on
periodontal disease, rheumatoid arthritis, osteomyelitis, loosening of prosthetic devices, and bone loss from
malignant cancer. At least 20% of the population will suffer from one of these conditions in a life time. Runx2
gene variants have considerable effect on fracture and bone density (BMD). In an average sized school (say
1000 children), 5 will be carriers of Q-mutants. In a community of 100,000 people, 377 will be carriers of the
RUNX2 Q deletions that confer -0.6SD lower BMD and 133 others will have the 30Q allele that confers -1.1
SD BMD. For every 1SD decline in BMD, fracture increases two fold. Based on Australia's population,
102,000 people are carriers of Q mutations and will start life with an increased fracture risk. OP and OA are
major causes of morbidity and reduced productivity due to the demographic trend of increased aged persons as
a proportion of the total population. Osteoporosis Australia estimates that the cost of OP-related fractures and
hospitalisation will be $1 billion by 2010. Access Economics claims that the cost of OA to Australia in 2004
was $19.4 billion dollars. This project has contributed to understanding the genetic influences of RUNX2 on
bone and future work will cover influences on OA.
Expected future outcomes:
Three journal publications are in the process of final editing for submission to top journals such as JBMR.
These papers cover the resubmitted paper on Q-repeat in RUNX2, the influence of 11-Ala polymorphims on
fracture risk and targets of RUNX2 in osteoblasts.
Name of contact:
Nigel Morrison
Email/Phone no. of contact:
N.Morrison@griffith.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 277002
Start Year: 2004
CIA Name: Prof David Shum
End Year: 2006
Admin Inst: Griffith University
Grant Type: NHMRC Project Grants
Main RFCD: Learning, Memory, Cognition and Language
Total funding: $213,950
Title of research award:
Evaluation of rehabilitation strategies for prospective memory in individuals with traumatic brain
injuryEvaluation of rehabilitation strategies for prospective memory in individuals with traumatic brain injury
Lay Description (from application):
Traumatic brain injury (TBI) resulting from motor vehicle accidents and other mishaps is a leading cause of
death and disability in young adults. Memory problems is one of the most common and debilitating symptoms
reported by people with TBI. Traditionally, the treatment of memory problems has focussed on retrospective
memory or the ability to recall or recognise previously learned information (e.g., remembering the name of a
person, recalling the content of yesterday's news stories). Little research has been conducted on problems with
another type of memory called prospective memory or the ability to remember to do something in the future
(e.g., remembering to attend an appointment, remembering to pay a bill before its due date). The treatment of
prospective memory problems in people with TBI is, however, very important for assisting them to return to
work and successful integration into the community. This is because the ability to remember to do things at the
right time is essential for work and for independent living. In addition, failure to treat this type of problems can
be risky or even life threatening (e.g., forgetting to take medication, forgetting to turn off an electrical
appliance). This project aims to evaluate the independent and combined effectiveness of two rehabilitation
strategies, namely, promoting awareness of memory problems and adopting compensatory strategies. In
addition, this project aims to gauge whether a better management of prospective memory problem will lead to
better functioning in the community.
Research achievements (from final report):
Traumatic brain injury (TBI) resulting from motor vehicle and other causes is a leading cause of death and
disability in young adults. Memory impairment is one of the most common and debilitating problems reported
by people with TBI. Traditionally, the rehabilitation of memory impairment has focused on retrospective
memory or the ability to recall or recognise previously learned information. There has been little research on a
new type of memory called prospective memory or the ability to remember to do things in the future (e.g.,
remembering to attend an appointment or take medication). This type of memory is important for successful
independent living in the community and its failure can be risky or life threatening. This project aimed to
evaluate the relative effectiveness of self-awareness training (training versus no training) and type of memory
training (compensatory versus remedial), alone and in combination, in improving prospective memory in
individuals with TBI. Four groups of participants with TBI took part in an 8-week rehabilitation programme
and it was found that participants in the compensatory condition showed better improvement in prospective
memory than participants in the remedial condition. The effect self-awareness training on prospective memory
was not as strong. Interestingly, compensatory memory training was also found to lead to improvements in
psychosocial adjustment. Compared to other studies, this study used a more powerful research design and
included more participants. The results obtained, therefore, are more reliable and generalisable.
Expected future outcomes:
By publishing the results of this study, it is envisaged that the memory rehabilitation programme developed in
this study will attract the attention of practitioners and researchers. Adoption of the programme in Australia
and overseas can help individuals with TBI to better manage and compensate for their prospective memory
problems.
Name of contact:
Professor David Shum
Email/Phone no. of contact:
NHMRC Research Achievements - SUMMARY
D.Shum@griffith.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 511187
CIA Name: Prof Mark Forwood
Admin Inst: Griffith University
Main RFCD: Orthopaedics
Total funding: $493,817
Start Year: 2008
End Year: 2012
Grant Type: NHMRC Project Grants
Title of research award:
Cell biology of stress fractures: activation of remodelling at sites of non-unionCell biology of stress fractures:
activation of remodelling at sites of non-union
Lay Description (from application):
Stress fractures are debilitating injuries. We characterised a model of stress fractures in rat ulnae, learning that
they heal by activated remodelling, that key genes are expressed in a temporal pattern, and that part of the
fracture remains un-healed, similar to many clinical cases. Now, we will examine cell localisation of important
genes necessary for remodelling, and test the efficacy of different growth factors to activate a healing response
in the non-healed section of the fracture.
Research achievements (from final report):
We demonstrated that chemical signals produced by bone cells, at the site of a stress fracture, are crucial for
regulating bone remodeling that heals stress fractures. In particular, specific molecules, called chemokines, are
produced by cells around the stress fracture and guide the bone cells to the site of stress fracture healing. We
also showed that drugs used to reduce pain (such as ibuprofen), or treat osteoporosis (such as bisphosphonates),
slow down the healing of stress fractures. Our discoveries are important because they guide physicians in the
use of drugs in people who may be experiencing a stress fracture, and also suggest potential therapies to
accelerate healing. Our results were used by a task force of the American Society of Bone and Mineral
Research to highlight the potential aetiology of atypical femoral fractures appearing in patients who have been
treated with bisphosphonates for long periods.
Expected future outcomes:
The observations regarding chemokine regulation of bone remodeling in stress fracture repair, suggest that
parathyroid hormone may be a beneficial treatment to accelerate healing when stress fractures fail to repair, or
in patients experiencing atypical femoral stress fractures while being treated with bisphosphonates
Name of contact:
Prof Mark Forwood
Email/Phone no. of contact:
m.forwood@griffith.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 990761
Start Year: 1999
CIA Name: A/Pr Andrew Gundlach
End Year: 2003
Admin Inst: Howard Florey Institute
Grant Type: NHMRC Project Grants
Main RFCD: Neurology and Neuromuscular Diseases
Total funding: $802,291
Title of research award:
Dynamics of neuropeptide systems in brain: Focus on novel galanin pathways and receptorsDynamics of
neuropeptide systems in brain: Focus on novel galanin pathways and receptors
Lay Description (from application):
Not Available
Research achievements (from final report):
This project aimed to characterize the distribution, regulation and function of the important galanin peptidereceptor systems in the central nervous system of the rat and mouse. Initial aims were to map the distribution of
galanin receptor subtypes in adult and developing brain; to characterise a newly identified galanin nerve
pathway in the inferior olive and cerebellar in the mouse; and to examine the effect of a range of experimental
treatments on galanin and galanin receptor expression in different classes of brain neurons, including effects of
motor nerve damage, cerebral ischemia and 'spreading depression' in the cortex, and homeostatic changes such
as water deprivation or salt-loading. Most of these aims were achieved and yielded important information about
the functional role of galanin signalling in the brain., Thus, specific studies revealed: (i) the differential
abundance and distribution of two main subtypes of galanin receptor (GalR1 and GalR2) mRNA in postnatal
developing and adult rat brain; (ii) the induction of GalR1 receptors in granule cells during the development of
the mouse cerebellum; (iii) activity-dependent increases in galanin in inferior olive neurons associated with
drug-induced tremor; (iv) the distribution and regulation of GalR1 receptors in vasopressin neurons in the
hypothalamus; (v) the previously unknown distribution of galanin-like peptide (GALP) in neurons in the
arcuate nucleus of hypothalamus and in specialized glial cells (pituicytes) in the pituitary gland, along with
GALP upregulation in these latter cells by osmotic stress; (vi) a delayed, transient expression of galanin in cells
in cerebral cortex identified as oligodendrocyte precursors, following activation by acute waves of spreading
electrical/metabolic depression; and (vii) the presence of galanin and GalR1 and GalR2 in cells within the
'proliferative zones' of the adult brain, where new neurons, glia and oligodendrocytes are produced from neural
stem cells.
Expected future outcomes:
These findings provide a solid framework for continuing studies of central galanin systems, including
elucidation of the role of galanin systems in brain injury, particularly in oligodendrocyte precursors, in
developing brain and in adult neural stem cells. Findings also suggest new avenues of further investigation of
GALP biology and its role in integrating metabolism and reproductive function.
Name of contact:
Andrew Gundlach
Email/Phone no. of contact:
a.gundlach@hfi.unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 219325
Start Year: 2002
CIA Name: Prof Roderick McClure
End Year: 2006
Admin Inst: Injury Prevention and Control (Australia) Ltd Grant Type: NHMRC Partnerships
Main RFCD: Public Health and Health Services not elsewhere classified
Total funding: $1,335,418
Title of research award:
A research based solution to the public health problem of injuryA research based solution to the public health
problem of injury
Lay Description (from application):
Not Available
Research achievements (from final report):
The overall aims of the IPCA Research Partnership in Injury focused on the science that underpinned the
implementation of community based programs for the prevention of injury in each of the life stage categories
and in Indigenous communities. In each of these contexts, the contribution to knowledge made by the
Partnership has advanced the evidence base for the design, implementation and evaluation of these programs.
Links between the government, industry, researchers and the community, formalised in the IPCA model, has
proved to have been essential to the success of this research. The research activity has made important
advances that explain not only 'what works' in injury prevention, but 'how to make it work' in population level
programs. , The current Queensland Governement injury prevention policy focused on Childhood injury, Falls
in older people and Indigenous Injury is a direct result of the foundational research undertaken within three of
the programs of the Injury Partnership. A recent review commissioned by the Minister of Mines & Energy
(QLD), made 39 recommendations on improvements to the reporting of injury and health issues in the mining
industry, many of which are based on evidence derived from IPCA research projects in the Mining Industry.
Expected future outcomes:
It is expected that over the next 5 years the research will be directly translated to reductions in the population
level indicators of injury-related health of children, young adults, adults in the workforce, older people, and
Indigenous Australians.
Name of contact:
Professor Rod Mcclure
Email/Phone no. of contact:
rod.mcclure@muarc.monash.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 278802
Start Year: 2004
CIA Name: Dr Yeesim Khew-Goodall
End Year: 2006
Admin Inst: Institute of Medical and Veterinary Science
Grant Type: NHMRC Project Grants
Main RFCD: Cellular Interactions (incl. Adhesion, Matrix, Cell Wall)
Total funding: $496,500
Title of research award:
A tyrosine phosphatase that regulates adherens junctions, cell migration and the epithelial-mesenchymal
transitionA tyrosine phosphatase that regulates adherens junctions, cell migration and the epithelialmesenchymal transition
Lay Description (from application):
Cell-cell adhesion which physically glues cells together to form tissues and organs, also controls processes in
development, wound healing and cancer progression. I have identified a novel regulator of cell-cell adhesion
that regulates cell migration and cell morphology. Since these events are crucial during metastasis (the spread
of cancer) and during wound healing, understanding the function of this novel regulator may provide the basis
for new approaches to developing therapeutics. Specifically, in this proposal I aim to further our understanding
of the function of this novel regulator in normal physiology and to elucidate how its functions are regulated.
Research achievements (from final report):
In this study, we (i) demonstrated that the protein tyrosine phosphatase Pez is a regulator of epithelialmesenchymal transition (EMT), (ii) that its role in regulating EMT is crucial for the proper development of
some organs using a zebrafish model to study organ development and (iii) that it is a regulator of the growth
factor TGF-beta production leading to the EMT. In addition to its role in organ development, EMT is also a
process required for the initial stages of metastasis of solid tumours as well as a source of additional fibroblasts
in fibrotic diseases that lead to organ failure. Although TGF-beta level is well-known to be elevated in both
cancers and fibrotic diseases and play a role in the progression of both these diseases, little is known about the
mechanisms that lead to elevated TGF-beta levels in these diseases. Our findings implicate Pez as a potential
protagonist of both cancer metastasis and organ fibrosis and hence a potential therapuetic target for novel drugs
to inhibit or retard these processes. The findings from this study and reagents generated as a result led to a
collaboration with a colleague in which we identified a family microRNAs that could regulate EMT with
implications for their use in preventing or retarding metastasis.
Expected future outcomes:
We expect that in future we will establish a role for Pez in metastasis and fibrotic diseases and head towards
determining whether it is a worthy therapeutic target for controlling cancer progression and/or fibrotic diseases.
We will also establish the mechanism by which Pez upregulates active TGF-beta and this would impact on our
undestanding of developmental processes, homeostasis and diseases.
Name of contact:
Yeesim Khew-Goodall
Email/Phone no. of contact:
yeesim.khew-goodall@imvs.sa.gov.au
NHMRC Research Achievements - SUMMARY
Grant ID: 234423
CIA Name: Dr Jill Cook
Admin Inst: La Trobe University
Main RFCD: Sports Medicine
Total funding: $97,125
Start Year: 2003
End Year: 2005
Grant Type: Early Career Fellowships (Australia)
Title of research award:
Is neovascularisation the source of pain in patellar tendinopathyIs neovascularisation the source of pain in
patellar tendinopathy
Lay Description (from application):
Not Available
Research achievements (from final report):
Tendon injury occurs across the lifespan, in active people in recreation and in the workplace. Tendon injury
causes pain when the tendon is loaded, decreasing physical activty and interfering with employment. Tendon
injury results in pathology that is resistant to repair. New blood vessels (neovascularisation) are a key
pathological change in tendon injury. , Early investigations suggested an association between vessels and
tendon pain. This program of research confirmed this association and revealed that it was the presence of
vessels not blood evident on imaging that determines the pain. This has been confirmed in research from other
groups that have shown nerves associated with vessels may be the source of pain. The research also showed
that measurement of vascularity with Doppler ultrasound was reliable, and that the pre-imaging activity may be
crucial in demonstrating maximal vascularity. Additionally, it was determined that abdominal obesity was the
greatest risk factor for tendon pathology and pain, but abdominal adiposity was not associated with vascularity.
, The benefits from this research include better understanding of the role of vascularity in tendon pain and how
it changes over time. There is also an understanding of the role of imaging in identifying tendon vascularity
and the factors that affect images of tendon vessels. Treatment to decrease vascularity can be directed
appropriately to affected tendons., This research also identified abdominal adiposity as a strong but potentially
modifiable factor associated with tendon pathology. In this age of increasing obesity, this finding may have
important implications for changing the prevalence of tendon injury.
Expected future outcomes:
Understanding the role of local factors in producing tendon pathology and pain as well as the identification of
systemic factors will allow treatments directed at modification of both. Better outcomes for those with tendon
pain will result in greater levels of activity and better overall health..
Name of contact:
Jill Cook
Email/Phone no. of contact:
j.cook@latrobe.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 234424
Start Year: 2004
CIA Name: A/Pr Hylton Menz
End Year: 2007
Admin Inst: La Trobe University
Grant Type: Early Career Fellowships (Australia)
Main RFCD: Medical and Health Sciences not elsewhere classified
Total funding: $214,093
Title of research award:
Studies on foot and footwear risk factors for instability and falls in older peopleStudies on foot and footwear
risk factors for instability and falls in older people
Lay Description (from application):
Not Available
Research achievements (from final report):
The aim of this program was to determine the influence of foot problems and footwear characteristics on
balance and falls in older people. The core investigation involved a 12 month prospective study in which foot
problems and footwear characteristics were assessed in 176 people aged 65 years and over, and the incidence
of falls was tracked using monthly calendars. The findings of this study indicated that (i) foot pain, decreased
ankle flexibility, hallux valgus and weak toe plantarflexors are significant independent risk factors for falls, and
(ii) risk of falling indoors is increased in older people who go barefoot or wear socks only. This study is
significant in that it has identified potentially modifiable risk factors for falling in older people.
Expected future outcomes:
The results of this research have been used to inform an intervention study to assess the efficacy of a
multifaceted podiatry treatment to improve balance and prevent falls in older people. If this intervention is
found to be effective, it has the potential to reduce the burden of falls-related injury in older people.
Name of contact:
Dr Hylton B. Menz
Email/Phone no. of contact:
h.menz@latrobe.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 433027
CIA Name: A/Pr Hylton Menz
Admin Inst: La Trobe University
Main RFCD: Geriatrics and Gerontology
Total funding: $730,975
Start Year: 2008
End Year: 2009
Grant Type: NHMRC Project Grants
Title of research award:
Randomised controlled trial of a tailored podiatry intervention to enhance mobility and prevent falls in older
peopleRandomised controlled trial of a tailored podiatry intervention to enhance mobility and prevent falls in
older people
Lay Description (from application):
Foot problems affect 1 in 3 people over the age of 65 years and are associated with reduced walking speed,
difficulty performing activities of daily living, impaired balance and increased risk of falls. Although a range of
health professionals provide treatment for foot disorders, the most common chronic foot problems in older
people (such as corns and calluses, nail disorders and toe deformities) are frequently managed by podiatrists
using treatments such as scalpel debridement of lesions, foot orthoses, exercise prescription and footwear
modifications. The 1995 National Health Survey reported that persons aged 80 years or over were most likely
to have reported visiting a podiatrist in the previous two weeks, followed by those aged 65-79 years. Similarly,
the Australian Department of Veterans Affairs, which provides podiatry services to veterans and their
dependants, documented 606,706 episodes of podiatry care to 103,540 veterans in 1998-1999, at a cost of
$23M. Podiatry therefore plays a substantial role in the maintenance of foot health and mobility in older
Australians. Despite the detrimental effects of foot problems and the widespread utilisation of podiatry
services by older people, very few studies have been undertaken to ascertain the efficacy of podiatry
treatments. Therefore, the aim of this study is to evaluate the efficacy of an individualised podiatry intervention
designed to reduce pain, enhance functional mobility and prevent falls in older people. Given the high
prevalence of foot-related disability and falls in older people and their associated health care costs, the study
findings will be of considerable public health importance. If found to be clinically effective, the intervention
could be easily implemented into a range of healthcare settings and adopted in both state and federal falls
prevention policies.
Research achievements (from final report):
The project investigated the effectiveness of a multifacated podiatry intervention to prevent falls in older
people. 305 people aged over 65 years with disabling foot pain and an increased risk of falling were allocated
to a usual care control group or an intervention group. The intervention group received foot orthoses, footwear
advice and footwear cost subsidy, and a home-based exercise program. All participants were then followed for
12 months to record the incidence of falls. At the end of the study, there were 36% fewer falls in the
intervention group, indicating that the multifacated podiatry intervention was effective in preventing falls in
older people.
Expected future outcomes:
We plan to roll out the intervention to practicing podiatrists in both public and private sector settings and in
multidisciplinary falls prevention clinics and evaluate its effectiveness under 'real world' conditions.
Name of contact:
Prof Hylton Menz
Email/Phone no. of contact:
h.menz@latrobe.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 509129
CIA Name: Prof Meg Morris
Admin Inst: La Trobe University
Main RFCD: Care for Disabled
Total funding: $805,599
Start Year: 2008
End Year: 2012
Grant Type: NHMRC Project Grants
Title of research award:
Home based rehabilitation to reduce falls and disability in Parkinson disease.Home based rehabilitation to
reduce falls and disability in Parkinson disease.
Lay Description (from application):
Falls occur in more than half of the 80,000 Australians living with Parkinson disease. This research will
examine the extent to which a program of home rehabilitation using exercises, movement strategies and falls
education is effective in reducing the number of falls, the injuries from falls and disability. We will also
examine the effects of home based rehabilitation on quality of life. We shall compare the outcomes of the
integrated rehabilitation home program with a life-skills program.
Research achievements (from final report):
This study has provided new data on the extent to which an integrated physiotherapy program of home based
rehabilitation exercises resulted in fewer falls compared with a control "life-skills" home program for people
living with idiopathic Parkinson's disease. We also examined whether a comprehensive home exercise program
reduced disability and improved quality of life to a greater extent than the control program. The home based
rehabilitation program included both progressive resistance strength training exercises and movement strategy
training. Strength training was achieved using weighted vests and other forms of resistance and the amount of
resistance was progressively increased as people with Parkinson's disease became stronger. The movement
strategy training included cueing (visual, auditory, proprioceptive), attentional strategies (such as thinking
about large movements and focussing attention on movements during their performance), segmentation of
complex movement sequences and structuring the environment to optimise motor performance. Participants
were also educated on how to prevent falls in home and community settings. The comprehensive rehabilitation
approach was feasible, safe and economically viable. Therapists were able to safely provide rehabilitation
within the home setting without the need for patients to attend an outpatient clinic or hospital. Patients were
also able to record their falls on a calendar at home and this was a feasible method of accurately recording falls
data. The study has shaped contemporary physiotherapy for Parkinson's disease world-wide by providing
guidelines for rehabilitation as well as confirming valid methods of collecting data on falls and disability in
people living with this debilitating disease.
Expected future outcomes:
This study provides new evidence on which types of home based physiotherapy exercises and movement
strategies are effective for enabling people with Parkinson's disease to prevent falls and reduce disability and
improve quality of life. It also shows that falls calendars are feasible for collecting falls data in neurological
patients.
Name of contact:
Professor Meg Morris+
Email/Phone no. of contact:
m.morris@latrobe.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 512159
CIA Name: Prof Mark Connor
Admin Inst: Macquarie University
Main RFCD: Peripheral Nervous System
Total funding: $397,399
Start Year: 2008
End Year: 2010
Grant Type: NHMRC Project Grants
Title of research award:
Effects of muscle inflammation on sensory neuron excitabilityEffects of muscle inflammation on sensory
neuron excitability
Lay Description (from application):
Muscle pain is a common and poorly treated health problem for many Australians. This project examines the
properties of nerves that sense muscle pain and looks at how these change during inflammation, a common
cause of muscle pain. We are looking specifically at jaw muscles, which are one of the most common sites of
chronic muscle pain. By understanding how muscle nerves are changed by injury, we hope to be able to
develop treatments to prevent or reverse these changes.
Research achievements (from final report):
In this study we have found that experimental inflammation of jaw muscle in mouse produces an increase of
the capacity of the nerves to the muscle to make serotonin, an important mediator of pain. We first established
that the inflammation produced changes in way the jaw muscle nerve cells sense tissue damage, and then rather
unexpectedly found that this was also associated with an increase in the amount of the enzymes that make
serotinin. For the first time we established that the nerve cells innervating the face expressed all of the enzymes
needed for making serotonin, and we showed that levels of these enzymes differ between male and femnale
rats, and also change in female rats across their estrus cycle. The finding that the nerves which sense pain may
also make a substance involved in modulating pain intensity will focus attention on whether the nerves
themselves are more than simply passive sensors of tissue damage, and whether they may contribute to the
chronic pain associated with jaw muscle inflammation. Our work higlights the possibility of using drugs which
limit serotonin production or which act to modify serotinin receptors as potential treatments for jaw muscle
pain.
Expected future outcomes:
Development of new pharmacotherapies aimed at modulating serotinin synthesis by trigeminal neurons, with a
view to relieving jaw muscle and perhaps other facial pain. This will require understanding of the role of
sesnory nerve-derived 5-HT.
Name of contact:
Mark Connor
Email/Phone no. of contact:
mark.connor@mq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 604008
CIA Name: Prof Marcus Stoodley
Admin Inst: Macquarie University
Main RFCD: Central Nervous System
Total funding: $607,203
Start Year: 2010
End Year: 2013
Grant Type: NHMRC Project Grants
Title of research award:
Understanding spinal cord cyst developmentUnderstanding spinal cord cyst development
Lay Description (from application):
Spinal cord cysts can develop after spinal injury or in association with tumours or congenital abnormalities of
the spine. These cysts often cause pain and paralysis. Treatment is often ineffective, partly because the source
of the cyst fluid is unknown. We are investigating the origin of this fluid using animal models of spinal cord
cysts, computer simulations, and MRI studies of patients with spinal cord cysts. Understanding the origin of
cyst fluid will help us to develop improved treatment.
Research achievements (from final report):
Syringomyelia is a condition where cysts form in the spinal cord, causing pain and loss of function. Little is
known about the origins of the cyst fluid, making treatment difficult. Our research focused on understanding
cyst development, using animal models in rats and sheep, and using computational models. We showed that the
timing of pulse waves in the fluid around the cord could be affected by certain conditions and lead to increased
fluid flow in to the spinal cord. We showed, for the first time, fluid outflow pathways from cysts. We showed
that the leakiness of blood vessels in the spinal cord was a likely contributing factor in post-traumatic cysts.
Our work also showed that fluid channels in the cells around cysts are altered in syringomyelia, pointing to a
potential new avenue for medial treatment.
Expected future outcomes:
This work has contributed to our understanding of fluid inflow and outflow in syringomyelia. The results
indicate that altering fluid channel number and function in the spinal cord is a potential new avenue for medical
treatment. We are currently working on further studies of spinal cord fluid flow, and the effects of blockage of
flow around the cord on cyst development.
Name of contact:
Prof Marcus Stoodley
Email/Phone no. of contact:
marcus.stoodley@mq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 331966
Start Year: 2006
CIA Name: Dr Penelope Jeffery
End Year: 2009
Admin Inst: Mater Medical Research Institute, Brisbane
Grant Type: Early Career Fellowships
(Australia)
Main RFCD: Oncology and Carcinogenesis
Total funding: $276,750
Title of research award:
Cell surface mucins modulate epithelial cell growth and apoptosis of normal mucosal wound repair and
epithelial cancersCell surface mucins modulate epithelial cell growth and apoptosis of normal mucosal wound
repair and epithelial cancers
Lay Description (from application):
Not Available
Research achievements (from final report):
This fellowship has enabled the recipient to undertake an intensive full-time training program in biomedical
research. The trainee has acquired skills in the manipulation and study of animal models of disease and
advanced techniques in immunology and molecular biology. The fellow has also developed skills in scientific
writing and the success of this is evident by the fact that the fellow received an NHMRC project grant (as the
chief investigator A) and several smaller grants during the course of her training fellowship. The fellow helped
to phenotype a unique mouse model that was created in her laboratory and that has shown to have an increased
susceptibility to inflammatory bowel disease (IBD). The fellow has also used other models of this disease to
test potential new agents for the treatment of IBD and has translated these findings by using immune cells
taken from IBD patients and examining the mechanisms underpinning the anti-inflammatory effects of novel
agents. These impacts are significant as novel treatments for IBD are urgently required and the work arising
from this fellowship has garnered interest from the pharmaceutical industry.
Expected future outcomes:
This work will continue as the fellow has secured future funding. The novel agents identified during the
fellowship as being anti-inflammatory in mouse models of IBD will be further studied with the goal of
employing them in clinical trials with IBD patients.
Name of contact:
Penny Jeffery
Email/Phone no. of contact:
pjeffery@mmri.mater.org.au
NHMRC Research Achievements - SUMMARY
Grant ID: 282400
Start Year: 2004
CIA Name: Prof Stephen Jane
End Year: 2006
Admin Inst: Melbourne Health
Grant Type: NHMRC Project Grants
Main RFCD: Genetic Development (incl. Sex Determination)
Total funding: $496,500
Title of research award:
The role of GRHL-3, a mammalian homologue of Drosophila grainyhead, in neural tube developmentThe role
of GRHL-3, a mammalian homologue of Drosophila grainyhead, in neural tube development
Lay Description (from application):
Spina bifida and anencephaly are two common human congenital malformations that form part of a wide
spectrum of mutations known collectively as neural tube defects (NTDs). Patients with the most severe form of
spina bifida have a failure of the vertebral column and skin to close over the spinal cord and therefore suffer
from limb paralysis and marked bladder and bowel dysfunction. Infants with anencephaly have an open cranial
vault and failure of normal brain development and die within the first few hours of life. These abnormalities
occur frequently (1/1000 live births) and are a direct result of failure of the neural tube to close during
embryogenesis. NTDs are influenced by both environmental and genetic factors. The best characterised
environmental factor is the dietary supplement folate, which when administered before conception results in a
reduction in the incidence of spina bifida. The genetic complexity is evidenced by the array of mouse genetic
mutations that give rise to NTDs. One of these mouse mutations, known as Curly tail (ct), has served as the
major animal model of human NTDs. This is because the ct mice are resistant to folate administration (like
most of the cases of spina bifida currently seen in patients) and because the mice seem to have normal
development in virtually all other organ systems. Ironically, the genetic mutation that causes the curly tail
phenotype has remained undiscovered for over 50 years. We have now identified the gene mutated in the curly
tail mice. This gene is highly conserved in humans suggesting that it will play a similar role in neural tube
development in man. The gene, known as GRHL-3, is a descendant of a fly gene critical for development of
the nervous system in that organism. The studies we propose here will examine the developmental pathways
involved in normal neural tube closure in mice and humans and will impact on our understanding of these
devastating congenital malformations.
Research achievements (from final report):
During the tenure of this grant, we demonstrated that the mammalian gene Grhl3 is essential for formation of
the barrier function of skin and that this protective pathway is conserved over 700 million years of evolution
from fly to man. This work was published in Science, and was the subject of an invited review in Current
Opinions in Genetics and Development. This discovery paves the way for novel interventions in the area of
infant prematurity and wound repair.
Expected future outcomes:
We will expand on this work to further examine the pathways that regulate skin protective function.
Name of contact:
Stephen M. Jane
Email/Phone no. of contact:
jane@wehi.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 403000
CIA Name: Dr Velandai Srikanth
Admin Inst: Menzies Research Institute
Main RFCD: Epidemiology
Total funding: $528,331
Start Year: 2006
End Year: 2008
Grant Type: NHMRC Project Grants
Title of research award:
A population-based study of cerebrovascular mechanisms underyling gait, balance and cognition in older
peopleA population-based study of cerebrovascular mechanisms underyling gait, balance and cognition in
older people
Lay Description (from application):
Mobility problems, falls and dementia are among the major problems affecting older Australians with
significant consequent disability. Treatment of such disorders carries an estimated annual cost of around 4
billion dollars. This study will examine the role of age-related brain changes in causing problems with walking,
balance and cognitive abilities in the general community. The clarification of the role of the ageing brain in
causing such disorders will guide efforts directed at preventing the occurrence of falls and dementia.
Research achievements (from final report):
The primary aim of this study is to examine in detail the effect of age-related brain changes termed as white
matter hyperintensities on key aspects of brain function, namely gait, balance and cognition in an older
population. A primary finding of this study has been that such changes, when present in large amounts, predict
a high risk of future falling in older people. These brain changes have also also associated with poorer gait in
older people. These initial findings suggest that we may need to find ways to treat or prevent the occurrence of
such lesions in order to prevent falling in older people.
Expected future outcomes:
Further publications are expected over the next year regarding the location-specific effects of such lesions on
gait and cognitive function.
Name of contact:
Dr. Velandai Srikanth
Email/Phone no. of contact:
velandai.srikanth@med.monash.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 403035
CIA Name: Dr Tania Winzenberg
Admin Inst: Menzies Research Institute
Main RFCD: Preventive Medicine
Total funding: $305,500
Start Year: 2006
End Year: 2009
Grant Type: Early Career Fellowships (Australia)
Title of research award:
Chronic disease prevention: investigating how to improve bone mass, fracture risk and obesity at different lifestages.Chronic disease prevention: investigating how to improve bone mass, fracture risk and obesity at
different life-stages.
Lay Description (from application):
Not Available
Research achievements (from final report):
With the award of this GP Training Fellowship, Dr Winzenberg has undertaken a range of projects
investigating chronic disease prevention in both adults and children, focussing work initially on prevention of
osteoporosis and other musculoskeletal conditions. With the recognition of the range of issues shared across
prevention other chronic diseases, this work expanded to also consider prevention of cardiovascular diseases.
Key outcomes of her work include: , *demonstrating that informing women of their fracture risk could lead to
them making lifestyle changes to improve not only their own bone health, but potentially that of their children
as well; , *providing definitive evidence that calcium supplements in healthy children have only minor effects
on bone mineral density and do not affect body weight, thus clarifying that calcium supplements have only a
limited place as a public health intervention;, *developing an easy-to-take dosage regimen to treat vitamin D
deficiency in adolescents; , *identifying the previously unrecognised issue of poor accessibility of the bone
mineral testing (an important test for osteoporosis diagnosis and management) in rural areas;, *defining general
practitioners' views of their role in assessing their patients' physical activity levels and determining how well
the methods GPs have to do this perform in practice. This showed that GPs perform targeted assessments of
their at-risk patents but that a commonly short questionnaire to assess physical activity performs less well than
GPs' usual assessment processes. The need for further research in how to best help GP's assess their patients'
physical activity was highlighted in these studies.
Expected future outcomes:
Dr Winzenberg is investigating further ways to improve children's bone health including determining if vitamin
D supplementation is effective in either healthy children or children who have sustained a broken bone. She is
also studying whether informing people of their risk of cardiovascular disease might cause them to improve
their lifestyle, as seen with fracture risk feedback.
Name of contact:
Tania Winzenberg
Email/Phone no. of contact:
tania.winzenberg@utas.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 490025
CIA Name: Prof Adrian West
Admin Inst: Menzies Research Institute
Main RFCD: Central Nervous System
Total funding: $478,068
Start Year: 2008
End Year: 2010
Grant Type: NHMRC Project Grants
Title of research award:
Interactions between injured neurons, astrocytes and metallothioneinInteractions between injured neurons,
astrocytes and metallothionein
Lay Description (from application):
We have found that the protein, metallothionein, which protects the brain after injury or during
neurodegenerative disease acts in a more complex way than previously thought, including a direct action on
injured neurons as well as on the originating cell, astrocytes. Elucidating each component of metallothionein
action will help us understand how cells interact in the brain after injury, and excitingly, offers an opportunity
to develop an enhanced therapeutic strategy based on this protein.
Research achievements (from final report):
This project investigated how different types of brain cells interact following injury, with a focus on how a
protein produced by brain cells, metallothionein, can protect neurons from death and promote regenerative
growth. We discovered that metallothionein is released by astrocytes following injury and it promoted
regenerative growth of neurons by interacting with a specific class of cellular receptor. This has clear
therapeutic potential since future treatments could exploit this pathway using either metallothionein or
synthetic analogues of metallothionein. We also discovered that metallothionein could cause glia cells
(astrocytes, microglia) to assume a pro-regenerative role following injury.
Expected future outcomes:
Based on this work, we are investigated a new class of synthetic agents based on metallothionein which
promote recovery from brain injury.
Name of contact:
Adrian West
Email/Phone no. of contact:
Adrian.West@utas.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 544913
CIA Name: Prof Roger Chung
Admin Inst: Menzies Research Institute
Main RFCD: Cellular Nervous System
Total funding: $408,739
Start Year: 2009
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
How does the LRP receptor megalin promote regenerative neuronal growth?How does the LRP receptor
megalin promote regenerative neuronal growth?
Lay Description (from application):
Promoting the regenerative growth of neurons to allow recovery from traumatic brain injury or Alzheimer's
disease is a major goal of neuroscientists. This project continues the Chief Investigators' work in which they
have discovered the regenerative potential of a protein and focuses on how this protein interacts with a key
neuronal receptor, megalin, which appears to drive the regenerative process. This work will identify new
targets for therapies for a range of nervous system disorders.
Research achievements (from final report):
The aim of this project was to determine the precise mechanisms through which the protein metallothionein can
promote the regeneration of injured nerves following traumatic brain injury. Through a systematic series of
experimental approaches, we determined the identity of the receptor and the precise biochemical pathway that
is activated by metallothionein to promote regenerative sprouting of injured neurons. In addition, we found that
metallothionein can also modify the behaviour of non-neuronal cells, to make them more permissive to
regeneration of injured neurons. Finally, using our experimental models we identified a new molecule that
appears to be a key driver of nerve regeneration, and we are currently evaluating this new neuroregenerative
pathway. These important discoveries will greatly benefit the scientific community towards developing
therapeutic strategies to treat traumatic brain injury.
Expected future outcomes:
These important outcomes may lead to the development of new therapeutic agents that promote the
regeneration of nerves following traumatic brain injury.
Name of contact:
Dr Roger Chung
Email/Phone no. of contact:
rschung@utas.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 544920
CIA Name: Prof David Small
Admin Inst: Menzies Research Institute
Main RFCD: Cell Neurochemistry
Total funding: $618,950
Start Year: 2009
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
How amyloid causes neurodegeneration: the role of transthyretin in familial amyloidotic polyneuropathyHow
amyloid causes neurodegeneration: the role of transthyretin in familial amyloidotic polyneuropathy
Lay Description (from application):
This project seeks to understand the biochemical basis of nerve degeneration in a disease known as familial
amyloidotic polyneuropathy. This disease is caused by a protein known as transthyretin, which is abnormally
deposited around nerves and causes nerve damage. The project is highly likely to provide clues which help us
understand some related dementia causing diseases like Alzheimer's disease and prion diseases such as scrapie
and mad cow disease.
Research achievements (from final report):
This research has helped us to understand the mechanisms that cause a rare disease known as familial
amyloidotic polyneuropathy. However, the real significance of this work is that the mechanisms which underlie
familial amyloidotic polyneuropathy may be the same as those that cause Alzheimer's disease. Understanding
these mechanisms is vital for the identification of new drug targets for the treatment of Alzheimer's disease and
related disorders.
Expected future outcomes:
This research has increased our understanding of the cause of a neurodegenerative disease. Ultimately,
therapies targetting this cause may be developed which can be used to effectively treat the disease.
Name of contact:
David Small
Email/Phone no. of contact:
d.h.small@menzies.utas.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 544925
Start Year: 2009
CIA Name: Prof James Vickers
End Year: 2011
Admin Inst: Menzies Research Institute
Grant Type: NHMRC Project Grants
Main RFCD: Neurology and Neuromuscular Diseases
Total funding: $400,885
Title of research award:
Determining the cellular mechanism underlying diffuse axonal injury following brain traumaDetermining the
cellular mechanism underlying diffuse axonal injury following brain trauma
Lay Description (from application):
Traumatic head injury causes transient stretch injury to the nerve cell processes within the brain. This leads to a
poorly understood series of cellular changes within nerve cells which may ultimately lead to their breakage and
subsequent neurological disability. This project seeks to understand how this nerve cell damage forms, and
explores new potential interventions which may protect the brain.
Research achievements (from final report):
Acute axonal stretch and shear in the central nervous system, leading to a pattern of secondary 'diffuse axonal
injury' (DAI), has been proposed to be a major cause of on-going disability following mild to severe forms of
brain injury. This project grant was based on a novel in vitro method for causing mild-moderate transient
axonal shear strain that leads, over 2-3 days, to secondary DAI-like axotomy. Our investigation determined that
transient axonal stretch injury in vitro induces an initial acute increase in intracellular calcium, principally
derived from intracellular stores, which was followed by a delayed increase in calcium over 48 hrs post-injury.
This progressive and persistent increase in intracellular calcium was also associated with increased frequency
of spontaneous calcium fluxes as well as cytoskeletal abnormalities. Pharmacological inhibition of calciumactivated enzymes, such as phosphatases, resulted in reduced secondary axotomy. These results demonstrate
that stretch injury of axons induced an initial substantial release of calcium from intracellular stores with
elevated intracellular calcium persisting over two days. These long-lasting calcium alterations may provide
new insight into the earliest neuronal abnormalities that follow traumatic brain injury as well as the key cellular
changes that lead to the development of diffuse axonal injury and secondary degeneration.
Expected future outcomes:
These results provide important new insights into the cascade of pathological brain changes that follow
traumatic brain injury. The research has also indicated potential new approaches to interfere in the sequene of
cellular changes that follow axon stretch injury, and we are continuing research on these areas.
Name of contact:
James Vickers
Email/Phone no. of contact:
James.Vickers@utas.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 490305
Start Year: 2008
CIA Name: A/Pr Geoffrey Isbister
End Year: 2010
Admin Inst: Menzies School of Health Research Grant Type: NHMRC Project Grants
Main RFCD: Toxicology (incl. Clinical Toxicology)
Total funding: $715,730
Title of research award:
A Randomised Controlled Trial of Factor Replacement Therapy in Snake Bite CoagulopathyA Randomised
Controlled Trial of Factor Replacement Therapy in Snake Bite Coagulopathy
Lay Description (from application):
This proposal seeks funding to undertake a controlled trial of clotting factor replacement in snake bite
coagulopathy after the administration of a neutralising dose of antivenom. The aim is to determine if factor
replacement will result in a rapid return of clotting function in patients and therefore reduce the potential risk of
major bleeding. This study will have international implications because globally snakebite coagulopathy is a
major cause of morbidity and death like in Australia.
Research achievements (from final report):
The study has changed the treatment of snake envenoming in Australia by reducing the amount of antivenom
required, the monitoring and observation of patients with snake bite and the indications for treatment. This has
led to a 3 to 4 fold reduction in antivenom use with the consequent decrease in risk of allergic reactions to
antivenom and huge cost savings in less antivenom having to be stored in hospitals around the country. The
existence of a large multicentre study of snakebite with a 24 hour research number has also (inadvertently)
improved the clinical care of patients because doctors all around the country have consulted about cases and
received the most up to date and current advice. A number of subgroup analyses have been published of
different types of snakes which has improved our understanding of the clinical effects for each type of snake
(eg. brown, tiger, black snakes etc.), the distribution of bites by these snakes (distribution of the snakes) and the
role and dose of antivenom in each type of snake envenoming.
Expected future outcomes:
The analysis of the randomised controlled trial in the next few months will define the use, risks and benefits of
fresh frozen plasma in snake bite coagulopathy for Australian snakes and will have potential value to the
treatment of snake bite world wide because fresh frozen plasma is more readily available than antivenom.
Name of contact:
Geoff Isbister
Email/Phone no. of contact:
geoff.isbister@gmail.com
NHMRC Research Achievements - SUMMARY
Grant ID: 124331
CIA Name: Prof Peter Rogers
Admin Inst: Monash University
Main RFCD: Obstetrics and Gynaecology
Total funding: $759,928
Start Year: 2000
End Year: 2004
Grant Type: NHMRC Project Grants
Title of research award:
Endometrial angiogenesisEndometrial angiogenesis
Lay Description (from application):
The lining of the uterus is unusual compared to other parts of the adult body in that new blood vessels grow
and then breakdown during menstruation every month. The aim of this project is to understand what controls
the growth and regression of these uterine blood vessels. This information is of immediate relevance to a
number of clinical problems where an ability to either promote or prevent blood vessel growth would be of
major advantage. For example, increased blood vessel growth would accelerate wound healing, while blocking
blood vessel growth would prevent the growth and spread of cancers. Another disorder that could be
controlled through preventing blood vessel growth is endometriosis, a disease where cells from the lining of
the uterus grow inside the abdomen causing pain and infertility. Endometriosis affects upto 10% of women.
Research achievements (from final report):
The primary focus of this research project was to better understand how new blood vessels form in the lining of
the uterus. A fundamental knowledge of uterine blood vessel growth is relevant to a large number of common
women's health problems, including endometriosis, menorrhagia (excessive menstrual blood loss),
breakthrough bleeding (irregular menstrual bleeding associated with hormone replacement therapy and
hormonal contraceptives), endometrial cancer, fibroids, infertility and establishment of a normal placenta
during pregnancy.
Expected future outcomes:
This project has increased fundamental knowledge that underpins our understanding of uterine function in both
normal and diseased states. Future work will build on this knowledge base to develop better treatments and
outcomes for a number of diseases that affect the uterus, including endometriosis, endometrial cancer, fibroids
and inadequate placental function.
Name of contact:
Peter A W Rogers
Email/Phone no. of contact:
Peter.rogers@med.monash.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 180404
CIA Name: Prof James Cooper
Admin Inst: Monash University
Main RFCD: Intensive Care
Total funding: $269,750
Start Year: 2002
End Year: 2006
Grant Type: Established Career Fellowships
Title of research award:
Saline of Albumin Fluid Evaluation (Safe) studySaline of Albumin Fluid Evaluation (Safe) study
Lay Description (from application):
Not Available
Research achievements (from final report):
This Practitioner Fellowship enabled completion and publication of two pivotal multicentre trials testing
resuscitation fluids in critically ill patients. These were published in JAMA and NEJM. A Victorian
collaboration tested prehospital hypertonic saline resuscitation in head injury patients, established that it did not
improve long term patient outcomes, and prevented widespread introduction on Australian ambulances.
Second, an ANZICS Clinical Trials Group (CTG) collaboration (the SAFE trial) found that contrary to
previous research, albumin and saline fluid resuscitation in intensive care patients were equally effective and
safe. This finding enabled practice change in Australia towards increased use of saline - with substantial cost
savings. A substudy from SAFE, also published in NEJM in 2007, found that saline resuscitation was
associated with better survival in head injury - and is changing clinical practice internationally in head injury
patients. , During the Fellowship period, Dr Cooper obtained 5 further new NHMRC project grants for major
clinical trials, and established a new bi-national Intensive Care Research Centre (NHMRC Enabling Grant
funded) at Monash University. He also became Vice-Chair (and currently Chair) of the ANZICS CTG.
Expected future outcomes:
The multicentre clinical trials enabled by the Fellowship have translated to improved management of critically
ill patients internationally. Fluid resuscitation, management of severe head injuries, of septic shock, and
prevention of venous thrombosis have all been improved. The Research Centre will train a new generation of
clinican - researchers in intensive care medicine.
Name of contact:
Prof David J (Jamie) Cooper
Email/Phone no. of contact:
j.cooper@alfred.org.au
NHMRC Research Achievements - SUMMARY
Grant ID: 194242
CIA Name: Dr Lesley Day
Admin Inst: Monash University
Main RFCD: Epidemiology
Total funding: $665,930
Start Year: 2002
End Year: 2005
Grant Type: NHMRC Project Grants
Title of research award:
Risk factors for serious farm-work related injury among adult malesRisk factors for serious farm-work related
injury among adult males
Lay Description (from application):
This study addresses occupational injury among male adult farm workers. The health and safety performance
of agricultural industries is among the worst in Australia. A recently published study of work-related fatalities
from 1989 to 1992 found that rural industries ranked third, with a fatality rate 3-4 times that for all industries.
The rural industries accounted for 80 deaths annually. Best estimates place the cost of farm injury between $0.5
and $1.29 billion per year. This study is designed to contribute to farm injury prevention by: (1) identifying
factors associated with a higher risk of serious injury among adult farm workers and (2) determining the
proportions of the farm workforce who are exposed to various injury risks. The study will recruit 300 seriously
injured or killed farm workers from regional Victoria and collect information about themselves, their working
life and the property on which they work. This information will be compared with 600 randomly selected farm
workers who are not seriously injured to determine which personal, work and environmental factors place farm
workers at higher risk of injury. The study will lead to the development of new or more refined prevention
strategies and programs. A study of this kind has not been conducted before in Australia and would contribute
to a continuing scientific basis for selection of interventions for farm injury and targeting of prevention
programs, at a time of increasing momentum in agricultural health and safety.
Research achievements (from final report):
This study has led to a greater understanding of the factors leading to farm injury which is required to underpin
the development of new or more refined intervention strategies. For example, we found that although owners
and managers comprise the greater proportion of injury farmers, employees and contractors were at increased
risk of injury. A greater understanding of the individual and farm characteristics associated with an increased
risk of farm injury is likely to lead to better targeting of prevention programs. A study of this kind has not been
conducted before in Australia and will provide a continuing scientific basis for selection of interventions for
farm injury and targeting for prevention programs, at a time of increasing momentum in agricultural health and
safety.
Expected future outcomes:
If the study results are used to inform prevention programs, the expected future outcome is a decrease in the
rates of serious farm work related injury among men in Australia.
Name of contact:
Lesley Day
Email/Phone no. of contact:
lesley.day@muarc.monash.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 194272
CIA Name: Prof David Morgan
Admin Inst: Monash University
Main RFCD: Biomechanics
Total funding: $196,410
Start Year: 2002
End Year: 2004
Grant Type: NHMRC Project Grants
Title of research award:
Adaptation of muscle to eccentric exercise and its clinical applications 194272Adaptation of muscle to
eccentric exercise and its clinical applications 194272
Lay Description (from application):
Work in this laboratory has concentrated on Delayed Onset Muscle Soreness (DOMS), the soreness felt for
several days after unaccustomed exercise. This is particularly so when the exercise involves stretching of
active muscle, called eccentric exercise, at longer muscle lengths. DOMS is due to microscopic muscle
damage. A rapid training effect, leading to reduced soreness from a subsequent bout of similar exercise, has
been identified by us as due to a specific structural adaptation. This results in the optimum length for tension
generation moving to longer muscle length so that the muscle is less likely to be damaged during subsequent
stretches. Hypothesizing that gross muscle tears arise from the microscopic damage, we have begun
investigating whether eccentric exercise training can prevent hamstring muscle injuries. We have shown that
eccentric exercise shifts the optimum length for contraction in human hamstring muscles. We are now
examining athletes with past injuries, known to be likely to re-injure. Other experiments are designed to show
that sports that cause injury do indeed include eccentric exercise of the hamstring muscles. We are also
investigating the effectiveness of eccentric exercise in treating apparently normal children who compulsively
walk on their toes. We have built monitoring equipment and are monitoring both conventional and exercise
based treatments designed to shift muscle optimum length to longer lengths to allow the children to place their
heels on the ground. Finally, most muscles contain different fibre types, distinguished mainly by their speed of
contraction. It has been suggested that they are not all uniformly susceptible to damage from eccentric exercise,
a result not predicted by our theory. However, we hypothesize that secondary factors, particularly the length for
generating optimum tension, may be responsible for these differences. We plan to test this idea by measuring
properties of different types of motor units.
Research achievements (from final report):
N/A
Expected future outcomes:
The eccentric exercise program for the idiopathic toewalkers has formed the backbone of a highly successful
management program that will be promoted to health professionals around the world., Extending better
understanding of how to perform eccentric exercises without risk of injury or excessive soreness is expected to
result in an increased usage for injury prevention.
Name of contact:
David Morgan
Email/Phone no. of contact:
David.Morgan@ieee.org
NHMRC Research Achievements - SUMMARY
Grant ID: 194417
Start Year: 2002
CIA Name: Prof Rachelle Buchbinder
End Year: 2004
Admin Inst: Monash University
Grant Type: NHMRC Project Grants
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $269,020
Title of research award:
Efficacy of physiotherapy after hydrodilatation for the painful stiff shoulder: a randomised placebo-controlled
trialEfficacy of physiotherapy after hydrodilatation for the painful stiff shoulder: a randomised placebocontrolled trial
Lay Description (from application):
Shoulder disorders are common, being third only to back and neck complaints as musculoskeletal reasons for
medical consultation and they account for 10% of all physiotherapy referrals. The stiff painful shoulder affects
up to 2-5% of the general population, being more common in middle age and diabetes. It causes significant
pain and disability that restricts activities of daily living as well as work and leisure. Forty percent of sufferers
will continue to have symptoms and restricted movements beyond 3 years and 15% will have persistent
disability. Because this disease is prevalent, it imposes a considerable burden on the Australian health care
system. Shoulder hydrodilatation is a common conservative treatment option that has been shown by our
research group to have short-term but not long-term benefits. Physiotherapy may be prescribed following
hydrodilatation on the basis that it may maintain the initial benefits seen with hydrodilatation. However, there
are no studies to either support or refute this hypothesis. Thus, this novel research project will answer
important questions about the efficacy of a physiotherapy program in addition to hydrodilatation for the stiff
painful shoulder. We will determine whether physiotherapy offers a benefit over hydrodilatation alone and if
so, whether this benefit is sustained. In addition we will determine whether the additional costs of
physiotherapy represent good value for money. The results of this project can then be easily and immediately
translated into clinical practice as recommendations can be made about the usefulness of physiotherapy for this
patient population. The results will be of major benefit not just to the physiotherapy profession but to the
medical profession who must justify patient referral to physiotherapy.
Research achievements (from final report):
This research project will answer important questions about efficacy of a physiotherapy program in addition to
hydrodilatation for the stiff painful shoulder. Our trial will determine whether physiotherapy offers a benefit
over hydrodilatation alone and if so, whether this benefit is sustained. The standardised physiotherapy we
developed can be taught to physiotherapists. In addition, if there is a benefit, it will show whether the
additional costs of physiotherapy represent good value for money. Our results will be able to be immediately
translated into clinical practice since we will be able to make recommendations about the usefulness of
physiotherapy for this patient population. The results will be of major benefit not just to the physiotherapy
profession but to the medical profession who must justify patient referral to physiotherapy.
Expected future outcomes:
The results of our study will be widely disseminated to ensure timely take up of the findings into clinical
practice. We expect to do this via publications, presentations and by updating our Cochrane systematic review
of physiotherapy for shoulder pain. The results will also be used to inform our future research agenda in terms
of finding effective treatments for shoulder pain.
Name of contact:
Rachelle Buchbinder
Email/Phone no. of contact:
rachelle.buchbinder@med.monash.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 236858
CIA Name: Prof Julian Rood
Admin Inst: Monash University
Main RFCD: Medical Bacteriology
Total funding: $78,500
Start Year: 2003
End Year: 2003
Grant Type: NHMRC Project Grants
Title of research award:
Two-component regulatory systems involved in toxin production in Clostridium perfringensTwo-component
regulatory systems involved in toxin production in Clostridium perfringens
Lay Description (from application):
The bacterium studied in this project causes gas gangrene, a severe and often fatal infection of traumatic or
surgical wounds. The project involves the detailed analysis of the process by which this bacterium controls the
production of the toxic proteins that are required for disease to occur. The emphasis is to determine the
mechanism by which this regulatory process is mediated. Research in this laboratory has identified two genes
whose protein products are the key links in this regulatory network. The objectives of the project will be to
determine which part of the regulatory protein interacts with the target toxin gene, to start to determine the
structure of the regulatory protein so that the precise biochemical mechanism of action can be ascertained, to
determine the components of the DNA target that are essential for binding activity, and to identify other genes
that are involved in the regulation of both the toxin genes and other genes that may be implicated in the disease
process. These studies will be facilitated by the availability of the complete genome sequence of this
pathogenic bacterium. The project will make a major contribution to our knowledge of how bacteria that cause
disease are able to control the production of the toxins that are critical to the disease process. If we are to learn
how to more effectively control and treat bacterial infections then it is very important that we understand the
complex regulatory networks that tell bacteria when to produce its disease-causing products.
Research achievements (from final report):
These studies will involve a bacterium that causes gas gangrene by invading a wound, growing and producing
potent toxins. The future directions of this research predominantly involve the elucidation of the precise
mechanism by which two proteins combine to transmit an environmental cell signal into increased production
of the protein toxins that are important in this disease. Specifically, these studies will concentrate on the protein
to protein interactions between each element of this important regulatory cascade. Determination of the crystal
structure of one of these proteins will be an important part of this process. Using this knowledge, we may be in
a better position to develop novel methods of antimicrobial treatment.
Expected future outcomes:
N/A
Name of contact:
N/A
Email/Phone no. of contact:
N/A
NHMRC Research Achievements - SUMMARY
Grant ID: 236859
CIA Name: Prof Julian Rood
Admin Inst: Monash University
Main RFCD: Medical Bacteriology
Total funding: $136,750
Start Year: 2003
End Year: 2003
Grant Type: NHMRC Project Grants
Title of research award:
Pathogenesis of clostridial myonecrosisPathogenesis of clostridial myonecrosis
Lay Description (from application):
The aim of this project is to provide a better understanding of the mechanisms underlying the development of
gas gangrene, an often fatal disease of particular significance to elderly and diabetic patients, who are
particularly susceptible following injury, or surgery, or in some cases when suffering from colon cancer.
Although research has been carried out on this disease for many years prompt surgical removal of the infected
tissue, often including amputation of a limb, is still commonly used to ensure the patient's survival. This project
involves the study of the two bacteria that are the major causes of the disease. We aim to find out how the
bacteria mediate the disease, in particular to determine which toxic factors produced by the bacteria are
involved. The normal host response to a bacterial infection is a rapid influx of white blood cells to the infected
tissue, which is part of the normal inflammatory response. These cells engulf and degrade the bacteria, clearing
the infection. However, a major characteristic of gas gangrene pathology is that very few white blood cells
infiltrate the infected tissue. We aim to determine why the host fails to mount an inflammatory response to this
bacterial infection. We will achieve this objective by developing a better understanding of the role of the
bacterial toxins in the development of this morbid disease. It is hoped the results from this study will enable the
development of more effective therapeutic and prophylactic treatments for this disease and also provide a
foundation for studies into the modulation of the host response by other bacterial species.
Research achievements (from final report):
The research will continue as originally proposed with a focus on elucidating the mechanism by which
pathogenic bacteria can mediate gas gangrene, an often fatal disease of particular significance to the elderly or
to diabetics. These patients are particularly susceptible following injury, or surgery, or in some cases when
suffering from colon cancer. Continued studies will aim to determine how the toxic factors produced by the
bacteria are involved in the disease process. The normal host response to a bacterial infection is a rapid influx
of white blood cells to the infected tissue, which is part of the normal inflammatory response. These cells
engulf and degrade the bacteria, clearing the infection. However, a major characteristic of gas gangrene
pathology is that very few white blood cells infiltrate the infected tissue. Further studies will determine why the
host fails to mount an inflammatory response to this bacterial infection. It is hoped that the results from this
study will enable the development of more effective therapeutic and prophylactic treatments for this disease
and also provide a foundation for studies into the modulation of the host response by other bacterial species.
Expected future outcomes:
N/A
Name of contact:
N/A
Email/Phone no. of contact:
N/A
NHMRC Research Achievements - SUMMARY
Grant ID: 236880
CIA Name: Dr Lesley Day
Admin Inst: Monash University
Main RFCD: Epidemiology
Total funding: $706,500
Start Year: 2003
End Year: 2009
Grant Type: Established Career Fellowships
Title of research award:
Application of epidemiological methods to injury prevention researchApplication of epidemiological methods
to injury prevention research
Lay Description (from application):
Not Available
Research achievements (from final report):
This Fellowship supported a program of injury research directed towards two high risk populations- the farm
workforce, and older people. Key achievements in the farm safety area include the development of a tractor
safety rating system (STARS), the evaluation of guidelines for the retrofitting of safe access platforms for the
prevention of tractor run-over injuries, and the identification of novel risk factors for serious farm work related
injury. These three projects provide evidence to underpin prevention programs. The uptake of STARS and the
guidelines for retrofitting safe access platforms would contribute to the reduction of the two leading causes of
tractor related fatalities. The identification of being an employee or contractor, not having attended farm
training courses, and machinery age as risk factors for serious farm work related injury provides direction for
strategic prevention programs. The key achievements in the area of older persons' falls prevention included the
testing to two popular falls interventions - tai chi, and a multifactorial risk factor referral program- neither of
which were found to be effective in the groups in which they were tested. A train the trainer package for the
NoFalls Exercise Program, shown to be effective in previous research, was developed and 100 trainers, and
500 exercise class leaders were trained across Australia. In addition, modelling of the impact of proven falls
interventions if delivered at the population level provides a foundation for decision making regarding public
investment in falls prevention programs.
Expected future outcomes:
Falls among older people, and the associated functional decline and injury, is a major challenge to the health
and quality of life of our ageing population. The work of the Fellowship in testing falls interventions,
supporting ongoing delivery of a successful falls intervention, and policy modelling, will continue to inform
policy and practice in this area.
Name of contact:
Lesley Day
Email/Phone no. of contact:
lesley.day@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 237024
CIA Name: Dr Belinda Gabbe
Admin Inst: Monash University
Main RFCD: Epidemiology
Total funding: $261,500
Start Year: 2003
End Year: 2006
Grant Type: Early Career Fellowships (Australia)
Title of research award:
Outcomes of major trauma and sports injuriesOutcomes of major trauma and sports injuries
Lay Description (from application):
Not Available
Research achievements (from final report):
Traumatic injury remains a leading cause of the global burden of disease. Reducing the burden of injury
remains a priority public health issue and requires detailed knowledge of its incidence and outcomes. The most
commonly used outcome measure in injury is the mortality rate. However, the vast majority of injured people
survive. The percentage of preventable deaths is now very low with improvements in trauma care increasing
the probability of surviving even severe injuries. This has placed a greater emphasis on determining the
morbidity associated with injury and, in particular, establishing the degree of functional loss, ongoing disability
and lost quality of life experienced by survivors. Despite acknowledgement that the greatest cost burden of
injury exists in these aspects of morbidity, routine measurement of injury outcomes other than mortality is rare,
particularly in Australia. Trauma registries, like other disease registries, provide the basis for monitoring the
incidence and outcomes of injury but have been under-utilised with respect to measuring outcomes other than
mortality. The research undertaken during this fellowship focused primarily on establishing the needs of
trauma registries with respect to outcomes measurement, evaluating existing measures of functional outcome
and implementing functional and quality of life measures into the population-based Victorian State Trauma
Registry and the Victorian Orthopaedic Trauma Outcomes Registry. The routine monitoring of post-hospital
discharge outcomes will enable monitoring of trauma outcomes over time, the identification of sub-groups of
injury at higher risk of poor outcomes, and provide the information necessary to drive improvements in trauma
care.
Expected future outcomes:
The future outcomes of this research will be ongoing monitoring of the long term outcomes following injury,
an improved understanding of the burden of injury, and the ability to inform trauma care policy, delivery and
injury prevention research in order to reduce the public health burden of injury
Name of contact:
Belinda Gabbe
Email/Phone no. of contact:
belinda.gabbe@med.monash.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 284278
CIA Name: Prof Uwe Proske
Admin Inst: Monash University
Main RFCD: Central Nervous System
Total funding: $287,250
Start Year: 2004
End Year: 2006
Grant Type: NHMRC Project Grants
Title of research award:
Changes in motor control and kinaesthetic sensations after eccentric exercise.Changes in motor control and
kinaesthetic sensations after eccentric exercise.
Lay Description (from application):
It is a well-known observation that after a period of intense exercise we are unsteady on our feet and are
clumsy when attempting to make precision movements. Such impressions are particularly marked after
eccentric exercise, during which the contracting muscles are forcibly lengthened. Activities such as walking
downhill, skiing and horse riding involve eccentric exercise. The debilitating consequences of this kind of
exercise are attributed, not just to the post-exercise effects of fatigue, but to loss of muscle force from damage
to fibres. Eccentric exercise also leads to longer term effects. The breakdown of the damaged tissue leads to
sensations of stiffness and soreness the next day. This application proposes experiments aimed at studying a
number of effects of eccentric exercise on motor control, and establishing the muscle, spinal and brain levels
at which they occur. Three studies are planned. In the first, the question will be explored whether we are less
able to use the motor areas of our brains to execute voluntary contractions after exercise. So fatigue is not
just a matter of exhausted muscles but perhaps also exhausted brains. We will use brain and spinal cord
stimulation to explore this point. Then we plan to listen to single motor units, the basic elements of muscle
control, to try to understand the mechanism by which the brain minimises the debilitating effects of fatigue.
Finally we want to examine subjects' ability to locate their limbs in space as a means of providing a basis for
the clumsiness we experience after intense exercise. These are all important issues relevant to clinical
medicine and rehabilitation as well as sports science and exercise.
Research achievements (from final report):
We have studied human position and movement sense in a number of ways and obtained significant new data.
When in an arm-matching task one arm is loaded with a heavy weight, the blindfolded subject is able to match
its position just as accurately as they did with the unloaded arm. When one arm was exercised to fatigue, this
disturbed the subject's ability to match the positions of their two arms. The degree of disturbance was
correlated with the level of fatigue. Matching errors suggested that subjects perceived their fatigued muscles to
be longer than they actually were. These findings are unexpected and they compliment earlier observations on
the paralysed anaesthetised hand. Clearly mechanisms within the brain are involved in determining arm
position when the arm muscles are active, as in bearing a load. Such a conclusion represents a major shift in
present-day thinking in this area. It has implications for the interpretation of the neural basis of certain
neurological conditions such as schizophrenia and Parkinson's disease.
Expected future outcomes:
Important implications of this work relate to the effects of fatigue in sport and exercise. A fatigued athlete can
be uncertain of the position of their limbs if they are not expressly looking at them. The effects of exercise in
disturbing proprioception also has implications for the elderly. Proprioception is an important indicator of the
risk of falls in the elderly.
Name of contact:
Uwe Proske
Email/Phone no. of contact:
uwe.proske@med.monash.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 284345
Start Year: 2004
CIA Name: A/Pr Stephen Bernard
End Year: 2006
Admin Inst: Monash University
Grant Type: NHMRC Project Grants
Main RFCD: Medical and Health Sciences not elsewhere classified
Total funding: $311,000
Title of research award:
A trial of prehospital rapid sequence intubation in patients with severe head injuryA trial of prehospital rapid
sequence intubation in patients with severe head injury
Lay Description (from application):
In Australia, major trauma is a leading cause of death in people between the ages of one and 44 years. In
addition to mortality, there is a high morbidity rate and quality adjusted life-years lost from injury is vast. In
broad terms, major trauma is defined as those injuries with the highest severity, requiring time critical medical
care. Over 10% of major trauma patients have a severe head injury and approximately 40% of these patients
die and another 40% have significant long-term morbidity. Following severe head injury, it is common for
patients to have decreased oxygen levels and this is associated with a significant increase in brain damage. To
prevent or treat this, patients with severe head injury require endotracheal intubation (a tube is placed in the
airway to provide oxygen to the patient) as soon as possible following injury. However, in most patients with
severe head injury, endotracheal intubation requires the use of drugs to facilitate placement of the endotracheal
tube. The usual technique involves the administration of both a sedative drug and an appropriate musclerelaxant. This technique is known as rapid sequence intubation (RSI). However, it is unknown whether RSI
should be undertaken by paramedics early after injury or be delayed until arrival at the hospital. Since better
evidence of improved outcome is required to justify the possible risk and considerable expense of training
ambulance paramedics in the skill of RSI, it is proposed that a randomized, controlled trial of RSI in adults
with severe head injury be conducted. This trial will compare rapid sequence intubation with standard airway
management (no intubation) by ambulance paramedics for major trauma patients with severe head injury. This
study will assess differences in patient outcome at 6-months post injury. The study will involve head injury
patients treated by paramedics in Victoria.
Research achievements (from final report):
This clinical trial enrolled 312 patients. It was found that paramedic rapid sequence intubation is associated
with an increase in favorable outcomes from 31% to 46% at 6 months post injury.
Expected future outcomes:
It is proposed that mild hypothermia might be induced after intubation to improve neurological outcomes after
severe head injury
Name of contact:
A/Prof Stephen Bernard
Email/Phone no. of contact:
stephen.bernard@alfred.org.au
NHMRC Research Achievements - SUMMARY
Grant ID: 284354
CIA Name: Prof Rachelle Buchbinder
Admin Inst: Monash University
Main RFCD: Endocrinology
Total funding: $586,250
Start Year: 2004
End Year: 2007
Grant Type: NHMRC Project Grants
Title of research award:
Efficacy and safety of vertebroplasty for treatment of painful osteoporotic spinal fractures: a randomised
trialEfficacy and safety of vertebroplasty for treatment of painful osteoporotic spinal fractures: a randomised
trial
Lay Description (from application):
Painful spinal or vertebral fractures are a substantial and growing public health problem and are a burden on
the health care system. In Australia, 20-25% of women and 15-20% of men over the age of 50 will develop one
or more fractures of their spine in their lifetime. Up to a half of these fractures will result in severe pain and
disability. While the fractures generally heal within weeks or a few months, some are so painful that they
require narcotic pain control, hospitalisation, and/or long-term nursing home care. Other problems include
chronic pain, spinal deformities, loss of height and mobility and restricted breathing. Vertebroplasty is a new
procedure consisting of injection of a type of 'bone cement' into the vertebrae to mend the break. It is an
exciting treatment because for some people, this results in an immediate and sustained improvement in pain.
Although rare, complications such as rib fracture, cement leakage and fractures in other vertebrae do occur.
One particular concern is that the mechanical changes to the spine caused by the bone cement may cause longterm complications such as an increased risk of future fractures of treated or adjacent vertebrae. So far, there is
very little evidence of the efficacy and safety of this new technology. Importantly, it has not been compared
with usual medical care for fractures. In medical research it can be difficult to properly evaluate an exciting and
'apparently' effective treatment that doctors and patients demand. The main aim of this project is to determine
whether vertebroplasty is an effective and safe treatment compared to usual medical care. We have a unique
opportunity to evaluate vertebroplasty through a strong collaborative effort between the 3 centres currently
offering this procedure in Melbourne. If vertebroplasty can be demonstrated to be an effective, safe and costeffective treatment for painful osteoporotic spinal fractures this will be a valuable addition to current treatment
options.
Research achievements (from final report):
Painful vertebral fractures complicating osteoporosis are a substantial and growing public health problem
leading to severe morbidity and an increased burden on the health care system. Vertebroplasty is becoming an
increasingly accepted treatment for vertebral fractures despite the lack of scientific evidence of its benefit. The
outcome of our proposed research will be to establish whether vertebroplasty is efficacious, safe, and costeffective compared to placebo for painful osteoporotic spinal fractures. If positive, we will have scientific
evidence to support the currently uncorroborated widespread endorsement of this intervention. If, on the other
hand, our results indicate that its efficacy is no greater than placebo (and it may do more harm), then the
resources spent on performing these procedures might be put to better use. We have published an editorial
outlining our concerns about use of vertebroplasty without high quality evidence of its benefit.
Expected future outcomes:
We will determine the short term efficacy and safety of vertebroplasty for alleviating pain and improving
function for acute painful osteoporotic vertebral fractures and examine if there is excess risk of further
vertebral fractures within two years.
Name of contact:
Professor Rachelle Buchbinder
Email/Phone no. of contact:
rachelle.buchbinder@med.monash.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 284402
CIA Name: Dr Donna Urquhart
Admin Inst: Monash University
Main RFCD: Orthopaedics
Total funding: $268,650
Start Year: 2004
End Year: 2008
Grant Type: Early Career Fellowships (Australia)
Title of research award:
The characterisation of orthopedica trauma and the evaluation of outcomeThe characterisation of orthopedica
trauma and the evaluation of outcome
Lay Description (from application):
Not Available
Research achievements (from final report):
Musculoskeletal conditions are major contributors to pain and disability in Australia, with more than 6.1
million people affected. Moreover, with aging of the population and the obesity epidemic, these figures are
expected to rise. As a result, musculoskeletal conditions have been declared a National Health Priority. This
research program was aimed at investigating risk factors, outcomes and treatment strategies for
musculoskeletal conditions, including the two most common muscloskeletal conditions, low back pain and
osteoarthritis. , Some of the key findings from our research program included; identifying that both high levels
of back pain and disability are associated with obesity in community-based women and that while knee
malalignment is associated with progression of knee osteoarthritis, there is insufficient evidence to support a
relationship with the development of this condition. With respect to outcomes, we found a large percentage of
patients after musculoskeletal injury have ongoing pain and disability and a reduced capacity to return to work
6 months after their trauma and that partial and revision hip replacements are resource intensive for the public
and private health-care systems, respectively. Moreover, we found that there is no clear evidence to support the
use of two common treatment strategies, anti-depressants and radiofrequency deinnervation, for the
management of low back pain. , This work has the potential to guide health and medical researchers in future
epidemiological research into low back pain and osteoarthritis, inform health services in the outcomes and
resource utilisation associated with these conditions, and assist clinicians in the selection of treatment strategies
in the management of musculoskeletal pain and disability. Ultimately, the findings of this research program
will assist in the future development of innovative strategies to prevent and manage chronic pain and disability
associated with musculoskeletal conditions.
Expected future outcomes:
The findings of this research program will assist in the future development of innovative strategies to prevent
and manage chronic pain and disability associated with musculoskeletal conditions.
Name of contact:
Donna Urquhart
Email/Phone no. of contact:
Donna.Urquhart@med.monash.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 299950
CIA Name: Prof Lenore Manderson
Admin Inst: Monash University
Main RFCD: Care for Disabled
Total funding: $251,743
Start Year: 2004
End Year: 2007
Grant Type: NHMRC Project Grants
Title of research award:
Social aspects of amputation among an aging population in urban and rural VictoriaSocial aspects of
amputation among an aging population in urban and rural Victoria
Lay Description (from application):
In recent years, social scientists have shown increasing interest in how individual and social structural factors
inter-relate to produce wellbeing. An associated interest has been the role of social networks and social support
for individuals with chronic disease, enabling them to manage ongoing illness or impairment, live fulfilling
lives and experience wellbeing. To explore these issues in an Australian context, this project focuses on people
who have had amputations from trauma, advanced disease (e.g. cancer) or complications of chronic disease
(e.g. diabetes). The study aims to increase our understanding of how people live with particular diseases and
health conditions, the impact of these conditions on body image, self-esteem, social relationships and societal
participation, and how structural, contextual and environmental factors affect individual functioning and
disability. By including people of different gender, ethnicity, age and area of residence, the study is concerned
with how life circumstances and socialization (including ideas of gender) influence outcome. The findings will
contribute to our knowledge of adaptation and provide information relevant to improved care for people from
different backgrounds. The study is significant because of the increase in chronic disease (relative to infectious
disease) in contemporary industrialised societies, particularly with an aging population. The policy context of
this work is government interest in maximising the independence and wellbeing of people who are aged and/or
with chronic disease, while minimising the economic costs. The research is also significant to international
agencies and consumer organisations concerned with reducing discrimination against and inequality of people
with impairments. The study will contribute to the WHO classification of disability, and efforts to promote and
protect the rights and dignity of persons with disabilities.
Research achievements (from final report):
This research explored social and psycho-social factors impacting upon an individual's adaptation to lower
limb amputation, with a particular focus on health service delivery. Data highlighted the importance of
providing formal psycho-social support during the in-patient rehabilitation phase to assist patients with their
experiences of grief and loss, such as from a psychologist. Currently, rehabilitation services tend to provide
services to people at high risk of developing mental health co-morbidities only; this data suggested that many
recent amputees experience sub-clinical levels of mental illness, particularly depression. The process of
adaptation to amputation would be enhanced by such support services, which may reduce the incidence of
future mental health problems. Findings have also assisted in the establishment and maintenance of the
condition-specific peer support group, limbs4life, including material on life post-amputation.
Expected future outcomes:
Data will be used to inform future service delivery models and provide an assessment about the efficacy of the
rehabilitation process. In-depth knowledge about the processes of adaptation will be used to shape program
development and assist in community rehabilitation and lay condition-specific models of social support.
Name of contact:
Narelle Warren
Email/Phone no. of contact:
Narelle.Warren@med.monash.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 314502
CIA Name: Prof James Cooper
Admin Inst: Monash University
Main RFCD: Intensive Care
Total funding: $490,500
Start Year: 2005
End Year: 2007
Grant Type: NHMRC Project Grants
Title of research award:
Multi-centre randomised trial of early decompressive craniectomy in patients with severe traumatic brain
injuryMulti-centre randomised trial of early decompressive craniectomy in patients with severe traumatic brain
injury
Lay Description (from application):
Despite optimal neurosurgical and intensive care therapy, many trauma patients with severe brain injury
(typically young males) have very poor long term neurological outcomes. Current knowledge suggests that a
key contributor to secondary brain damage which occurs after injury and to poor neurological outcomes is
brain swelling and subsequent increase in brain pressure. Present intensive care therapies to control brain
pressure are often not effective, and favourable neurological outcomes occur in only 20-30% of these patients.
Small studies suggest that a surgical operation called decompressive craniectomy (DC) may decrease brain
pressure and improve neurological outcomes in these patients. DC involves temporarily surgically removing
a piece of skull bone (during the swelling period) and replacing it when the swelling has subsided. DC is done
under general anaesthetic in unconscious patients and is used occasionally at present, although due to
insufficient research the benefits are controversial. The proposed study is a multi-centre randomised
controlled study of best current therapies plus early decompressive craniectomy vs best current therapies alone
in selected unconscious patients with severe head injury. The study outcome is patient neurological function
measured 6 months after the injury. A study of this type is required before early DC could become a routine
therapy in Australia. Next of kin will sign informed consent for the study and then also for the surgery if
patients are randomised to surgery. The study will be managed at the Alfred Hospital/Monash University in
Melbourne and includes fifteen collaborating ANZ neurotrauma centres over 3.0 years. There are >200
patients in Australia annually in this category with potential for DC to increase favourable outcomes in >40
patients annually. Lifetime costs for these patients with severe disability are > $2.4 million, so there may be
substantial economic and social impact.
Research achievements (from final report):
Traumatic brain injury is a potentially devasting injury that predominantly affects young males. Approximately
10% of patients admitted with severe traumatic brain injury have a diffuse injury and persistent brain swelling
that is difficult to control with best medical managment. Over the past decade, mangement of these patients has
been shifting from barbiturate coma to decompressive craniectomy. This is a well established neurosurgical
procedure in which a large piece of skull bone is removed, stored for 1-2 months and then replaced.This project
(NEJM 2011; 364:1493-1502) assessed for the first time in adults the effectiveness of this procedure. Patients
with severe diffuse traumatic brain injury that were suitable for the project were randomly assigned to receive
best medical care or decompressive craniectomy and best medical care. The results showed that surgery was
extremely effective in decreasing intracranial pressure (a measure of brain swelling), markedly decreased
medical therapies required for treatment of intracranial pressure, shortened ventilation time and shortened
length of stay in ICU.However despite these positive short term effects, the findings in relation to patient's
functional outcome at 6 months were the reverse of what was expected. The group of patients who received
surgery were more likely to have a poorer outcome (death or dependent) compared to those who received best
medical care. These results have enormous significance as the functional outcomes of future patients with
severe diffuse traumatic brain injury can be substantiallyimproved by choosing best medical care rather than
decompressive craniectomy for management of raised intracranial pressure.
Expected future outcomes:
Further analysis of results will provide additional information about the use of decompressive craniectomy in
certain sub groups of patients.
NHMRC Research Achievements - SUMMARY
Name of contact:
Prof Jamie Cooper
Email/Phone no. of contact:
Jamie.cooper@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 334002
Start Year: 2005
CIA Name: Prof Jennie Ponsford
End Year: 2007
Admin Inst: Monash University
Grant Type: NHMRC Project Grants
Main RFCD: Neurosciences not elsewhere classified
Total funding: $328,050
Title of research award:
Fatigue, attention and sleep disturbance after traumatic brain injuryFatigue, attention and sleep disturbance
after traumatic brain injury
Lay Description (from application):
Traumatic brain injury (TBI) is a major cause of disability in young people. A major obstacle to the
rehabilitation of these young people and their return to work or study is their susceptibility to fatigue postinjury. Sleep disturbance is also often reported following TBI and this may accentuate fatigue. Suprisingly,
little research has been conducted on the nature, causes or progression of fatigue and sleep disorders following
TBI and their possible interrelationships. This study aims to investigate the incidence and extent of fatigue in a
large group of people who have experienced a TBI compared to a control group, how fatigue changes over time
and its impact on daily life. The study will also address whether higher fatigue levels are associated with
decreased attention and speed of information processing. Changes in sleep patterns will also be investigated
using both subjective measures, such as sleep quality and daytime sleepiness, and objective physiological
measures, such as the time of dim light melatonin onset and polysomnography, comparing the head injured
group with controls. The interrelationships between fatigue and sleep changes will then be examined and also
their association with injury severity, the location of the brain injury, the time since the injury, age, the
presence of any cognitive impairments and the incidence of depression. The project has the potential to
provide valuable information to healthcare professionals on the diagnosis of fatigue and sleep disorders in head
injury patients. The investigation of the nature, causes and impact of fatigue and sleep disorders could also
provide a basis for therapy. For example, fatigue and problems with attention and slowed information
processing can be minimized by restructuring lifestyle demands and simple and effective treatments are
available for many sleep disturbances, such as bright light therapy and/or exogenous melatonin.
Research achievements (from final report):
This project has provided valuable information to health care professionals about fatigue and sleep changes
following TBI, whilst also providing information as to which assessment tool/s best identify fatigue and sleep
disturbances following TBI. The identification of an association between fatigue and deficits of attention and
speed of information processing has provided a basis for structuring lifestyle demands to minimize demands on
these processes and thereby minimize fatigue. An association was also identified between depression and
fatigue, highlighting the fact that if depression is treated appropriately, then fatigue might also be alleviated.
Examining the nature and extent of sleep disturbances has highlighted the need for the development of
treatments for daytime somnolence, a further source of fatigue, debilitation, and reduced feeling of wellbeing
following TBI. Simple and effective treatments are available for many sleep disturbances. For example where
changes in the circadian system are demonstrated, bright light therapy and/or exogenous melatonin may be
administered.
Expected future outcomes:
On the basis of these study findings, we have now developed a proposal for an intervention study to alleviate
fatigue, daytime sleepiness and sleep disturbance, comparing the effectiveness of cognitive behaviour therapy,
and/or light therapy with treatment as usual.
Name of contact:
Professor Jennie Ponsford
Email/Phone no. of contact:
jennie.ponsford@med.monash.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 334010
CIA Name: Prof Rachelle Buchbinder
Admin Inst: Monash University
Main RFCD: Rheumatology and Arthritis
Total funding: $404,425
Start Year: 2005
End Year: 2009
Grant Type: Established Career Fellowships
Title of research award:
Practitioner FellowshipPractitioner Fellowship
Lay Description (from application):
Not Available
Research achievements (from final report):
The achievements of this research award have included the completion of several randomised controlled trials
that I have led including an important study investigating the value of vertebroplasty (an injection of bone
cement) for painful spinal fractures due to osteoporosis that has been increasingly used despite a lack of strong
evidence supporting its use. Not only did this trial fail to demonstrate significant benefits for vertebroplasty
compared to a sham procedure, it was also widely cited as exemplifying the dangers of adopting new
treatments into routine clinical pracice before they have been properly evaluated. The results of the completed
trials are all immediately implementable into clinical practice and have the potential to improve health
outcomes. Another achievement of this award has been the involvement I have had with other colleagues in
establishing the Australian Rheumatology Association Database (ARAD), a highly productive and valuable
resource that is providing important information about the long-term benefits and risks of the newly available
biological drugs for inflammatory arthritis sufferers in Australia. This research award has made it possible for
me to expand my activities related to my role as Joint Coordinating Editor of the Cochrane Musculoskeletal
Group with the completion of many new revews. Together with my linguistic colleagues I have also developed
a novel linguistic framework for improving the quality of written patient materials about medication, and
together with other colleagues I have also established a program of research in the field of health literacy.
Expected future outcomes:
The expected future outcomes of my work include improvements in evidence-informed management of various
musculoskeletal conditions, clarification of the long-term benefits and risks of exposure to biological drugs for
inflammatory arthritis, improvements in written patient information and recognition of the importance of health
literacy to good health.
Name of contact:
Rachelle Buchbinder
Email/Phone no. of contact:
rachelle.buchbinder@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 334060
CIA Name: Prof Sally Green
Admin Inst: Monash University
Main RFCD: Primary Health Care
Total funding: $426,000
Start Year: 2005
End Year: 2007
Grant Type: NHMRC Project Grants
Title of research award:
Implementing Clinical Practice Guidelines in General Practice: A Cluster Randomised Controlled
TrialImplementing Clinical Practice Guidelines in General Practice: A Cluster Randomised Controlled Trial
Lay Description (from application):
Evidence based clinical practice guidelines have the potential to improve clinical practice through providing
health care workers with the most reliable information on which to base their treatment decisions. Many
governments and organisations are investing significantly in the development of guidelines for common and
important clinical disorders. To date, however, we do not fully understand how to increase the uptake of
guidelines and facilitate health care workers to change their practice in line with the guideline's
recommendations. This project aims to work with general practitioners to develop a method or strategy to
increase the uptake of guidelines for the treatment of acute low back pain, particularly to reduce the number of
patients who are unnecessarily x-rayed, and to increase advice to stay active. The effectiveness of the
developed strategy will be tested by randomly assigning general practice clinics to either receive the
intervention or to have access to the guidelines without any extra interventions (such as training and reminders)
to help doctors change their practice. Both the doctor's practice, and patient outcomes of pain and disability
will be measured to determine not only if the doctors followed the guidelines, but whether this resulted in an
improvement in patient outcome. The findings of this study will help us understand the best ways to improve
adhesion to guidelines and so has the potential to be applied to other conditions presenting to general practice
where there are recommendations not currently being implemented into practice.
Research achievements (from final report):
This project evaluated an intervention designed to assist general practitioners better manage people with acute
low-back pain. The study has shown that the GPs who received the intervention intended to order less x-rays
and intended to give advice to stay active more often to their patients with acute low-back pain., , This research
has led to further articulation of the complexities of this kind of research that aims to improve clinical practice,
and has thus furthered understanding in the field of implementation science. This project has also extended the
methodology of the development of theory-based complex interventions, and the assessment of complex
intervention fidelity. Also, this project will inform healthcare policy by providing some answers about the
implementation of guidelines in general practice. Finally, the project has strengthened partnerships between the
Australian-based project team and international colleagues.
Expected future outcomes:
GPs ordering less x-rays for patients with acute low-back pain can lead to reduced healthcare costs and
decreased number of people exposed to harmful radiation. The increased use of GPs giving patients with acute
low-back pain advice to stay active should result in improved healthcare outcomes. Methods development have
contributed to our understanding of translation of research into practice.
Name of contact:
Professor Sally Green
Email/Phone no. of contact:
sally.green@med.monash.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 334076
CIA Name: A/Pr Cynthia Whitchurch
Admin Inst: Monash University
Main RFCD: Medical Bacteriology
Total funding: $346,250
Start Year: 2005
End Year: 2007
Grant Type: NHMRC Project Grants
Title of research award:
Analysis of a chemosensory complex that controls twitching motility and virulence in Pseudomonas
aeruginosaAnalysis of a chemosensory complex that controls twitching motility and virulence in Pseudomonas
aeruginosa
Lay Description (from application):
Pseudomonas aeruginosa is a common bacterium which causes serious life-threatening infections of individuals
with cystic fibrosis, AIDS or who have suffered severe burns or are undergoing cancer chemotherapy.
Infection by this pathogen requires the controlled expression of a large number of virulence factors including
extracellular enzyme, toxins and structures for the attachment and colonisation of host tissues. We have
identified a complex multicomponent regulatory system which coordinates the expression of many of the
virulence determinants of this pathogen. This project aims to dissect the intermolecular interactions and
signalling events which input into, occur within, and output from this regulatory system. This knowledge will
provide a platform for developing rational strategies for the production of new antimicrobials for fighting
infections by this and related pathogens.
Research achievements (from final report):
We have mde signficant progress toward deciphering how Pseudomonas aeruignosa responds to extracellular
cues to control colonisation and virulence factor production
Expected future outcomes:
We expect to identify and characterise protein-protein interactions of Chp chemonsensory sytem of
Pseudomonas aeruginosa and to determine how this system controls twitching motility, extracellular DNA
production and virulence factor production in response to environemetal cues
Name of contact:
Cynthia Whitchurch
Email/Phone no. of contact:
Cynthia.Whitchurch@uts.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 380832
CIA Name: Prof Claude Bernard
Admin Inst: Monash University
Main RFCD: Cell Neurochemistry
Total funding: $325,911
Start Year: 2007
End Year: 2009
Grant Type: NHMRC Project Grants
Title of research award:
Targetting Nogo A as a means to promote CNS axonal regrowthTargetting Nogo A as a means to promote
CNS axonal regrowth
Lay Description (from application):
Unlike the peripheral nervous system, regenerative nerve fiber growth and structural plasticity are limited in
the adult mammalian central nervous system (CNS), following injury. Although lesioned axons can sprout
spontaneously, this regeneration attempt is transitory and no significant re-growth occurs over long distances.
Consequently, injury to the CNS often leads to permanent disability. In many cases, it has been shown that it is
not the absence of growth-promoting molecules in the CNS but rather the presence of axon outgrowth
inhibitors, including components of both CNS myelin and astroglial scars that limit regeneration. Given that
axonal injury is an important pathological determinant of permanent disability in multiple sclerosis (MS), we
have recently investigated the role of the CNS neurite outgrowth inhibitor, Nogo A in the development of a
chronic form of murine MS-like disease. We showed that targeting Nogo A by active and passive
immunization blunts clinical signs, demyelination and axonal damage associated with this model of MS. These
results identify Nogo A as an important determinant of the development of autoimmune-mediated
demyelination and suggest that its blockage may help to maintain and/or to restore the neuronal integrity of the
CNS after autoimmune insult in disease such as MS. The principal goal of this application is to study the
mechanism by which blockade of Nogo A improves clinical outcome in disease like MS and to determine
whether neurite sprouting accounts for such an improvement. Targeting Nogo A and/or its receptor, has the
potential to not only regulate/modulate the process of autoimmune mediated demyelination but could lead to
the first therapy ever offered to patients that helps damaged nerves regenerate after axonal injury following
neurodegeneration due to insult or disease.
Research achievements (from final report):
The motor deficit that characterized multiple sclerosis (MS) patients results from the degeneration and loss of
both large and small caliber axons. The molecular mechanisms that underlie axonal degeneration are relatively
unexplored in both MS as well as its animal model, experimental autoimmune encephalomyelitis (EAE). We
have shown that the axonal growth inhibitor, Nogo-A, plays a central role in the pathophysiology of EAE. A
downstream effector of axonally-dependent Nogo-A-receptor signaling, is Rho-kinase (ROCKII). ROCKII is
known to phosphorylate and thereby inactivate CRMP-2, a critical determinant of tubulin assembly and axonal
growth. Therefore, we examined the protein levels of ROCKII-phosphorylated CRMP-2 (pThr555-CRMP-2) in
the spinal cord of C57BL/6 mice during the course of MOG35-55-induced EAE. Levels of axon-specific
pThr555-CRMP-2 were increased at the onset and peak stages of EAE-disease. This increase directly
correlated with a decrease in the levels of CRMP-2-bound tubulin. Furthermore, we found increased
immunoreactivity to pThr555-CRMP-2 in degenerating axons at and near the site of EAE lesions. This suggest
that phosphorylation of CRMP-2 at the Thr555 site inhibits the normal physiological function of CRMP-2 in
spinal cord axons and is associated with axonal degeneration. Further clinical observation of Nogo Receptor 1
knock-out (ngr1-/-) mice revealed a significant delay in EAE onset when compared with wild-type littermate
controls. Extensive immune-phenotypic analysis revealed no immunological defect in ngr1-/- mice. While
there was an increase in total levels of CRMP-2 in ngr1-/- mice, the levels of pThr555-CRMP-2 was twelvefold lower when compared with MOG35-55-EAE-induced wild-type littermates at peak stage of disease.
Expected future outcomes:
Demyelination is a major event in neurodegenerative disorders. Given that ROCKII mediated phosphorylation
of CRMP-2 downstream of Nogo receptor activation may play a role in the potentiation of axonal degeneration
in EAE. , Therefore the Nogo signal transduction pathway may be a promising target for promoting repair of
axons in neurodegenerative diseases, such as spinal injury, trauma and MS.
NHMRC Research Achievements - SUMMARY
Name of contact:
Bernard
Email/Phone no. of contact:
claude.bernard@med.monash.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 384103
Start Year: 2006
CIA Name: Dr Lesley Day
End Year: 2008
Admin Inst: Monash University
Grant Type: NHMRC Project Grants
Main RFCD: Public Health and Health Services not elsewhere classified
Total funding: $1,157,574
Title of research award:
Tai Chi for independent living: RCT of efficacy of Tai Chi in delaying disability among older people.Tai Chi
for independent living: RCT of efficacy of Tai Chi in delaying disability among older people.
Lay Description (from application):
This study addresses the issue of disability among our ageing population. Preservation of function among our
older citizens, and their capacity to live independently, is of significant social, public health and economic
benefit. The aims of this study are to (1) test the efficacy of Tai Chi in delaying disability among older people,
prior to its onset, (2) investigate the mechanisms by which Tai Chi intervenes in the disability pathway, (3)
determine the cost-benefits of Tai Chi for older people. The study will recruit 670 people over 70 years of age
and randomly assign them to receive either Tai Chi, or a stretching and relaxation program, for a period of 48
weeks. The groups will then be compared to determine if there is any difference in the development of
disability as well as a range of functional outcomes such as strength, balance, depression, arthritic symptoms,
life satisfaction, and falls. This will be the first study world-wide to test the impact of any exercise program
on delaying the manifestation of disability among older people. Robust evidence that Tai Chi can in fact delay
disability will have immediate and significant implications for the maintenance of independence among older
people at a critical time for our ageing population. Translation of these research results to practice will decrease
demand for support services for community dwelling older people, and for places in supported accommodation
facilities. Older people will have improved quality of life, and government and non-government agencies will
experience reduced demand for limited resources. This internationally significant study will also contribute to
understanding the mechanisms by which disability develops, and create the valuable opportunity for continuing
research on attrition of effect and long term adherence to exercise programs.
Research achievements (from final report):
This was the first study world wide to attempt to test the impact of any exericse program on delaying the
manifestation of disability among older people. A total of 503 older people, in the very early stage of disability,
were recruited and received one of two different exercise programs for a 48 week period. Disability outcomes,
and a number of explanatory factors, were monitored. Preliminary results following an interim analysis after 24
weeks of exericse, suggest that the initial promise of the program may not be realised. However, data on the
impact of the full exericse program has not yet been analysed. There may be important messages regarding the
participation of older people in exercise programs.
Expected future outcomes:
Future analysis will test whether the full 48 week exericse program has an impact on delaying disability onset,
and on improving a number of health related outcomes.
Name of contact:
Lesley Day
Email/Phone no. of contact:
lesley.day@muarc.monash.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 384366
Start Year: 2006
CIA Name: Dr Peter Kent
End Year: 2008
Admin Inst: Monash University
Grant Type: Early Career Fellowships (Australia)
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $120,510
Title of research award:
A prospective cohort study of recent-onset low back pain in primary care.A prospective cohort study of recentonset low back pain in primary care.
Lay Description (from application):
Not Available
Research achievements (from final report):
, This Fellowship funding was for an Australian researcher's participation in a large multi-national study of
people seeking care for low back pain, organised by a UK-based research group. The aim of that study was to
identify whether clinically important subgroups of low back pain exist with previously unrecognised treatment
needs. That UK-based study did not proceed., As the aim of that study was still scientifically sound, the study
protocol was redesigned in Australia to include fewer countries and a more practical method. Developing a
more practical method required: reviewing the literature for evidence-based predictors of the outcomes of care;
identifying best-practice statistical method for analysing subgroups and creating a new conceptual framework
for that method; and developing more efficient questions to gather information from patients., New research
collaborations were established with research groups in Denmark and USA. Funding applications for the
Australian and Danish components of the project were submitted. The Danish component was successfully
funded as the main development site. Mid-way through the 4-year Fellowship, the project migrated to Denmark
and the Fellowship ceased. , Since the Fellowship ceased, the Danish collaborators have applied innovative
information technology to the project to allow multilingual, resource-efficient collection of information from
patients. The first 1,500 people entered the study during 2009 and another 5,000 are likely to during 2010.,
Expected future outcomes:
This ambitious project is likely to identify modifiable risk factors for poor outcome from low back pain, and
the way those factors interact. It is also likely to provide a rich source of testable hypotheses about what
treatment particular groups of people respond to and do not respond to.
Name of contact:
Peter Kent
Email/Phone no. of contact:
peter.kent@slb.regionsyddanmark.dk
NHMRC Research Achievements - SUMMARY
Grant ID: 400937
CIA Name: Prof Caroline Finch
Admin Inst: Monash University
Main RFCD: Epidemiology
Total funding: $1,160,492
Start Year: 2006
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
A randomised controlled trial of exercise programs for preventing knee injuriesA randomised controlled trial of
exercise programs for preventing knee injuries
Lay Description (from application):
The promotion of physical activity, either through organised sport or active recreation, is a key public health
strategy in this country. However, there is a risk of injury during this participation and efforts need to be
undertaken to reduce this risk so that spor is safe for all. Sports injury prevention efforts to date in Australia
have been severely hampered by a lack of evidence supporting currently advocated countermeasures. This
concern has been recognised by both the NHMRC and the Commonwealth Department of Health and Ageing.
It is imperative that we formally evaluate the effectiveness of sports injury countermeasures in the context of
broad community level participation in sport, in contrast to previous research focussed on professional sport,
and begin to deliver the preventive measures to the community. Australian football is a popular sport
throughout Australia and it is associated with more medically-treated injuries than any other sport. Knee
injuries are particularly common and can have severe consequences. One of the most commonly recommended
knee injury prevention strategies is a well-designed exercise training program. Despite their potential to
significantly reduce injury rates, the effectiveness of exercise training programs to prevent knee injuries in
football, and indeed in most other sports, has not previously been assessed but has been identified as a priority
research area by the NHMRC. This project will determine the effectiveness of exercise training programs for
preventing knee injuries in community-level football players by monitoring injury rates, player behaviours and
player attitudes before and after the training programs are implemented.
Research achievements (from final report):
Because of the large amount of running and other game-specific manoeuvres necessary to play football,
footballers can sustain injuries to their lower limbs. Lower limb injuries are the most common football-related
injury and can have significant impact for players in terms of need for treatment and being unable to play the
game for a time. While it is well known from laboratory-based studies that strengthening and conditioning the
muscles and control of ligaments around the knee could potentially prevent these injuries, this evidence has not
previously been applied directly to community football. This study developed the first exercise training
program specifically for community footballers to reduce their risks of lower limb injury. The program was
delivered and trailed in two large football leagues in Victoria and Western Australia. The research team worked
with community football coaches and their training support staff to encourage players to undertake the guided
exercise program. The project has led to the refining of an "ideal" exercise training program that other coaches
could implement with their players to prevent lower limb injuries in the future. If players start, in their
preseason, to prepare for their football season using this training program, they are likely to have a reduced risk
of injury and will be able to play fully over the following playing season, with good performance and fitness
benefits.
Expected future outcomes:
Our improved understanding of what motivates coaches to deliver, and players to adopt, exercise training
programs means that we can now deliver a program which is more likely to be successful in the future because
it is highly relevant for, and acceptable to, the culture of community football.
Name of contact:
Caroline Finch
Email/Phone no. of contact:
caroline.finch@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 436620
CIA Name: Dr James BOURNE
Admin Inst: Monash University
Main RFCD: Sensory Systems
Total funding: $460,947
Start Year: 2007
End Year: 2009
Grant Type: NHMRC Project Grants
Title of research award:
Development and maturation of the visual cortexDevelopment and maturation of the visual cortex
Lay Description (from application):
Much of the human brain is devoted to vision, which requires the integrated activity of many interconnected
areas of the cerebral cortex. Damage to these areas is a relatively common complication of preterm delivery
and- or perinatal conditions including trauma and infection. The severity of both the short- and long-term
effects of these lesions appears to be related to the time of the damage. The aim of this project is to investigate
the way in which the multiple visual areas of the brain develop and become 'wired' together in the period
following birth. We will also determine if there are mechanisms which allow alternate routes to be found for
processing visual information while the brain is still establishing connections between its multiple areas. This
will allow us to understand the anatomical and physiological bases of the deficits caused by early damage to
the visual areas of the brain, and perhaps point to strategies that will lead to improved recovery of visual
function.
Research achievements (from final report):
Much of the human brain is devoted to vision, which requires the integrated activity of many interconnected
areas in the neocortex. Damage to these areas is a relatively common complication of preterm delivery and/or
perinatal conditions including trauma and infection. The severity of both short- and long-term effects of these
lesions appears to be related to the time of the damage. This project has demonstrated the ways in which the
visual cortical areas develop in sequence and how they purposefully interact following birth. Furthermore, at
the micro level it has enabled us to define the cellular networks that are involved in plasticity. The outcomes of
this research allow us to understand the anatomical and physiolgical bases of the deficits caused by damage to
the visual cortical areas of the brain early in life. The potential benefits are the development of strategties that
afford improved recovery of visual function.
Expected future outcomes:
The corollary of the outcomes achieved in this present study have been the design of potential strategies using
specific molecules that can afford rewiring of connections.
Name of contact:
Dr James Bourne
Email/Phone no. of contact:
james.bourne@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 436629
CIA Name: Prof David Cooper
Admin Inst: Monash University
Main RFCD: Intensive Care
Total funding: $360,313
Start Year: 2007
End Year: 2011
Grant Type: Established Career Fellowships
Title of research award:
Practitioner FellowshipPractitioner Fellowship
Lay Description (from application):
I am an intensive care physician, clinician and researcher, interested in studying new therapies to improve
outcomes in patienst with acute trauma, sepsis and lung injury. A main focus is independent phase 111 clinical
trials in critically ill patients
Research achievements (from final report):
In 2011, I published two pivotal clinical trials in NEJM, one as first author. I had 70 papers in the past 5 years,
and 23 in 2011. My h-index is 25. Both trials published in NEJM in 2011 (DECRA and PROTECT) have
impacted clinical practice (Marion D. Lancet Neurol. 2011 Jun;10(6):497-8). The publication of the DECRA
trial (N Engl J Med. 2011 April; 364(16): 1493-502) was described as a "fundamental event in the history of
decompressive craniectomy for traumatic brain injury" (Hutchison P, B J Neurosurg 2011; 25(3): 441-442),
and as "one of the most important clinical trials of a novel therapy for severe TBI, and a class 1 study which
should be considered as foundation for an evidence based guideline" (Lancet Neurol. 2011 Jun;10(6):497-8).
DECRA was the first randomised controlled trial of any neurosurgical technique in neurotrauma. It will change
clinical practice and is likely to save Australian health care 1-200 million dollars annually.
Expected future outcomes:
I will lead 2 main research programs: Improving outcomes after traumatic brain injury; and Optimising patient
blood management in critical care. Three NHMRC currently funded multicentre clinical trials (two as CIA) and
the CRE grant (CIA) provide the major components and main funding support for these programs. Organising
an international conference in Italy on clinical trials in intensive care.
Name of contact:
D J (Jamie) Cooper
Email/Phone no. of contact:
jamie.cooper@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 436659
Start Year: 2007
CIA Name: Dr Ian Smyth
End Year: 2009
Admin Inst: Monash University
Grant Type: NHMRC Project Grants
Main RFCD: Genetic Development (incl. Sex Determination)
Total funding: $475,517
Title of research award:
The role of the Frem proteins in development and diseaseThe role of the Frem proteins in development and
disease
Lay Description (from application):
Rare genetics diseases can often provide us with insights into some of the fundamental mechanisms which
control how we develop and live healthy lives. We have identified a family of genes called the Fras and Frem
genes and some of these are mutated in a disorder called Fraser Syndrome. Fraser Syndrome patients have
profound defects in the normal development of their skin and kidneys. We are studying the function of these
genes with a view to understanding not just how Fraser Syndrome develops, but how our organs develop
normally. The genes involved in FS contribute to the "extracellular matrix" which is effectively the scaffolding
which our cells use when developing into our organs. The extracellular matrix is also important in maintaining
our adult tissues and responding to damage. It can act as a physical support and as a key controller of how ours
cells react to growth factors and to each other. This proposal will explore how the Fras and Frem genes
mediate these interactions to control normal development and also to determine how their mutation gives rise
to disease. In doing so we hope to gain insights into more common diseases which affect both the kidney and
the skin.
Research achievements (from final report):
During the course of this project we have furthered our understanding of the role of the Fras and Frem genes in
development. Specifically we have detailed gene expression in a number of developmental animal systems
uncovering gene expression interactions with relevance to human disease caused by mutations in these genes.
We have developed a novel imaging technology to explore developmental defects in these genes and have
applied this to the analysis of a number of different organ systems. We have shown that the Fras and Frem
genes can control Pdgf signalling and the implications of this finding to the study of tissue inflammation are
ongoing. Wehave also shown that mutations in these genes contribute to defects in craniofacial development
including orofacial clefting and craniosynostosis.
Expected future outcomes:
Better understanding of disease features associated with the Fras and Frem genes and the application of
imaging modalities based around Optical Projection Tomogrpahy to better understand features of
developmental disease in model organisms
Name of contact:
Ian Smyth
Email/Phone no. of contact:
ian.smyth@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 436767
Start Year: 2007
CIA Name: Prof Sally Green
End Year: 2009
Admin Inst: Monash University
Grant Type: NHMRC Project Grants
Main RFCD: Therapies and Therapeutic Technology
Total funding: $682,134
Title of research award:
Improving the care for people with acute low back pain by allied health professionals: cluster RCT.Improving
the care for people with acute low back pain by allied health professionals: cluster RCT.
Lay Description (from application):
The project focuses on the NHMRC Clinical Practice Guidelines (CPG) for the management of acute low back
pain, and more specifically the key messages of non-referral to x-ray and advising patients to stay active. A
mixed design approach will be used in line with the framework for evaluating complex interventions (MRC
2000). A qualitative approach using semi-structured interviews with physiotherapists, chiropractors and the
patients of both will be conducted to identify the barriers and enablers to implementation of the evidence-based
clinical practice guideline. The interviews will be underpinned by a theoretical framework grounded in
behavioural theory. Information from the interviews will be used to develop a survey to canvas views of a
larger population of chiropractors and physiotherapists. The results of the interviews and survey will inform the
development of a targeted implementation strategy suitable for use in private physiotherapy and chiropractic
clinics. Potential interventions include educational strategies, patient and practitioner information via various
media, reminder systems and peer leadership.
Research achievements (from final report):
This project evaluated an intervention designed to assist allied health practitioners (physiotherapists and
chiropractors) better manage people with acute low-back pain. This research has led to further articulation of
the complexities of research that aims to improve clinical practice in line with research evidence, and thus has
furthered understanding in the field of implementation science. This project has also extended the methodology
of desinging theory-based behaviour change interventions and the assessment of intervention fidelity. The
project has strengthened partnerships between the Australian-based project team and international leaders in
implementation research.
Expected future outcomes:
Allied health professionals ordering fewer plain x-rays for patients with acute low-back pain can lead to
reduced health care costs and decreased number of people exposed to harmful radiation. The increased use of
health professionals advising patients with acute low-back pain to stay active in line with evidence from
research should result in improved health care outcomes.
Name of contact:
Professor Sally Green
Email/Phone no. of contact:
sally.green@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 436815
Start Year: 2007
CIA Name: A/Pr Cristina Morganti-Kossmann
End Year: 2009
Admin Inst: Monash University
Grant Type: NHMRC Project Grants
Main RFCD: Neurosciences not elsewhere classified
Total funding: $397,535
Title of research award:
Role of post-traumatic hypoxia in the exacerbation of cerebral inflammatory response elicited by brain
injuryRole of post-traumatic hypoxia in the exacerbation of cerebral inflammatory response elicited by brain
injury
Lay Description (from application):
Traumatic brain injury is the major cause of death in the young population below the age of 40 years.
Approximately 25% of patients that survive head injury remain with permanent neurological disabilities with
considerable family, professional and economic costs. Extensive research has shown that not all brain damage
occurs at the time of injury, but rather evolves over the hours and days following trauma. Secondary injury may
result from various factors including hypoxia (insufficient oxygen) as a consequence of respiratory distress that
occurs in about 50% of patients with severe head trauma. Hypoxia is known to significantly worsen the
neurological impairment and potentially lead to death. Brain injury and hypoxia have the ability to separately
trigger cerebral inflammation. A dual role has been attributed to inflammation: to promote tissue repair but also
add further damage through the release of neurotoxic substances. We hypothesise that hypoxia occurring after
traumatic brain injury enhances the inflammatory response in the brain and aggravate tissue damage as well as
neurological dysfunction. This hypothesis will be tested on a rat model of brain injury whereby the animals will
be exposed to moderate-severe hypoxia immediately after trauma. The production of multiple inflammatory
mediators will be quantified in the brain tissue and also in cerebrospinal fluid. The concentration of these
mediators will be compared with the levels of cellular injury proteins known to increase following injury to
determine whether a correlation exists. In a clinical study on patients, we will measure the same inflammatory
mediators and proteins in the cerebrospinal fluid and blood of individuals with severe head injury. The
suitability of these factors for potential use as diagnostic/prognostic markers of either hypoxia or injury will be
determined.
Research achievements (from final report):
Epidemiological data have shown that a hypoxic event following head injury is associated with mortality and
disability in humans. However, the mechanisms exacerbating brain damage and neurological function after
brain trauma remain obscure. In this study we demonstrated that a hypoxic event following traumatic brain
injury (TBI) in a rat model of diffuse brain damage worsens neurological deficit and exacerbates
neuroinflammation by means of brain infiltration of blood macrophages, accumulation of microglia and glial
activation. The synthesis of the cytokines TNF, IL-1 and IL-6 was more elevated in the cortex of TBI-hypoxic
rats than animals with TBI or hypoxia alone. Most importantly, in this model of diffuse TBI, hypoxia enhanced
axonal pathology in the corpus callosum and brain stem up to 2 weeks post-injury. , In the clinical study based
on patients (up to 36) with severe head injury, the occurrence of hypoxia immediately after the accident
showed a trend towards a protracted increase in the concentration of cytokines TNF, IL-2, IFN, GM-CSF in the
cerebrospinal fluid over 6 days as compared to patients with TBI without hypoxia. In addition, when surrogate
markers of brain damage were quantified in the blood of these patients, S-100 and myelin basic protein were
found more elevated in TBI-hypoxic group as compared to TBI normoxic individuals, whereas the biomarker
neuronal specific enolase was not different between the groups., Collectively these studies corroborate in two
distinct systems the detrimental effects of post-TBI hypoxia mostly with enhanced brain inflammation. The use
of the standardised animal model allowed us to deepen our understanding of the role of hypoxia on
neurological deficit, tissue damage and neuroinflammation at cellular and humoral level. The identification of
injury markers reflecting exacerbated brain damage may have significant applications in the clinic.
Expected future outcomes:
This study has spurred further investigations in patients and rat model of TBI on the activation of the
kynurenine pathway which metabolises tryptophan, producing quinolinic acid, a potent neurotoxin.
NHMRC Research Achievements - SUMMARY
Electrophysiological and therapeutic studies on the animal model will elucidate functional changes leading to
neurological impairment and strategies to improve outcomes after TBI-hypoxia.
Name of contact:
Cristina Morganti-Kossmann
Email/Phone no. of contact:
cristina.morganti-kossmann@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 456097
Start Year: 2007
CIA Name: Dr Terrence Haines
End Year: 2009
Admin Inst: Monash University
Grant Type: NHMRC Project Grants
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $524,137
Title of research award:
Randomised controlled trial of multimedia patient education approaches to preventing in-hospital
fallsRandomised controlled trial of multimedia patient education approaches to preventing in-hospital falls
Lay Description (from application):
In hospital falls are one of the most frequently occurring adverse events in Australian hospitals. They are the
cause of considerable patient morbidity, stress to family members and care givers, and health care resource use.
However, there are many potential causes of in-hospital falls which has made minimising them a difficult task
for hospitals around the country. Recent evidence has indicated that a patient intervention strategy is useful for
preventing in-hospital falls as a part of a multi-factorial falls prevention program. This research aims to
investigate the effectiveness and economic benefit of two approaches to providing patient education for the
prevention of in-hospital falls. Patients at high risk for falls will be recruited from the Princess Alexandra
Hospital and be randomly allocated to either a DVD + 4 sessions of face-to-face education with an
occupational therapist program, to a DVD alone education program, or to a usual care with no additional
education control condition. Patients will be followed up until their discharge from hospital and the number of
in-hospital falls they incur will be compared between groups. It is expected that both the DVD + 4 sessions of
face-to-face education with an occupational therapist program, to a DVD alone education program will be
effective in reducing falls and that the DVD alone education program will demonstrate the greater costeffectiveness in reducing falls. Stemming from this research, it is anticipated that a cost-effective resource for
preventing in-hospital falls will be developed and evaluated such that it can be used in hospitals Australia wide.
Research achievements (from final report):
The patient education program developed as a part of this research reduced falls amongst cognitively intact
hospital inpatients by 50% across acute and subacute hospital wards. This is the first time a single intervention
has been shown to reduce falls in a hospital population internationally. This program has been the subject of
keynote addresses at national and international conferences and has now been translated into practice in several
hospitals around Australia, Hong Kong and the United Kingdom. , This project advanced the methodology of
conducting falls research in hospitals by demonstrating that hospital incident reporting systems under-report
falls by ~30%, creating a considerable source of bias in some studies. , This study advanced the methodology
of conducting meta-analyses in fields where the outcome of interest is a recurrent event by demonstrating that
standard meta-analysis approaches create confidence intervals that are too narrow. , This study demonstrated
that hospital patients face a high burden of falls once they have been discharged from hospital, but have little
idea of effective intervention strategies, so are unable to effectively self-manage.
Expected future outcomes:
Further work build on this study is currently underway to better understand risk taking by older adults, to
examine the economic efficiency of hospital falls prevention programs and to develop programs to prevent falls
once older adults are discharged from hospital.
Name of contact:
Terry Haines
Email/Phone no. of contact:
terrence.haines@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 457088
CIA Name: Prof Mark Stevenson
Admin Inst: Monash University
Main RFCD: Epidemiology
Total funding: $812,867
Start Year: 2007
End Year: 2013
Grant Type: NHMRC Research Fellowships
Title of research award:
Uncoupled Research FellowshipUncoupled Research Fellowship
Lay Description (from application):
I am a epidemiologist with a research focus on road and child injury. This includes expertise in both clinical
and observational research related to injury
Research achievements (from final report):
Over the course of the Fellowship I completed a suite of observational studies that contributed directly to
policy and practice. From my cohort study on mild traumatic brain injury among non-elite rugby players which
highlighted that current management practices are insufficient to manage this burgeoning problem, through to
findings from the Heavy Vehicle Crash Study - a population-based case-control study which contributed to the
development of the safe-rates legislation which was recently introduced by the Federal Government.
Expected future outcomes:
Since the Fellowship supported me whilst undertaking 4 significant population-based studies and in which 2 of
these studies I am still analysing data, I anticipate there will continue to be considerable publications and
dissemination of the findngs over the next 12-18 months.
Name of contact:
Mark Stevenson
Email/Phone no. of contact:
Mark.Stevenson@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 465103
CIA Name: A/Pr Belinda Gabbe
Admin Inst: Monash University
Main RFCD: Epidemiology
Total funding: $471,059
Start Year: 2007
End Year: 2011
Grant Type: Career Development Fellowships
Title of research award:
Improving the measurement and monitoring of long term outcomes following trauma.Improving the
measurement and monitoring of long term outcomes following trauma.
Lay Description (from application):
Not Available
Research achievements (from final report):
Traumatic injury remains a leading cause of the global burden of disease and is one of the seven National
Health Priority Areas. Advancements in the treatment of injuries has led to a global reduction in injury-related
death increasing the importance of measuring the burden of non-fatal injury, including the degree of functional
loss, ongoing disability and lost quality of life experienced by survivors. The key focus of the research
undertaken during this Career Development Award was the development, validation, and implementation of a
methodology for capturing long term disability outcomes following injury via trauma registries, one of the
most detailed source of injury-specific data available globally. Uptake of this methodology by the Victorian
State Trauma Registry and Victorian Orthopaedic Trauma Outcomes Registry has resulted in the largest
repository of long term injury disability outcomes and the only injury-specific monitoring systems to routinely
collect data on long term outcomes other than mortality. Additional observational and qualitative studies
undertaken during this Award have focused on the individual and societal impacts of injury, experiences with
the delivery of trauma care, and comparing outcomes of different treatment approaches and systems of care.
The research has resulted in an improved understanding of the course of recovery of following serious injury,
factors contributing to good and poor outcomes, and the impact of specialised trauma centre care on the quality
of survival of injured patients.
Expected future outcomes:
This research will allow population-based monitoring of the long term outcomes following injury, including
the capacity to measure the impact of changes in delivery of care on patient outcomes. The data collected will
also provide contribute to validation and improvement of measurement of the global burden of non-fatal injury.
Name of contact:
Belinda Gabbe
Email/Phone no. of contact:
belinda.gabbe@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 465142
CIA Name: Dr Yuanyuan Wang
Admin Inst: Monash University
Main RFCD: Rheumatology and Arthritis
Total funding: $282,008
Start Year: 2007
End Year: 2010
Grant Type: Early Career Fellowships (Australia)
Title of research award:
The effect of sociodemographic and lifestyle factors on the risk of primary and revision joint replacement.The
effect of sociodemographic and lifestyle factors on the risk of primary and revision joint replacement.
Lay Description (from application):
Not Available
Research achievements (from final report):
The project explored the ethnic disparity in total joint replacement utilization in Australia, and examined
associations between lifestyle factors including obesity, physical activity, and diet, and the risk of total joint
replacement for osteoarthritis. The research on the disparities of joint replacement utilization is crucial to
healthy policy in terms of the issue of equity: health service and resources should be fairly distributed on
clinical needs, but not by patient's cultural or socioeconomic background. The findings of the research identify
the potentially modifiable risk factors for osteoarthritis, contribute better understanding of the pathogenesis of
osteoarthritis, and inform novel preventive strategies for osteoarthritis. For example, muscle mass was shown
to be beneficial to knee cartilage, and fat mass to be detrimental to knee cartilage and associated with an
increased risk of total joint replacement. It may be that for effective prevention of osteoarthritis, weight loss
programs should focus on both fat mass reduction and muscle maintenence: simple weight loss alone may be
insufficient. Thus, these may facilitate more effective strategies to prevent osteoarthritis in the future.
Expected future outcomes:
Patient-related factors associated with the risk of revision joint replacement and the effect of adult weight gain
on the risk of total joint replacement will be further explored. Extension of this work may provide a stronger
basis to enable intervention studies to be conducted to reduce the risk of osteoarthritis.
Name of contact:
Yuanyuan Wang
Email/Phone no. of contact:
Yuanyuan.Wang@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 490992
Start Year: 2009
CIA Name: Prof Michael Lenne
End Year: 2012
Admin Inst: Monash University
Grant Type: International Collaborations
Main RFCD: Public Health and Health Services not elsewhere classified
Total funding: $178,706
Title of research award:
WHEELER BEHAVIOUR AND SAFETY (2-BE-SAFE)WHEELER BEHAVIOUR AND SAFETY (2-BESAFE)
Lay Description (from application):
The aim of this project is to design and implement a broad-ranging research program that produces in-depth
knowledge of motorcycle rider behaviour, performance, and safety that can be used to inform and develop a
broad, and integrated package of countermeasures and-or public policies to improve the safety of motorcycle
riders. A key focus of the research program will be on the identification and characterisation of errors that give
rise to incidents and crashes involving motorcycle riders. Australian motorcycle riders are three times more
likely to be involved in a casualty crash than car drivers, and comprised 14% of the national road toll in 2005.
The proposed research program aims to improve motorcycle safety by developing appropriate countermeasures
that will be derived from the findings of simulator experiments, on-road studies, focus groups, and surveys.
The results of these studies will be used to develop guidelines and recommendations for improving motorcycle
safety.
Research achievements (from final report):
This was the first major project to examine motorcycle safety using human factors approaches. The European
project 2-be-Safe involved 27 instutions working together to develop new methods for studying motorcyclist
safety and to evaluate different approaches that could lead to safety improvements. The development of
research platforms to examine rider behaviour using simulation and naturalistic (on-road) approaches were key
outcomes of the broader program. NHMRC-EU funding supported Australian involvement in this program.In a
large proportion of motorcycle crashes the car driver either fails to see a motorcyclist all together or detects
them too late. In this project Australian researchers worked with the European consortium to better understand
how aspects of rider and motorcycle conspicuity impact how well a driver will detect the rider in traffic.
Expected future outcomes:
It isexpected that these findings will be used by road authorities to inform policies that will improve road user
safety.
Name of contact:
Michael Lenné
Email/Phone no. of contact:
Michael.Lenne@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 491109
CIA Name: A/Pr Velandai Srikanth
Admin Inst: Monash University
Main RFCD: Geriatrics and Gerontology
Total funding: $1,323,362
Start Year: 2008
End Year: 2012
Grant Type: NHMRC Project Grants
Title of research award:
A population-based cohort study of brain ageing - rates of brain structural change, functional effects, and
mechanismsA population-based cohort study of brain ageing - rates of brain structural change, functional
effects, and mechanisms
Lay Description (from application):
This study will provide unique longitudinal Australian data on the effects and causes of brain aging in a
population-based sample of older people. The results may assist in preventing dementia and falls, major public
health problems in older Australians.
Research achievements (from final report):
TASCOG is a cohort study of 430 older people randomly selected from the population followed up twice after
baseline assessment, over a period of 5 years. The principal aims are as follows:In a randomly selected
population-based cohort of people aged over 60 years (n = 400) followed over 5 years, we aim to study
cerebrovascular mechanisms involved in brain ageing:1.The rates of change in key age-related brain structural
volumes [white matter hyperintensity volume (WMHV), brain parenchymal volume (BPV) and hippocampal
volume (HV)].2.The impact of changes in brain structural volumes on change in cognition, gait, and the risk of
incident falls.3.The relationship between physical activity, endothelial function and change in brain structural
volumes over time.4.The effects of novel and potentially harmful (advanced glycation endproducts, AGEs) or
potentially protective (soluble receptor for advanced glycation endproducts - sRAGE) biochemical factors on
change in brain structural volumes over time. Data collection was completed in late 2012. Overall, we have
followed up 346 people in phase 2 and 279 in phase 3. Data cleaning and MRI processing for phase 3 has
required more intensive input and was completed omplete by mid-2013. Data from the first 2 phases are being
analysed from several perspectives. the first of these papers has been accepted by the Journal of the American
Geriatrics Society. Several further manuscript are in submission on the association of white matter lesion
progression and risk of incident falls, the trajectory and predictors of decline in cognitive function and quality
of life, and the effect of lifestyle (physical activity on brain changes). These data have already been presented
at major international meetings as well as being submitted for others. In addition, these longitudinal data now
are an integral component of genome wide meta-analysis looking at novel gene variants contributing to brain
ageing - as part of the CHARGE consortium.
Expected future outcomes:
This project has provided vast dataset with rich biological measures - it will provide novel data that will reach
publication on several fronts over the next 2 years
Name of contact:
Velandai Srikanth
Email/Phone no. of contact:
velandai.srikanth@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 509349
CIA Name: Prof Russell Gruen
Admin Inst: Monash University
Main RFCD: Surgery
Total funding: $314,312
Start Year: 2008
End Year: 2011
Grant Type: Career Development Fellowships
Title of research award:
Refining methods for obtaining, synthesising and interpreting research evidence in surgeryRefining methods
for obtaining, synthesising and interpreting research evidence in surgery
Lay Description (from application):
Research evidence plays a crucial role in improving clinical care. However the main forms of evidence and the
tools that facilitate evidence use - namely randomised controlled trials (RCT) & structured systematic reviews
of existing research - have had limited application in surgery for a variety of reasons. This project aims to
promote the use of research evidence in surgical decision making by developing tools tailored to the
predominance of non-RCTs in surgery & surgeons' information needs.
Research achievements (from final report):
In this 4 year period I have advanced various aspects of science in health services, surgery and trauma care. I
have published major articles on topics ranging from the sustainability of health services, to the early
management of severe injury, and how to measure the performance of trauma care and trauma systems. I have
benefited from good mentorship and support, and have developed an international network of collaborators and
researchers on similar topics, and have attracted significant project and program funding to support this work
into the future. During this period of NHMRC support I became a full professor and head of department.
Expected future outcomes:
I am continuing on with an NHMRC Practitioner Fellowship and will continue to develop a world class
research program and work on using research to improve care of injured people globally.
Name of contact:
Professor Russell Gruen
Email/Phone no. of contact:
r.gruen@alfred.org.au
NHMRC Research Achievements - SUMMARY
Grant ID: 544304
CIA Name: Prof Stephen Jane
Admin Inst: Monash University
Main RFCD: Dermatology
Total funding: $579,138
Start Year: 2009
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
Defects in epidermal morphogenesis in Grainyhead-like gene deficient miceDefects in epidermal
morphogenesis in Grainyhead-like gene deficient mice
Lay Description (from application):
The cells of the skin play an essential role in the development of the mammalian embryo. They are critical for
forming a protective barrier against infection and external toxins, for preventing excess fluid loss, for repair of
defects and wounds , and for the generation of hair. Our laboratory has identified a family of genes that are
critical for these processes. The aim of this study is to determine the relationship between these genes to further
our understanding of the skin and its functions
Research achievements (from final report):
This project examined the role of the Grainy head-like factors in epidermal morphogenesis. We made,
excellent progress in understanding the role of Grhl3 in both embryonic epidermal development and in, adult
epidermal homeostasis. We also made inroads in deciphering interactions between the family, members in
epidermal development.
Expected future outcomes:
These studies pave the way for further developments in understanding and management of disease processes
that involve defective epidermal migration such as failed wound repair and neural tube defects.
Name of contact:
Stephen Jane
Email/Phone no. of contact:
stephen.jane@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 545865
CIA Name: Dr Kathleen Burman
Admin Inst: Monash University
Main RFCD: Motor Control
Total funding: $554,656
Start Year: 2009
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
Plasticity of sensorimotor representations in adult primate cortexPlasticity of sensorimotor representations in
adult primate cortex
Lay Description (from application):
Cells in some regions of the brain, collectively known as the sensorimotor cortex, control our capacity to
purposefully move the arms and hands. Damage to these regions in adults causes severe deficits. However,
rehabilitative training can restore some control over the muscles. To understand how the brain circuits change
to compensate for injury, and what effect rehabilitation may have on these changes, I will study cellular
alterations in the movement control pathways in the cerebral cortex.
Research achievements (from final report):
This project focused on how the non-human primate brain reorganises after injury to the areas responsible for
sensation and movement, including a close examination of the connections of premotor areas. The results have
provided limited support for the idea that focal ischemic lesions followed by spontaneous recovery of arm
movement promote massive rearrangements in cortico-cortical sensorimotor pathways. The tracer experiments
indicate that parietal somatosensory areas 1 and 2 are directly linked to the ventral premotor cortex in both
normal and lesioned animals. However, they suggest differences in the density and distribution of connections
from the granular and retroinsular cortices to the ventral premotor cortices, with lesioned animals showing a
more robust projection. These results suggest that rodent studies alone may not provide the best information for
strategies aimed at improving motor function in humans recovering from stroke. Our results also add to our
understanding of the organisation of motor areas in the non-human primate brain.
Expected future outcomes:
These results enhance our understanding of the finer organisation of motor areas in the non-human primate and
how the brain controls movement and may lead to better strategies for managing stroke recovery in humans.
Name of contact:
Kathleen Burman
Email/Phone no. of contact:
kathleen.burman@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 545925
Start Year: 2009
CIA Name: Prof David Walker
End Year: 2011
Admin Inst: Monash University
Grant Type: NHMRC Project Grants
Main RFCD: Foetal Development and Medicine
Total funding: $579,138
Title of research award:
Cerebrovascular Effects of Intrauterine Hypoxia: Contribution to Perinatal Brain InjuryCerebrovascular Effects
of Intrauterine Hypoxia: Contribution to Perinatal Brain Injury
Lay Description (from application):
During pregnancy, delivery of oxygen and nutrients to the growing fetus is sometimes disturbed, and can lead
to injury of the developing brain. In this project we investigate the idea that low oxygen (hypoxia) causes brain
demage to blood vessels in the fetal brain, and new blood vessesl produced in an attempt to repair this damage
are fragile and prone to rupture, explaining the high incidence of bleeding in the brain of prematurely-born and
full term infants that experience birth hypoxia.
Research achievements (from final report):
We have been successful in showing that a single, brief episode of global hypoxia/asphyxia in the near-term
sheep fetus causes increased expression of Vascular Endothelial Growth Factor (VEGF) in small blood vessels
in many regions of the brain. This is also associated with leakage of plasma proteins into the brain in some
regions, indicative of increased blood vessel permeability, or breakdown of the normally tight junctions of the
blood-brain barrier - this was observed in particularly in periventricular and subcortical white matter, and may
be one of the reasons why these regions are particularly susceptible to hypoxia-induced brain damage. The
single hypoxic episode also produced changes in other proteins associated with the remodelling of blood
vessels, such as angiopoietin-1, and again this was particularly evident in blood vessels passing through white
matter. There were changes in the overall morphology of blood vessels, observed as an increase in the relative
number of large (?100 µm) versus small (?10 µm) blood vessels when measuring the perimeter of small
vessels. These changes were evident at 48 h following hypoxia in white but not grey matter, suggesting that
there was a prolonged loss of the mechanisms that regulate blood vessel size. These findings have significance
for perinatal brain imaging studies which currently are not optimized for the identification of microvascular
damage or changes of perfusion. ?
Expected future outcomes:
Our results will alert clinicians to the need to examine brain blood flow and brain blood vessels closely in
preterm and term neonates who suffer oxygen deprivation at birth. New imaging techniques are required that
identify brain regions with abnormal blood flow, and to determine if small haemorrhages are present.
Name of contact:
David Walker
Email/Phone no. of contact:
david.walker@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 546005
Start Year: 2009
CIA Name: Prof Euan Wallace
End Year: 2011
Admin Inst: Monash University
Grant Type: NHMRC Project Grants
Main RFCD: Foetal Development and Medicine
Total funding: $511,295
Title of research award:
Preventing Prenatal Brain Injury in Fetal Growth RestrictionPreventing Prenatal Brain Injury in Fetal Growth
Restriction
Lay Description (from application):
Intrauterine fetal growth restriction (IUGR) is a serious complication of pregnancy associated with increased
perinatal morbidity and mortality. In particular, IUGR infants have a high risk of perinatal brain injury which
is likely to arise from damage before birth. Our aim is to use an ovine model of IUGR to define the causes of
that brain injury and to develop new therapies that could be offered to women to protect their unborn baby.
Research achievements (from final report):
In this project we demonstrated that impaired fetal growth was associated with injuries to the developing brain
that resulted in disability of the newborn. We went on to show that this brian injury was related to oxidtive
stress in the growth restricted fetus and that treatment of the pregnant mother with melatonin - a powerful
antioxidant - reduced oxidative stress in the developing fetus and prevented brain injury. The melatonin
treatment improved developmental outcome of the newborns. The project was udnertaken using an
experimental sheep model of growth restriction. However, the results show for the first time that it is possible
to treat an unborn baby before it is born and prevent brain injury.
Expected future outcomes:
The results of this project have been used to design a clinical trial where the treatment will be offered to
pregnant women whose baby is severely growth restricted.
Name of contact:
Professor Euan Wallace
Email/Phone no. of contact:
euan.wallace@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 546238
CIA Name: A/Pr James Friend
Admin Inst: Monash University
Main RFCD: Surgery
Total funding: $187,213
Start Year: 2009
End Year: 2009
Grant Type: NHMRC Development Grants
Title of research award:
The NanoNautilus : A Breakthrough in the Successful Treatment of Strokes and Other Cerebrovascular
DiseasesThe NanoNautilus : A Breakthrough in the Successful Treatment of Strokes and Other
Cerebrovascular Diseases
Lay Description (from application):
Strokes are one of the biggest killers of Australians and are becoming increasingly so every year. Bleeding
from the brain involves extremely delicate and dangerous medical treatments. The development of
NanoNautilus [TM]---a remote-controlled steerable microcatheterusing world-first miniaturization technology--will revolutionise current practises and greatly reduce the current risk with medical intervention.
Research achievements (from final report):
Strokes are one of the biggest killers of Australians and are becoming increasingly so every year. Bleeding
from the brain involves extremely delicate and dangerous medical treatments. This project helped develop the
NanoNautilus [R]---a remote-controlled steerable microcatheter using world-first miniaturization technology,
where we developed our triple-axis micromotor and mounting technology to the point where the device can be
taken forward in further animal trials for actual application in navigating the arteries of the brain. Two patent
applications to PCT have resulted from this grant, as have four published journal papers at a minimum. Ex-vivo
and animal trials in pigs are ongoing. Our chief achievement is in creating and validating a novel
microtechnology for navigating the neurovasculature, overcoming significant technical hurdles in achieving
controllable motion of a catheter tip.
Expected future outcomes:
The future of this work is the use of the technology as a complete device in human trials at the Royal
Melbourne Hospital's Neurointervention Centre.
Name of contact:
James Friend
Email/Phone no. of contact:
james.friend@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 606402
CIA Name: Prof Christina Mitchell
Admin Inst: Monash University
Main RFCD: Signal Transduction
Total funding: $689,474
Start Year: 2010
End Year: 2012
Grant Type: NHMRC Project Grants
Title of research award:
Role of the 72kDa 5-phosphatase in human diseasesRole of the 72kDa 5-phosphatase in human diseases
Lay Description (from application):
We have identified a novel gene, Inpp5e, that when mutated causes a disease similar to Joubert syndrome and
MORMS disease which leads to abnormal movements, developmental delays, mental retardation, abnormal
breathing and eye movement. We have identified a candidate gene for these diseases and have shown that
deletion of this gene in mice results in similar pathology. We aim to determine the mechanism by which Inpp5e
regulates human development and disease.
Research achievements (from final report):
We characterised the function of a human gene, Inpp5e, in mice and cultured cells. The INPP5E gene is
mutated in human ciliopathy syndromes, which are disorders characterised by developmental abnormalities
affecting organs including the brain and kidneys. There are currently no cures or successful treatments for
ciliopathy syndromes. How mutation of INPP5E causes developmental abnormalities is unknown and formed
the focus of this research. We generated mice harbouring deletion of the Inpp5e gene and observed
abnormalities which recapitulated the human ciliopathy syndromes. These mice provided valuable tools for
studying the basis of disease in INPP5E mutated ciliopathies. We conducted studies in cells to uncover how
Inpp5e regulated signalling pathways which contribute to human diseases such as polycystic kidneys.
Collectively, these studies revealed novel and signifcant roles for INPP5E, and this research may reveal future
therapeutic strategies for ciliopathies.
Expected future outcomes:
We have generated mice harbouring Inpp5e deletion to understand the basis of disease evident in various
organs arising from Inpp5e mutation/deletion. In ongoing studies, we will uncover the molecular pathways
coordiated by Inpp5e in these tissues and endeavour to define novel therapeutic targets/strategies for ciliopathy
treatment.
Name of contact:
Prof. Christina Mitchell
Email/Phone no. of contact:
christina.mitchell@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 606479
Start Year: 2010
CIA Name: Dr Suzanne Miller
End Year: 2012
Admin Inst: Monash University
Grant Type: NHMRC Project Grants
Main RFCD: Foetal Development and Medicine
Total funding: $589,545
Title of research award:
Treatment of Cerebral Palsy - An Experimental ApproachTreatment of Cerebral Palsy - An Experimental
Approach
Lay Description (from application):
Cerebral palsy is characterised by disordered movement evident early in life leading to lifelong disability. The
motor disorder arises from an abnormality within the white-matter of the brain that is non-progressive and is
identifiable soon after birth. In humans and experimental models of fetal infection there is an increase in
markers of inflammation. We will use induce ovine fetal infection and white matter injury to examine if antiinflammatory treatments can prevent fetal brain damage.
Research achievements (from final report):
Intrauterine infection, such as occurs in chorioamnionitis, is a principal cause of preterm birth and is a strong
risk factor for injury to the developing brain and subsequent short- and long-term neurological morbidities,
including cerebral palsy. The major neuropathology arising from chorioamnionitis and preterm birth is white
matter brain injury, particularly periventricular leukomalacia. White matter brain injury in the preterm brain
most likely arises from damage to the oligodendrocyte lineage of cells, where the role of mature
oligodendrocytes is to myelinate developing axons, so-called white matter development. This project was
undertaken in fetal sheep and proposed that it is possible to prevent fetal white matter brain injury associated
with experimental intrauterine infection. Specifically, we aimed to prevent brain injury by targeting the
injurious pathways initiated by a fetal inflammatory response and upregulation of pro-inflammatory cytokines.
Over the course of this grant we examined and compared the neuroprotective properties of three experimental
therapies - melatonin, sulfasalazine and stem cells derived from placental membranes. We determined that each
of these treatments has anti-inflammatory and/or anti-oxidant properties and may be safe to use in humans with
pregnancy or birth complications. The examination of these treatments in the setting of experimental
chorioamnionitis will lead to further comprehensive assessments to determine the oligodendrocyte cell types
that are protected and anti-inflammatory mechanisms of action. This work has been presented at numerous
national and international meetings and has led to completion of a PhD project.
Expected future outcomes:
This project will lead to multiple (>5) publications over the next 18 months. We expect to be in a position to
apply for further NHMRC funding in 2014 or 2015 to undertake an in-parallel human and experimental trial to
confirm treatment efficacy in infants diagnosed with chorioamnionitis.
Name of contact:
Dr Suzanne Miller
Email/Phone no. of contact:
suzie.miller@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 606544
CIA Name: A/Pr Velandai Srikanth
Admin Inst: Monash University
Main RFCD: Haematological Tumours
Total funding: $394,460
Start Year: 2010
End Year: 2013
Grant Type: Career Development Fellowships
Title of research award:
Cerebrovascular Disease and Dementia in Ageing PopulationsCerebrovascular Disease and Dementia in
Ageing Populations
Lay Description (from application):
Media Summary not available
Research achievements (from final report):
This award has enabled me to be very successful in areas of research in stroke, dementia, gait and falls with an
emphasis on the interface between cerebrovascular disease and dementia. It has led to significant research
translation in the management of transient ischaemic attack (TIA) for which a novel hospital pathway was
developed and evaluated resulting in an effective and cost-saving program. In addition, several cerebrovascular
markers of future risk of falls and gait disability in older people were identified. Finally, a major program of
research examining the relation between type 2 diabetes mellitus and dementia was begun, with some key
findings relating DM to brain atrophy generated. These findings may lead to new ways to treat/prevent
dementia.
Expected future outcomes:
The above research has ste the platform for further innovation particularly in the field of diabetes and dementia
which will be a major focus for the next 5 years.
Name of contact:
Velandai Srikanth
Email/Phone no. of contact:
velandai.srikanth@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 606660
CIA Name: Prof Robert Medcalf
Admin Inst: Monash University
Main RFCD: Central Nervous System
Total funding: $499,322
Start Year: 2010
End Year: 2012
Grant Type: NHMRC Project Grants
Title of research award:
To understand the role of the plasminogen activating and matrix metalloproteinase systems in traumatic brain
injuryTo understand the role of the plasminogen activating and matrix metalloproteinase systems in traumatic
brain injury
Lay Description (from application):
Tissue-type plasminogen activator (t-PA) is known for its role as a clot dissolving protein. It is present in the
brain and following traumatic brain injury (TBI), it can worse brain cell damage. We have established a mouse
model of TBI . We will compare brain damage in mice that are deficient in or have high amounts of t-PA. We
will also determine whether the recovery rate post-TBI can be improved using specific t-PA blockers. This
project may provide new therapies for TBI.
Research achievements (from final report):
The matrix metalloproteinases (MMPs) and the plasminogen activating system both contribute to extracellular
proteolysis in the brain. MMPs degrade the blood-brain barrier (BBB) and cause an increase in oedema. t-PA
can also enhance extravasation of plasma proteins into the brain via interaction and subsequent induction of
MMP-9 expression. We established the controlled cortical impactor (CCI) mouse model of TBI to understand
how t-PA and MMPs exert their detrimental effects after TBI. We showed that mice expressing high
constitutive levels of endogenous tPA in the brain undergo greater BBB damage, have larger lesions and
impaired motor function following TBI. tPA-/- mice were relatively protected from BBB damage after TBI.
We also showed that neuronal over-expression of tPA resulted in recruitment of MMP-9 and MMP-3 at 3h
post-TBI. Rather than free t-PA being responsible for this effect, we then made the surprising discovery that
the formation of complexes between t-PA and its inhibitor PAI-1, was promoting extravasation via signalling
through LDL receptors and increasing MMP-3 activity. Importantly, we showed that blocking of MMP-3
activity reduced TBI severity. We also showed that tPA-PAI-1 complexes were present in the cerebrospinal
fluid (CSF) in the majority of TBI cases, yet was absent in mild TBI cases and non-TBI controls. Surprisingly,
MMP-9 activity was dramatically increased in the vast majority of CSF samples from TBI patients. Hence both
tPA:PAI-1 complex and MMP-9 levels in CSF are correlated with TBI in humans.
Expected future outcomes:
Blockade of tPA-PAI-1 complex formation or downstream signalling via LDL receptors could be a novel
means to improve outcome following TBI. Also, targeting MMP-3 may also be of benefit in this condition.
Name of contact:
Robert Medcalf
Email/Phone no. of contact:
robert.medcalf@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 606732
Start Year: 2010
CIA Name: A/Pr Terrence Haines
End Year: 2013
Admin Inst: Monash University
Grant Type: Career Development Fellowships
Main RFCD: Rehabilitation and Therapy (excl. Physiotherapy)
Total funding: $394,460
Title of research award:
Uptake and economic efficiency of falls prevention intervention: Developing stratergies that will enhance
translationUptake and economic efficiency of falls prevention intervention: Developing stratergies that will
enhance translation
Lay Description (from application):
Media Summary not available
Research achievements (from final report):
I led the development of a patient education program for the prevention of falls in hospitals. This program was
the first single intervention strategy shown to prevent falls amongst older hospital patients. This program has
now been the subject of state-wide roll-out initiatives in Queensland and Western Australia. I led the first
longitudinal survey of participation in falls prevention activities by older, community dwelling Australians
which has identified key factors associated with sustained participation. This information has helped form an
online education short course in exercise prescription for falls prevention which has itself been subject to a
randomised trial compared to a traditional face-to-face education method for delivery of continuing education
for health professionals.
Expected future outcomes:
An evaluation of the Western Australian roll-out of my patient education program has itself been another trial
of this program which will shortly be published. We have ~100 enrollees for the exercise prescription for falls
prevention short course that we are running in July 2014, adding to the 150 we have previously trained.
Name of contact:
????Terry Haines?, T
Email/Phone no. of contact:
Terrence.haines@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 628312
Start Year: 2010
CIA Name: Dr Mary Tolcos
End Year: 2012
Admin Inst: Monash University
Grant Type: NHMRC Project Grants
Main RFCD: Foetal Development and Medicine
Total funding: $668,387
Title of research award:
Does caffeine affect the development of the very immature brain: dose response relationship?Does caffeine
affect the development of the very immature brain: dose response relationship?
Lay Description (from application):
Premature birth is a major health problem worldwide. Preterm babies often develop apnoea of prematurity
(AOP), which is commonly treated with caffeine. Trials indicate that preterm babies treated with low dose
caffeine have less neurodevelopmental disabilities at 18 months. Higher doses of caffeine are often needed to
reduce AOP but the risk of this is unknown. We will study the short and long-term effects of increasing doses
of caffeine on the developing brain in a long-gestation species.
Research achievements (from final report):
Preterm birth is a major health problem worldwide. Very preterm babies are at risk of developing apnoea of
prematurity (AOP) and neurodevelopmental disability. Caffeine is the most common treatment for AOP;
clinical trials have found that preterm babies treated with low dose caffeine have fewer neurodevelopmental
disabilities at 18 months. However, higher doses of caffeine are often needed to prevent AOP but the impact of
this on the preterm brain is unknown. The aim of our study was to determine the short- and long-term effects of
higher doses of caffeine on the developing brain. Our results on the early effects of caffeine indicate, that apart
from a significant increase in brain weight following high dose caffeine treatment, there are no overt effects on
the developing brain. We are currently examining whether high-dose caffeine results in more subtle alterations
to brain development, and whether there are any adverse effects in the long-term. We are also examining the
cause of the increased brain weight.
Expected future outcomes:
Our results to date indicate that high-dose caffeine for the treatment of apnoea of prematurity is not harmful to
the developing brain, however further analysis of critical aspects of brain development is required before
definitive conclusions can be made regarding the safety of high dose caffeine.
Name of contact:
Dr Mary Tolcos
Email/Phone no. of contact:
mary.tolcos@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 1002051
CIA Name: A/Pr James Bourne
Admin Inst: Monash University
Main RFCD: Central Nervous System
Total funding: $464,418
Start Year: 2011
End Year: 2013
Grant Type: NHMRC Project Grants
Title of research award:
Developmental Plasticity in the Nonhuman Primate Visual CortexDevelopmental Plasticity in the Nonhuman
Primate Visual Cortex
Lay Description (from application):
A phenomenon that has puzzled many for a number of years is why damage to the visual brain during infancy
has far less of an impact on visual capacity than the same lesion suffered later in life. This project hopes to
uncover this mystery and see how brain 'wiring' is altered to compensate.
Research achievements (from final report):
There has long been much debate as to how the visual brain can demonstrate the capacity to recover following
an injury, especially in early life. This project led us to a better understanding of the plasticity of the visual
brain following an injury to the primary visual cortex, which generally leads to blindness. For the first time, we
demonstrate the involvement of a region of the brain known as the pulvinar and its connections with the cortex.
Hitherto research has always focussed on another region of the brain known as the lateral geniculate nucleus
but here we demonstrate that this does not play as vital a role as compared to the pulvinar. By employing novel
imaging techniques, we were able to map the connectivity of the brain before and after injury.
Expected future outcomes:
Development of tools to probe the capacity of the visual system to compensate following an injury, and
development of rehabilitation strategies to improve outcomes.
Name of contact:
James Bourne
Email/Phone no. of contact:
james.bourne@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 1006846
CIA Name: Prof Stuart Hooper
Admin Inst: Monash University
Main RFCD: Paediatrics
Total funding: $517,631
Start Year: 2011
End Year: 2013
Grant Type: NHMRC Project Grants
Title of research award:
Imaging Lung Aeration and Lung Motion following very premature BirthImaging Lung Aeration and Lung
Motion following very premature Birth
Lay Description (from application):
Using a synchrotron as an X-ray source, we will image the lungs as they aerate at birth and optimise ventilation
strategies that improve lung aeration while minimising the risk of ventilation-induced lung injury.
Research achievements (from final report):
This grant focused on identifying ventilation strategies that facilitate lung aeration and the transition to extrauterine life after birth in very preterm infants using phase contract X-ray imaging in rabbit kittens. , Finding
from this grant have provided new insights into how the process of lung aeration (establishment of a functional
residual capacity; FRC) can be facilitated in infants suffering respiratory failure immediately after birth,
particularly in very preterm infants. , Findings indicate that the type of respiratory support provided to infants
in the delivery room should begin with ventilation protocols that are designed to facilitate liquid movement
through the airways. As such, the inspiratory times should be long and measurements of expired CO2 levels
may indicate the degree and progress of aeration in the distal gas-exchange regions. , Following initial lung
aeration, which may only take 1-3 minutes, subsequent ventilation strategies can focus on facilitating gas
exchange and maintaining FRC. These include maintaining a positive pressure on the airways at end-expiration
(PEEP) to assist in preventing liquid movement back into the airways while the lung is at FRC. , These
findings provide vital information for improving the care of very preterm infants immediately after birth, with
the global aim to reduce the risk of lung injury. , Phase contract X-ray imaging movies produced demonstrating
the benefits of these ventilation strategies are exceptional communication tools and are being used as training
videos for clinicians involved in neonatal resuscitation in Australia, New Zealand and Europe. They have also
been included on the Victorian Governments Neonatal Resuscitation (Neoresus) website.
Expected future outcomes:
Positive end expiratory pressures (PEEP) are now universally used to provide respiratory support for preterm
infants in the delivery room., Clinical trail examining the benefits of a sustained inflation at birth are currently
in progress.
Name of contact:
Prof. Stuart Hooper
Email/Phone no. of contact:
stuart.hooper@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 216744
Start Year: 2002
CIA Name: A/Pr Cathy Catroppa
End Year: 2006
Admin Inst: Murdoch Childrens Research Institute Grant Type: Early Career Fellowships
(Australia)
Main RFCD: Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology)
Total funding: $127,815
Title of research award:
Long-term residual impairments in executive skills following childhood traumatic brain injury (TBI)Long-term
residual impairments in executive skills following childhood traumatic brain injury (TBI)
Lay Description (from application):
Not Available
Research achievements (from final report):
-Through-out the approval time for this project a number of aims have been achieved. All assessments for those
agreeing to participate in the 7-10 year post-injury follow-up have been completed. Data entry has also been
completed. A number of manuscripts are also in progress, with a few of these ready for submission. Key
findings have also been disseminated at both national and international conferences., -With regard to the pilot
intervention component, the intervention was developed and a number of those eligible for intervention have
completed the program, and this data is now to be analysed, and a manuscript will follow. , , Potential benefits:,
: A clearer understanding of the long-term outcomes from paediatric TBI., : A clearer understanding of the
preditors of outcome following TBI in childhood., : Development and evaluation of a pilot intervention
program aimed at improving/preventing common residual difficulties., : The potential to invite other TBI
children to take part in the intervention program.
Expected future outcomes:
- Improved quality of life for children who have sustained a TBI., - Improved quality of life for families of
children who have sustained a TBI.
Name of contact:
Cathy Catroppa
Email/Phone no. of contact:
cathy.catroppa@mcri.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 264597
Start Year: 2005
CIA Name: Prof Kerr Graham
End Year: 2009
Admin Inst: Murdoch Childrens Research Institute Grant Type: Centre of Clinical Research
Excellence
Main RFCD: Clinical Sciences not elsewhere classified
Total funding: $2,000,000
Title of research award:
Clinical Gait Analysis and Gait RehabilitationClinical Gait Analysis and Gait Rehabilitation
Lay Description (from application):
Substantial portions of the Australian population have some difficulty walking. People affected include
children with cerebral palsy, people who've had injuries playing sport and older people with Parkinson's
disease, osteoarthritis or who have had a stroke. The cost of managing arthritic conditions alone was estimated
at $2.2 Billion for 2001. Gait analysis uses high technology video cameras, force transducers, muscle activity
sensors and computers to record how people walk and is now being used more and more commonly across
Australia. The technology is very similar to that now being used to capture how people move for the movie
industry. The technology allows us a better understanding of how people are moving and therefore of what
treatments they are likely to benefit from. Melbourne now has four Gait Analysis facilities working with
different patient groups and each with an international reputation for its work. These groups have combined to
form the CCRE in Gait Analysis and Gait Rehabilitation under the leadership of Professor H Kerr Graham
(Royal Children's Hospital) and Professor Bob Iansek (Kingston Centre, Southern Health).
Research achievements (from final report):
We have acheived our goal of generating much new knowledge about walking in healthy people and in those
who have difficulty walking due to diseases such as cerebral palsy, arthritis, Parkinson's disease and stroke. We
have made significant contributions to improving the methods of measuring walking and in better
understanding the biomechanics underlying how we walk. We know more about the effects of interventions to
improve walking, such as surgery, physiotherapy and orthotics. We have trained a large group of clinicians
from medicine, surgery and allied health backgrounds to conduct clinical research within this specialised field.
We have also guided a new group of academic researchers who have completed post-graduate research higher
degrees in the disciplines of medicine, physiotherapy, biomechanics, engineering, podiatry and prosthetics. We
have led specialised educational events to train clinicians and researchers to better understand and interpret
clinical gait analysis measurements. Our team have shared this knowledge widely and effectively, through
conference presentations, specialty meetings, peer-reviewed publications and clinical seminars. Our clinical
colleagues have adopted some of this new knowledge, with translation into the clinical management and
measurement of people with gait disorders.
Expected future outcomes:
Our multidisciplinary team of trained clinical researchers will continue to contribute high quality research in
this field. Knowledge gained will translate into better outcomes for people who have difficulty walking.
Name of contact:
Professor Kerr Graham
Email/Phone no. of contact:
kerr.graham@rch.org.au
NHMRC Research Achievements - SUMMARY
Grant ID: 284518
Start Year: 2004
CIA Name: Prof Vicki Anderson
End Year: 2006
Admin Inst: Murdoch Childrens Research Institute Grant Type: NHMRC Project Grants
Main RFCD: Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology)
Total funding: $338,900
Title of research award:
Long term outcome from early childhood brain injury: 10 year follow upLong term outcome from early
childhood brain injury: 10 year follow up
Lay Description (from application):
The primary aim of this project is to further improve our understanding of the long-term consequences of
childhood traumatic brain injury (TBI). Over the past decade our research team has ascertained a sample of
children sustaining TBI, and systematically followed their progress over a 5-year period. The project has an
international reputation, and is unique in terms of length of follow-up, prospective design and representative,
well-maintained sample. Our findings challenge the traditionally held view that children are resilient and
recover fully from early brain insult. Rather, we have shown that, up to 5 years post-TBI, many children
experience impairments in physical, cognitive and behavioural function. These impairments result in
educational, vocational, social and emotional problems, limiting the child's capacity to meet developmental
expectations and achieve adequate quality of life. The implication is that these problems will lead to life-long
disability, resulting in high levels of individual, family and community burden. However, with follow-up data
limited to 5 years, there remains a possibility that ongoing developmental processes may support an extended
recovery period in childhood TBI, in comparison to the 2-year period cited in adult models. The review of this
sample, 10 years post-injury, provides an unprecedented opportunity to address this possibility and to
document recovery/outcome as children move into adolescence and adulthood. Not all children experience
problems post-injury. However, predicting individual outcome remains a significant challenge, with particular
clinical relevance to treatment and follow-up. Thus, the second aim of the proposed study is to examine factors
that contribute to recovery and outcome.
Research achievements (from final report):
This significant 10-year research project is one of the first internationally to explore outcomes of childhood
head injury in a prospective longitudinal study. The cohort in the current wave of data collection included
19/35 control and 40/96 traumatic brain injury (TBI) participants. Those who were able to be located agreed to
participate in the current wave of the study. Almost all participants consented to the complete research
protocol, providing data in the forms of Neuropsychological test results, parent-completed questionnaires, an
MRI scan, and a cheek swab for genetic testing of ApoE. In return for their assistance, all participants were
provided with the results of the MRI scan with recommendations as necessary, and a detailed report of the
Neuropsychological assessment written by a qualified Psychologist. The extensive dataset is up-to-date, and
statistical analysis and writing for publication is currently underway., , The information we obtain from the
data analysis will help both children who have already sustained a TBI and will help future cases of childhood
TBI in several ways. These include educating care providers, clinicians and the medical community broadly
about common outcomes of childhood TBI, and providing suggestions about principles to be incorporated into
clinical best-practice. Children will be better able to contribute to society in the long-term and have a better
quality of life. ,
Expected future outcomes:
As this longitudinal study provides ground-breaking research into consequences of childhood head injury it has
already established a strong international profile for the investigators, and has generated great interest within
the research and medical communities. We anticipate publishing in internationally-recognised high-impact
journals in which previous waves of this research have been reported
Name of contact:
Dr Cathy Catroppa
NHMRC Research Achievements - SUMMARY
Email/Phone no. of contact:
catroppc@tpg.com.au
NHMRC Research Achievements - SUMMARY
Grant ID: 284519
Start Year: 2004
CIA Name: Dr Peter Anderson
End Year: 2006
Admin Inst: Murdoch Childrens Research Institute Grant Type: NHMRC Project Grants
Main RFCD: Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology)
Total funding: $255,475
Title of research award:
The role of psychosocial factors on recovery following early brain insult.The role of psychosocial factors on
recovery following early brain insult.
Lay Description (from application):
Early brain insult (EBI) is a major cause of developmental delay and long-term disability. However, outcome
following EBI is variable and dependent on multiple injury-related and non-injury-related factors. To date,
most research has focussed on injury-related variables such as age at insult, nature of brain pathology, and size
and site of brain lesion. These injury-related factors predict short-term recovery following EBI, however they
have been found to account for a surprisingly modest portion of variance in long-term outcome. Thus, noninjury-related factors must also contribute to outcome following EBI. Research now suggests that psychosocial
characteristics (social status, environmental conditions, parenting characteristics, family dynamics) influence
long-term outcome following EBI, however these studies have focussed on bivariate relationships, relied on
specific patient groups limiting the generalisability of findings, and utilised small to moderate samples that are
inadequate when investigating complex interactive relationships. As a consequence, the role of psychosocial
factors on recovery following EBI is still unclear. The objective of this project is to undertake a large-scale
investigation of the independent and interactive contribution of social status, environmental conditions,
parenting characteristics and family dynamics on outcome following EBI. The aim is to identify the
psychosocial characteristics that predict outcome, mediate recovery, and buffer the impact of injury-related
factors in children with EBI. Understanding these complex inter-relationships is crucial for rehabilitation
purposes, as many psychosocial characteristics are fluid and at least partially modifiable. Based on this
project's findings we intend to devise and trial appropriately focussed intervention programs that aid recovery
and minimise long-term disabilities.
Research achievements (from final report):
The objective of this study was to undertake a large scale investigation of the independent and interactive
contribution of social status, environmental conditions, parenting characteristics, and family dynamics on longterm outcome following early brain injury. Thus the aim was to identify the psychological characteristics that
predict outcome, mediate recovery, and buffer the impact of injury-related factors in children with early brain
injury., This project has recruited a large sample of children with documented brain pathology (head injury,
prematurity, cerebral infection, tumour, hypoxia, and stroke). These children were aged 10-15 years at the time
of testing, and have a documented brain insult (CT/MRI/ultrasound) sustained more than 2 years prior to
assessment. We have recruited and assessed over 150 children, and this will be the largest sample of its kind to
assess these issues. The outcome measures used in the study assess general intelligence, adaptive functioning,
behavioural and emotional status, social skills and academic achievement. Social-demographic factors
measured to assess their role in recovery following early brain injury include parental occupation, parental
education, family income, and type of schooling (private/public). The environmental factors assessed include
the parenting characteristics, parenting mental health, family structure, family functioning, and family burden.,
While the data has been entered and clean, final analyses is only just beginning. Thus, no papers have yet been
published from this data, however this is a unique dataset and numerous papers will emanate from this study
over the next 2 years. Findings from this study will assist clinical services identify children and families at
greatest risk for poor outcome, enabling more targeted intervention and allocation of limited resources.
Expected future outcomes:
The results from this study will provide rich information as to why some children recover well following early
brain insult while others struggle. This information will then be used to devise and trial appropriately focussed
intervention programs that aid recovery and minimise long-term disabilities.
NHMRC Research Achievements - SUMMARY
Name of contact:
Dr Peter Anderson
Email/Phone no. of contact:
peter.anderson@mcri.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 334337
Start Year: 2005
CIA Name: Prof Vicki Anderson
End Year: 2007
Admin Inst: Murdoch Childrens Research Institute Grant Type: NHMRC Project Grants
Main RFCD: Mental Health
Total funding: $277,000
Title of research award:
A prospective study of concussion in children and adolescents: Diagnosis, recovery and risk factors for poor
outcome.A prospective study of concussion in children and adolescents: Diagnosis, recovery and risk factors
for poor outcome.
Lay Description (from application):
Concussion is one of the most common neurological injuries and represents a significant public health issue in
Australia. The most common consequences of concussive injuries are reduced attention, slowed response
speeds and memory impairment. These cognitive processes are critical for performing common day-to-day
activities in childhood and adolescence (e.g. acquiring new knowledge and skills, attending to school work).
Approximately 20% of concussive injuries occur during participation in organised sport. In adult populations,
there are now evidence-based guidelines for the diagnosis and management of concussion in sport. Few wellcontrolled studies exist to identify the frequency and outcome of such injuries in child and adolescent
populations, and there are currently no guidelines for diagnosis and management of concussion in children.
Further, the academic and social consequence of concussion for the child remains unknown. This study will
investigate the cognitive and behavioural outcomes of concussion in young children and adolescents and will
use this information to modify and validate currently available adult concussion diagnosis and management
paradigms for application with this population. This study will also investigate risk factors for poor outcome
following concussion in children and adolescents, and provide age-appropriate data for use in the medical,
behavioural and educational management of concussed children and adolescents. A total of 3000 children aged
between 10 and 18 years will be recruited to participate in this study. All participants will undergo a baseline
evaluation consisting of memory and attention tests, a behavioural rating scale, and measures of educational
ability. Participants parents will also provide general health and demographic information. Children who are
concussed during the year will be re-assessed within 48 hours of injury and again at 5 days, 10 days and 30
days post-injury to track recovery.
Research achievements (from final report):
This study examined the effect of concussion on cognitive functioning and physical symptoms in children and
adolescents. One of the most important achievements to come out of this study was the collection of a large
amount of data on cognitive functioning in healthy children and adolescents. This information represents a
significant contribution to the scientific literature and our results on attention and memory skills in children and
adolescents, recently presented at a major international conference, place our group at the forefront of
international research. Consistent with our original aims, we demonstrated that recovery from concussion is
different for children and adolescents than for adults as cognitive symptoms were most impaired approximately
10 days post-injury. However, our results on physical symptom endorsement were consistent with adult data,
more physical symptoms were endorsed in the days immediately after the injury. Finally, we demonstrated that
a large percentage of children who sustained a concussion during the study had previously had one or more
concussions indicating the potential risk for future injury associated with concussion. The results of this study
represent a significant contribution and have important potential for the development of evidence-based
interventions and age-appropriate guidelines governing safe return-to-play. During the course of the study we
developed close relationships with major sporting organisations, such as Cricket Victoria and Basketball
Victoria. As a result of this, our results will be incorporated into training sessions, a number of which have
already been conducted, to better educate coaches about the effect of concussion in sports.
Expected future outcomes:
We have 2 manuscripts in preparation and expect them to be in submission in the coming months. We
anticipate presenting the results at a major international conference early next year. In addition, this work has
led to the development of other research projects which have attracted high-profile international collaborators.
NHMRC Research Achievements - SUMMARY
Name of contact:
Prof Vicki Anderson
Email/Phone no. of contact:
vaa@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 384414
Start Year: 2006
CIA Name: Prof John Bateman
End Year: 2008
Admin Inst: Murdoch Childrens Research Institute Grant Type: NHMRC Project Grants
Main RFCD: Orthopaedics
Total funding: $457,518
Title of research award:
Molecular mechanisms of cartilage degeneration in osteoarthritisMolecular mechanisms of cartilage
degeneration in osteoarthritis
Lay Description (from application):
Arthritis affects 15% of the entire Australian population and 50% in people over 60. The most common form of
joint disease by far is osteoarthritis (OA). One of the central features of OA is the breakdown of the cartilage
that covers the ends of bones in joints, and this is a major determinant of the long term outcome and need for
joint replacement surgery. There are no current therapies that halt or reverse cartilage breakdown in OA. This
is largely due to our incomplete understanding of the molecular changes and pathways involved in both the
onset and progression of cartilage breakdown. Powerful new genomic approaches allow simultaneous
screening of changes in a broad profile of genes, particulalrly in humans and mice following complete
sequencing of their genomes. By applying this new technology in the earliest stages of cartilage degeneration
in OA, the role of novel genes and the pathways involved in the onset of this disease process can be discovered.
However, to investigate changes at the initiation of disease, tissue from animal rather than human joints must
be used due to the difficulty in obtaining pre-symptomatic human cartilage. In order to maximise the number of
genes screened, cartilage from a novel surgically induced model of OA in mice will be used in this study. We
have developed micro dissection and linear mRNA amplification methods to overcome inherent problems with
tissue availability from this small animal species. Successful completion of these studies will for the first time
allow identification of the complex changes that occur in early OA. An important and likely outcome of this
research will be identification of novel matrix proteins and regulatory molecules that will provide critical
information for the development of new diagnostic and therapeutic approaches to OA.
Research achievements (from final report):
This is the first study to comprehensively determine the gene expression patterns of cartilage during the
initiation and progression of osteoarthrtitis. It has identified new genes that may play a role in either the onset
or development of joint disease. Because these studies have identified possible new molecular pathways that
may be involved in OA, the information obtained in these studies has potential for the development of novel
biomarkers ans therapeutic approaches
Expected future outcomes:
The novel OA candidate genes identified in this study will be examined in detail ongoing studies. The outcome
of these studies is likely to be a more complete elucidation of OA disease mechanisms.
Name of contact:
John Bateman
Email/Phone no. of contact:
john.bateman@mcri.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 1009287
Start Year: 2011
CIA Name: A/Pr David Tingay
End Year: 2013
Admin Inst: Murdoch Childrens Research Institute Grant Type: NHMRC Project Grants
Main RFCD: Paediatrics and Reproductive Medicine not elsewhere classified
Total funding: $392,219
Title of research award:
Optimising lung protective resuscitation using a newborn premature lamb modelOptimising lung protective
resuscitation using a newborn premature lamb model
Lay Description (from application):
Premature babies are at risk of severe, and potentially long-term, lung damage. These complications can be
minimised if babies are optimally resuscitated at birth. This project will use promising new imaging
technologies to examine the influence of different strategies, using mechanical ventilators, to help inflate the
lung at birth, and their interactions with other therapies used to enhance lung maturity. It will provide new
insights into resuscitating preterm babies.
Research achievements (from final report):
Optimising the aeration of the fluid-filled preterm lung during the very first breathes is essential for immediate
and longterm survival. At present this is hampered by a lack of practical tools to assist clinicians understand
how the lung is responding to treatments at birth. This project compared different strategies designed to aerate
the preterm lung at birth including a new strategy developed by our team that intentionally exploited the
mechanical behaviour of the chest. In doing so we developed new methods of monitoring the preterm lung at
birth. These methods for the first time provided insight into the complex interactions between regional
volumetric mechanical and injury behaviour of the lung. Our studies demonstrated that our new technique to
support the preterm lung resulted in better oxygenation lung volume and mechanics without increasing lung
injury. Furthermore we demonstrated that this method upregulated the effects of other lung therapies at birth.
We also identified why traditional methods of aerating the lung at birth may not always be successful and
developed a new method of applying these strategies. These studies provide new insights into how we
understand the critical process of lung aeration at birth and offer the potential for new treatments that may
improve outcomes for this vulnerable population.
Expected future outcomes:
Futher basic science studies to refine respiratory strategies at birth and identify the best method of monitoring
lung function at birth. This work will then inform clinical physiological trials with the view to larger effect
trials.
Name of contact:
Dr David Tingay
Email/Phone no. of contact:
david.tingay@rch.org.au
NHMRC Research Achievements - SUMMARY
Grant ID: 437205
CIA Name: Prof Peter Drummond
Admin Inst: Murdoch University
Main RFCD: Peripheral Nervous System
Total funding: $345,473
Start Year: 2007
End Year: 2009
Grant Type: NHMRC Project Grants
Title of research award:
Involvement of adrenergic receptors in neuropathic painInvolvement of adrenergic receptors in neuropathic
pain
Lay Description (from application):
After nerve or tissue injury including burns, some people will suffer from a condition called neuropathic pain.
This is a condition where chronic pain is endured, often totally unrelated to the initial injury or induced by
events that would normally not be painful. Our project will determine whether this abnormal pain response is
due to an abnormal communication between the nerves that carry pain signals (sensory nerves) and nerves that
form part of the sympathetic nervous system, which is part of autonomic (or involuntary) nervous system. We
believe that this abnormal communication is due to an increase in the expression of special receptors called
adrenergic receptors, on the sensory nerves. Our project will look at these receptors in the skin of animals that
have had pain conditions induced, and also in skin samples from patients who suffer from neuropathic pain that
can be classified as sensitive to sympathetic stimulation. By better understanding how neuropathic pain is
derived, we can open the door to novel treatment approaches in these difficult to treat conditions.
Research achievements (from final report):
Neuropathic pain is a difficult and costly health problem. It is a common condition that is often misdiagnosed
and difficult to treat because we do not understand the primary factors that drive the disease. The studies in this
project concentrated on clarifying the biological basis of a link between the pain processing system and the
sympathetic nervous system which is thought to contribute to certain forms of neuropathic pain. , We
discovered that pain-signalling nerves contain a molecular target for noradrenaline, the chemical messenger
released by the sympathetic nervous system, that controls blood flow through the skin. We also found that
activation of this molecular target, termed the alpha-1 adrenoceptor, increases the excitability of pain-signalling
nerves and ultimately sends pain messages to the brain. In addition, we identified an increase in the expression
of these receptors on nerve fibres that survived an injury to the sciatic nerve. , Together, these findings help to
explain the link between the pain-processing system and the sympathetic nervous system. They also introduce a
novel target for analgesia that could potentially alleviate pain in the skin of patients with neuropathic pain.
Expected future outcomes:
The next step is to find out whether an antagonist to the alpha-1 adrenoceptor suppresses pain when taken
orally or when applied in a topical preparation to the skin of patients with neuropathic pain. Topical application
is the preferred aproach as this would avoid unwanted side-effects of oral medication.
Name of contact:
Dr Peter Drummond
Email/Phone no. of contact:
p.drummond@murdoch.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 157305
Start Year: 2001
CIA Name: A/Pr Julie Bernhardt
End Year: 2004
Admin Inst: National Stroke Foundation
Grant Type: Early Career Fellowships (Australia)
Main RFCD: Public Health and Health Services not elsewhere classified
Total funding: $127,599
Title of research award:
Walking handicap and falls in stroke survivorsWalking handicap and falls in stroke survivors
Lay Description (from application):
Not Available
Research achievements (from final report):
This research award has led to the development of a new model and direction of stroke rehabilitation research
with the potential to: 1) unite researchers and clinicians from across Australia; 2) answer an important and
timely research question about stroke rehabilitation models of care and 3) reduce the burden of stroke
experienced by patients, carers and the broader community. The preliminary work for this research program led
to new knowledge about physical activity patterns of patients very early after stroke. This was published in the
prestigous journal Stroke. After identifying the routine high levels of bed rest (and low levels of activity) early
after stroke, we worked closely with collaborators in Norway to develop a very early model of rehabilitation
suitable for testing here in Australia. We chose Norway because this research group have demonstrated
consistently better outcome after stroke than other stroke units worldwide. Furthermore, preliminary evidence
from their centre suggests that very early rehabilitation is a major contributor to these outcomes. In the past 2
years we have: 1) gathered together a small team to work on AVERT (A Very Early Rehalitation Trial); 2)
developed the trial methods for AVERT ensuring best practice randomised controlled trial methods are
employed, 3) obtained approval from two hospitals to conduct the trial, 4) commenced the Phase 2 safety and
feasibility study, with 60 patients recruited to date, 5) obtained over $200,000 in funding from a range of
sources and 6) developed 10 collaborative centres here in Australia and a collaborative centre in Glasgow UK,
all interested in conducting Phase 3 of the trial at their hospital. The preliminary work from this research
program has been presented at National and International conferences, with two further publications in
preparation. Once Phase 3 funding is secured, we will conduct the largest stroke rehabilitation trial (with
economic evaluation) ever over the coming 5 years.
Expected future outcomes:
We expect AVERT to be a landmark study in the field of stroke rehabilitation research, regardless of outcome.
If early rehabilitation reduces death and dependency, leads to fewer and less severe complications, better
quality of life for patients and is cost effective (as we hypothesise), then we expect the practice to be adopted
across Australia, ultimately reducing the buden of stroke.
Name of contact:
Julie Bernhardt
Email/Phone no. of contact:
J.Bernhardt@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 388920
Start Year: 2006
CIA Name: Dr Craig Harrison
End Year: 2008
Admin Inst: Prince Henry's Institute of Medical Research
Grant Type: NHMRC Project Grants
Main RFCD: Endocrinology
Total funding: $507,271
Title of research award:
Activin type II receptor antagonists: mechanism of action and biological applicationsActivin type II receptor
antagonists: mechanism of action and biological applications
Lay Description (from application):
Activin is a member of the TGF- family of growth and differentiation factors. Over-expression in mice leads
to muscle and liver wasting, scarring during wound healing, disturbances to the reproductive system and
various endocrine disorders. Activin's biological activity is promoted by its binding in series to two receptors
termed Type I and II. Previous studies by this investigator have shown that selective modification of activin's
protein structure can result in activin forms (in this instance called activin-M108A) which bind to Type II
receptors but fail to promote binding to the Type I receptor. This has led to the hypothesis that activin-M108A
may compete for native activin binding to Type II receptors and thus prevent activin's recruitment of the Type I
receptor with the consequence that activin's biological activity is inhibited. It is proposed to test this
hypothesis by producing sufficient amounts of activin-M108A and testing its inhibitory effects in several
mouse models of liver damage, muscular degeneration and ovarian and testicular disease. If activin-M108A, or
related modified forms of activin, decrease the morbidity and mortality associated with these murine diseases,
then we envisage that these activin type II receptor antagonists will also be beneficial for the treatment of
related human conditions.
Research achievements (from final report):
Activins are important regulators of diverse cellular functions, differentiation and proliferation that, of
necessity, are precisely constrained by multiple mechanisms. Despite these constraints a deregulated activin
signalling pathway has been implicated in a variety of disorders, including fibrosis, cachexia and cancer. We
developed the first activin type II receptor antagonist (activin-M108A) and showed that it is capable of
blocking signalling in vitro by activin and the related protein, myostatin. However, when assessed in the rat
pituitary cell culture system, activin-M108A was a poor antagonist of follicle stimulating hormone (FSH)
release and in our preliminary animal studies, no suppression of FSH was observed in ovariectomized rats
(despite a robust suppression of FSH observed upon addition of the known activin antagonist, inhibin). The
major reason for the lower than anticipated potency of activin-M108A is its significantly reduced affinity for
the activin receptor complex. Therefore our primary objective of utilizing activin-M108A as an
activin/myostatin antagonist in vivo was not realized. Subsequent studies, however, have made important
contributions to the understanding of the mechanism of action of key activin inhibitory molecules, including
follistatin, betaglycan and inhibin. In addition, we have developed second generation activin antagonists that
are more effective than activin-M108A. These compounds could be used to block activin signalling in disease
models.
Expected future outcomes:
Our continuing studies have generated a more specific and potent activin A antagonist. Based on these studies,
we are also developing reagents that will specifically block other TGFbeta proteins. Given the importance of
TGFbeta proteins in development and the maintenance of tissue homeostasis, and their dysregulation in many
disease pathologies, this will be a significant achievement.
Name of contact:
Craig Harrison
Email/Phone no. of contact:
craig.harrison@princehenrys.org
NHMRC Research Achievements - SUMMARY
Grant ID: 138711
Start Year: 2001
CIA Name: Dr James Smeathers
End Year: 2003
Admin Inst: Queensland University of Technology Grant Type: NHMRC Project Grants
Main RFCD: Biomechanical Engineering
Total funding: $185,665
Title of research award:
QUANTITATIVE ASSESSMENT OF LOOSENING IN HIP ARTHROPLASTIES USING MECHANICAL
VIBRATION DIAGNOSTICSQUANTITATIVE ASSESSMENT OF LOOSENING IN HIP
ARTHROPLASTIES USING MECHANICAL VIBRATION DIAGNOSTICS
Lay Description (from application):
Recent advances and improvements made to the mechanical design of artificial joints have led to greater
strength, fatigue life and wear resistance. However, this extension to the working life of joint replacements has
led to patients becoming increasingly vulnerable to the problem of joint loosening. There are over 500 000 hip
joint replacements performed every year, on a worldwide basis. Of these 7 to 13% will require revision surgery
because of loosening at some stage of their working life. This is becoming a major concern to health services
around the world since revision surgery is associated with a higher risk to the patient and costs are far greater
than for the primary operation. Current diagnostic techniques using radiographic imaging are both invasive and
lack diagnostic accuracy. The ability to detect joint loosening and to discriminate between the various causes of
joint loosening following arthroplasty is of great importance to the success of subsequent care plans. This study
will be the first in the world to assess the validity of a new diagnostic test that uses low energy mechanical
vibration to quantify the degree of loosening in both components of the implanted hip joint. Once the technique
has been proven it could readily be extended to evaluate the degree of fixation of other implanted prostheses
used to replace the knee, ankle or joints of the upper limbs.
Research achievements (from final report):
This research program has significantly advanced the way that loosening of artificial hip joints is detected by
using low energy mechanical vibration to provide a safe additional means of evaluating the integrity of an
implant in the human body. The significance of this relates to the 500 000 hip joint replacements that are
performed worldwide annually. Unfortunately, up to 8% of these implants will suffer from aseptic loosening
which, is thought to be caused by tissue reaction to wear debris and resorption of the supporting bone. There is
growing concern over the increasing numbers of artificial joints that are failing by loosening due impart to the
large numbers in service and the trend to earlier implantation in younger more active patients. It is still difficult
to diagnose aseptic joint loosening with current clinical imaging techniques where loosening is confirmed by a
combination of invasive radiographic techniques, radio-opaque dyes injected into the joint space, pain
provocation tests and ultimately, physical assessment at the time of surgery. Hence this research evaluates a
complimentary diagnostic technique that is based on mechanical vibration to detect structural changes within
the human body. The principles of vibration based monitoring previously developed by engineering and
aerospace industries to detect failure in machinery is now being applied to the human body and the problem of
loosening in artificial joints. The potential of this novel application to the clinical problem of artificial joint
loosening has been examined by this research project under extensive laboratory tests and early clinical trials.
In principle, this additional diagnostic test will help improve the health of Australians through improved
accuracy of diagnosis and efficiency of surgical care by assisting the surgeon to make better informed decisions
on whether or not to reoperate on the joint and how to optimise the timing of revision procedures.
Expected future outcomes:
In the longer term knowledge gained from this research coupled with improvements in technology will enable a
clinical diagnostic device, for detecting loosening of artificial joints, to be manufactured in Australia and
marketed throughout the world. The diagnostic principles of this system will also have relevance to a wide
range of other structural problems and discipline areas.
Name of contact:
James Smeathers
NHMRC Research Achievements - SUMMARY
Email/Phone no. of contact:
j.smeathers@qut.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 390100
Start Year: 2005
CIA Name: Prof Zee Upton
End Year: 2006
Admin Inst: Queensland University of Technology Grant Type: NHMRC Development Grants
Main RFCD: Medical Biotechnology
Total funding: $156,870
Title of research award:
Pre-clinical assessment of novel growth factor complexes as a topical agent in the treatment of deepPre-clinical
assessment of novel growth factor complexes as a topical agent in the treatment of deep
Lay Description (from application):
Healing of deep burns, unlike that of superficial injuries, often resolves with scarring. Scarring is reduced with
rapid closure of burns. The CIs have discovered and patented novel growth factor complexes that stimulate the
growth and migration of keratinocytes, cells derived from skin. Hence these complexes hold therapeutic
potential for wounds that require rapid closure such as deep burns. This application will provide pre-clinical,
proof-of-principle data to facilitate future patient trials.
Research achievements (from final report):
This preclinical study follows a trial completed in early 2005 which successfully demonstrated that VitroGro®
complexes significantly accelerate skin healing and appears to substantially reduce scar tissue formation,
providing confidence about the potential of VitroGro® as a wound treatment., The most recent trial was
conducted to prove 2 things. Firstly that recombinant VitroGro® works as efficiently as the VitroGro® made
from conventional purified proteins, and secondly to determine the optimal dosage in preparation for clinical
trials planned for 2007. Both objectives were successfully achieved and recombinant VitroGro® performed as
expected and the pre-clinical dose study found that there was no statistically significant differences in the
results obtained with the range of VitroGro® doses tested . Therefore the dosage of VitroGro® used during
both the first and this latest study will be employed in the upcoming human trials and is anticipated to be
effective., In addition, the unexpected finding of the dosage study was the positive and statistically significant
results for the reduction of wound contraction when treated with VitroGro®. Wound contraction is a major
problem in the treatment and healing of wounds, particularly paediatric burns and is the most common reason
for corrective surgery required after burn injuries. In this regard, VitroGro® has been shown to significantly
reduce wound contraction in the pre-clinical study. Importantly, there are currently no approved treatments to
minimize wound contraction in adult or paediatric patients and more than half the operations performed on
children by Associate Professor Roy Kimble are due to contractures.
Expected future outcomes:
The industry partner, Tissue Therapies, intends to supplement this data with a further preclinical trial. This
follow-up study will provide the final data required on a small number of endpoints and will complement the
data generated through the trial reported here. Together this will be used to prepare for the human studies
planned for 2007.
Name of contact:
Professor Zee Upton
Email/Phone no. of contact:
z.upton@qut.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 390102
Start Year: 2006
CIA Name: Prof Helen Edwards
End Year: 2008
Admin Inst: Queensland University of Technology Grant Type: NHMRC Project Grants
Main RFCD: Therapies and Therapeutic Technology
Total funding: $374,159
Title of research award:
Identifying the relationship between biochemical markers and healing in chronic leg ulcers treated with
compressionIdentifying the relationship between biochemical markers and healing in chronic leg ulcers treated
with compression
Lay Description (from application):
Chronic leg ulcers are a significant cause of pain, immobility and decreased quality of life for 1 - 3% of the
over 60 years age group. The condition is difficult to heal and commonly becomes a long term problem,
costing the Australian health care system over $500 million / year. Additional costs to the community include
loss of productivity and social support systems necessary for people with limited mobility. As the number of
people aged over 65 years is expected to double in the next few decades, this problem will become increasingly
significant. Most chronic leg ulcers are caused by venous disease, and compression bandage therapy is the
accepted standard treatment. However, there is little information available on the cellular responses associated
with compression treatment and how they promote wound healing. The project proposed here will examine the
cellular responses to compression and investigate the relationships between these cellular responses and wound
healing. Knowledge gained from the study will provide valuable information for improved techniques to
promote wound healing, improved ulcer healing rates, informed decisions on wound care treatment, improved
qualtiy of life and reduced health care costs.
Research achievements (from final report):
Chronic leg ulcers are a significant cause of pain and immobility for older adults and care for chronic wounds
costs 1-2% of total health expenditure. The ulcers are difficult and slow to heal and knowledge of the
biochemical processes involved in wound healing is poor. Results from this study have provided new
information on the associations between biochemical changes at the wound site, progress in wound healing,
and type of compression therapy. , The discovery of relationships between uric acid levels and wound severity
are likely to lead to development of reliable, non-invasive point of care diagnostics to monitor the onset,
prognosis and progress of chronic venous leg ulcers. Importantly, this study has generated new evidence on the
comparative effectiveness of two different types of compression therapy for healing venous leg ulcers.
Although compression therapy is the gold standard treatment for venous leg ulcers, it is often associated with
high costs and a need for specialised expertise to apply correctly, which may inhibit commencement of
treatment. Results from this study on the relative effectiveness of two compression types provides health
professionals and consumers with evidence on a greater range of effective compression therapies. This together
with the development of specific biochemical diagnostic tools would transform current wound management by
guiding clinical decisions and enabling treatments to be tailored to differing needs and available resources. This
information will promote increased use of compression treatment and improved healing for those suffering
with chronic leg ulcers.
Expected future outcomes:
New point of care diagnostics/therapies to promote healing in chronic wounds, Improved healing rates and
quality of life for those who suffer with chronic leg ulcers, Reduced health care costs associated with improved
healing rates
Name of contact:
Prof. Helen Edwards
Prof. Helen Edwards
NHMRC Research Achievements - SUMMARY
Email/Phone no. of contact:
h.edwards@qut.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 443210
Start Year: 2007
CIA Name: A/Pr Graham Kerr
End Year: 2009
Admin Inst: Queensland University of Technology Grant Type: NHMRC Project Grants
Main RFCD: Geriatrics and Gerontology
Total funding: $680,793
Title of research award:
Dynamic postural stability and falls prediction in older people during walking in real-world
environments.Dynamic postural stability and falls prediction in older people during walking in real-world
environments.
Lay Description (from application):
The increased occurrence of falls with advancing age (33-50% of people aged >65 years) is a significant cause
of mortality (1014 deaths in 1998), morbidity, and disability, affecting not only the individuals concerned, but
the health care system (45,069 fall related hospitalizations in 1998 in Australia) and the broader community
(National falls Prevention Initiative, 2004). Although there are a number of falls risk tests, most rely on
determination of body sway while standing when the body is static rather than in motion. Given that up to 70%
of falls occur during walking and performing transfers, there is a clear need to develop tests of falls risk
prediction that incorporate indices of postural stability measured during more dynamic activities. Test
development needs to be underpinned by clear evidence of how age-related sensory and motor deficits affect
postural stability during walking. The studies outlined in this application will develop and utilise new
accelerometer-based technologies to determine the fundamental mechanisms underlying balance control during
walking in older people. Specifically, this project will aim to develop a clear understanding of how changes in
factors as vision, neuromuscular function (strength, stiffness) and proprioception contribute to the overall
decline in stability and balance during walking in older people. Combined with physiological assessment
measures developed by the research team, the research will allow the development of a more definitive
predictive test of stability and falls risk. This test will be able to be used by health professionals for assessment
of older people to determine the most effective therapeutic and/or exercise interventions to target those
individuals at risk. This technology will also be adaptable to a biofeedback device to allow individuals to
monitor their own stability.
Research achievements (from final report):
This research has developed new accelerometer-based technologies and innovative tests of trunk stiffness to
determine the fundamental mechanisms underlying balance control during walking and standing in older
people. These tools were used to investigate critical issues that have an impact on dynamic postural control and
falls risk in older people. In addition, visual factors that contribute to increased risk of falls were examined,
particularly those related to decreased contrast sensitivity and visual blur. The research was extended to include
people with neurodegenerative disease, partcularly Parkinson's disease, to determine similarities and
differences in falls rick factors with older people. This research has resulted in precitive tests for falls risk in
older people.
Expected future outcomes:
This research will provide prospectively validated accelerometer systems, in combination with physiological
parameters, for more accurate prediction of older people at risk of falling. The results will also inform
evidenced based best-practice approaches for interventions to reduce the risk of falls in older people and people
with neurodegenerative diseases.
Name of contact:
Graham Kerr
Email/Phone no. of contact:
g.kerr@qut.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 497265
Start Year: 2008
CIA Name: Dr Benjamin Goss
End Year: 2010
Admin Inst: Queensland University of Technology Grant Type: NHMRC Development Grants
Main RFCD: Orthopaedics
Total funding: $85,933
Title of research award:
The Next Generation of Biomaterials; In Vivo Assessment of Lumbar Spinal Fusion Biodegradable Interbody
CagesThe Next Generation of Biomaterials; In Vivo Assessment of Lumbar Spinal Fusion Biodegradable
Interbody Cages
Lay Description (from application):
Back pain represents one of the major health and economic problems facing the western world. Surgery is an
inevitable outcome for many sufferers and involves the implantation of metallic rods screws, plates or cages.
Biodegradable implants have theoretical advantages, but until now no material has existed that can sustain he
rigours of implantation into a load bearing site. We have developed such a material which will lead to
improvements in the treatment of many orthopaedic conditions.
Research achievements (from final report):
Back pain represents one of the major health and economic problems facing the western world. In Australia
nearly 80% of adults will suffer with over $1.2 billion spent on medical intervention and losses in productivity
of over $8 billion. A significant proportion of reported back pain will require surgery. Non-degradable implants
are commonly used to provide stability in spinal fusion. These materials a have major disadvantages including
implant stress shielding and long term problems associated with subsidence, migration and fracture.
Biodegradable spacers have been suggested as a potential solution to many of these problems, however the
current generation of biomaterials have unsatisfactory mechanical properties and degradation profiles for any
load bearing application., , In this project we examined a new class of biodegradable polymers in spinal fusion.
Despite promising data in some experiments, contamination of implants during the manufacture resulted in a
variable response to the implant. Despite being unable to show unequivocally that this material will make
appropriate orthopaedic devices we were able to show that the adverse reactions were unrelated to the
biomaterial composition. We have since successfully tested this material in applications where the implant is
manufactured by different techniques.
Expected future outcomes:
This material is being tested in other applications including advanced drug delivery systems and bone graft
extenders
Name of contact:
Ben Goss
Email/Phone no. of contact:
b.goss@qut.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 497266
Start Year: 2008
CIA Name: Prof Zee Upton
End Year: 2010
Admin Inst: Queensland University of Technology Grant Type: NHMRC Development Grants
Main RFCD: Clinical Sciences not elsewhere classified
Total funding: $125,041
Title of research award:
Development and pre-clinical evaluation of a novel wound dressing treatment for chronic ulcersDevelopment
and pre-clinical evaluation of a novel wound dressing treatment for chronic ulcers
Lay Description (from application):
Chronic leg ulcers are a common, painful and costly reality for many Australians, impacting on sufferers'
mobility, social interactions and overall quality of life. This research is directed at developing a novel costeffective wound dressing for treatment of this condition. This will be achieved through neutralising the ulcer's
toxic proteolytic environment through an interactive wound dressing. This then will allow the body's own cells
to promote wound healing.
Research achievements (from final report):
Chronic wounds, such as burns and venous leg ulcers, are well-known challenges in medical research. The cost
resulting from the treatment of these wounds is significant. This project proposed a novel, device-oriented
approach for the treatment of chronic wounds. The goal of this research is to inactive the proteases in the
wound fluid after the fluid is absorbed away from the actual wound bed. In this situation, the proteases required
for healing associated functions within the upper cellular layers of the wound bed remain active and available.
In order to achieve this, the project firstly conducted critical research on the development of a novel matrix
matalloproteinase (MMP) inhibitor, and then tethered this developed inhibitor to a carrier, a polymer hydrogel.
It is confirmed that the inhibitor itself demonstrated effective MMP inhibition in both standard active MMP
solutions and in chronic wound fluid extracted from patients who suffer from venous leg ulcers. When the
tethered inhibitors were tested against chronic wound fluid, we observed significant inhibition in proteolytic
activity suggesting our approach may prove useful in rebalancing MMPs within chronic wounds. The CIs have
protected this novel MMP inhibitor via a Provisional Patent application, which allows us to further conduct
critical product development and proof-of principle pre-clinical studies for the enhanced remediation of chronic
wounds.
Expected future outcomes:
We will conduct further product development and pre-clinical studies based on the outcomes from this project.
We expect that a novel, effective, reliable wound dressing product will be available in the near future to
enhance remediation of chronic wounds, thereby benefitting people suffering from chronic wound in Australia
and world-wide.
Name of contact:
Professor Zee Upton
Email/Phone no. of contact:
z.upton@qut.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 497267
Start Year: 2008
CIA Name: Prof Zee Upton
End Year: 2010
Admin Inst: Queensland University of Technology Grant Type: NHMRC Development Grants
Main RFCD: Biochemistry and Cell Biology not elsewhere classified
Total funding: $163,578
Title of research award:
Development and Pre-Clinical Evaluation of a Silicone Dressing for Scar RemediationDevelopment and PreClinical Evaluation of a Silicone Dressing for Scar Remediation
Lay Description (from application):
This research is aimed at exploiting advanced polymers as a new therapy for patients with burn related scars, as
well as people who are genetically predisposed to scarring due to abnormal healing. In order to progress to
clinical trials, the technology needs to be tested on an animal scar model. Successful outcome of these tests will
allow the industry partner, Tissue Therapies, to proceed with a clinical trial, paving the way to a therapeutic
product available for scar treatment.
Research achievements (from final report):
Scarring is a unavoidable product of wound repair and can occur as a result of injury to the dermal layer of skin
from trauma (e.g. burns, cuts) and elective procedures. Each year over 100 million scars are acquired
worldwide, often causing significant pain to the patient as well as psychological damage in some cases. This
project was aimed at testing how lipid-like silicone oils can be used to treat severe scars known as hypertrophic
scars which are red and raised and can cause limited mobility and pain to the patient. What we have discovered
is that these silicones are mildy toxic to the cells found in skin and cause cell death in a controlled manner,
similar to some of the natural processes in the body involved in normal tissue turnover. When these silicones
are applied in low doses to cultured skin offcuts donated by patients undergoing abdominoplasty they can cause
thinning of the skin and at high doses can cause separation of the epidermis and the dermis. Thus, these
silicones may be used as a topical treatment for scars as an alternative to current treatments such as injections
of the toxic drug, bleomycin. We have also found that these silicones may be useful in the treatment of other
skin disorders such as psoriasis which is a condition characterised by hyperproliferative cells within the
epidermis. Psoriasis affects approximately 2% of the population and can be managed but not cured using
topical or systemic treatments or exposure to UV light.
Expected future outcomes:
We currently own the intellectual property covering the use of amphiphilic silicone oils on scars and are
continuing to explore commercial opportunities using the results generated from this grant. We expect that if
this product is commercialised it will offer the many patients suffering severe scars an alternative and
potentially more effective treatment.
Name of contact:
Prtofessor Zee Upton
Email/Phone no. of contact:
z.upton@qut.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 497268
Start Year: 2008
CIA Name: Prof Adekunle Oloyede
End Year: 2011
Admin Inst: Queensland University of Technology Grant Type: NHMRC Development Grants
Main RFCD: Biomechanical Engineering
Total funding: $230,633
Title of research award:
Development of a smart arthroscopy system and prototype probe for joint tissuesDevelopment of a smart
arthroscopy system and prototype probe for joint tissues
Lay Description (from application):
This project relates to the ever growing use of arthroscopy in the management of joint defects. An innovative
probe that will combine all the molecular, microstructural and biomechanical characteristics of joint articular
cartilage and bone for the purposes of diagnosis, treatment, treatment-related decisions, comparison of the
effectiveness of treatment methods and post treatment evaluation will be developed. This system will produce
spin-offs for arthroscopy of other soft tissues and bodies.
Research achievements (from final report):
The aim of the research was to conduct further research into the assessment of cartilage viability. The expected
outcome was a prototype proof-of-concept (POC) probe that combines near infrared, ultrasound and
mechanical loading technologies into one easily applied probe. The potential benefit is an advancement in the
field of arthroscopy that removes subjectivity and hence unnecessary surgery for patients with related cost
reduction to the national health budget. The innovative POC probe has been developed with a new interface
that both controls data acquisition and all related analysis of raw data, outputting parameters that enable precise
surgical decisions. The POC probe was demonstrated on December 4th 2009., The new stand-alone graphical
user interface (GUI) application was built in the MATLAB environment. It implements multivariate statistical
protocols such as partial least squares regression (PLSR), principal component analysis (PCA) and principal
component regression (PCR) from the statistics toolbox. Accepting raw data in any of three different formats
(.csv, .xls, .txt), this application implements the necessary statistical protocol based on user preferences and
outputs the required parameter for assessment.
Expected future outcomes:
Further resolution of the ultrasound and NIR spectra information for precise mapping of layer-by-layer
property of a piece of cartilage. We are also going to incorporate the new IP system that has been developed
into an existing arthroscope so that we can carry out preliminary clinical tests. It has also been decided that the
IP would be better protected by secrecy with blackbox implementation.
Name of contact:
Prof. Adekunle Oloyede
Email/Phone no. of contact:
k.oloyede@qut.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 553028
Start Year: 2009
CIA Name: Prof Zee Upton
End Year: 2012
Admin Inst: Queensland University of Technology Grant Type: NHMRC Project Grants
Main RFCD: Surgery
Total funding: $275,203
Title of research award:
Improved ex-vivo culture of keratinocytes for clinical applicationsImproved ex-vivo culture of keratinocytes
for clinical applications
Lay Description (from application):
Skin cells grown for clinical applications currently require animal-derived cells and/or non-defined products
for their expansion in the laboratory; these reagents can potentially infect patients who receive these therapies.
This project will identify the essential components provided by these reagents and develop a fully synthetic and
defined culture system. This improvement will provide safer, cost-effective grafts and cell-based therapies that
will benefit patients suffering burns and wounds.
Research achievements (from final report):
The culture of human skin cells in a laboratory requires the use of animal products (xenobiotics) to supplement
the media and as a compatible surface for the cells to grow on. The use of animal products brings a high risk of
disease transmission from animals to humans. This risk greatly limits the use of skin cells in a clinical setting
for skin regeneration treatments that are required following burn and scarring injuries. Therefore, this project
aimed to develop a way to grow human skin cells without the use of animal products. We utilised proteonomic
based techniques to examine the current culture system. We determined what products the animal cells produce
that enable the human cells to grow in the laboratory. We then utilised human or recombinant versions of these
supplements to develop a culture system which enabled the human skin cells to be grown without the use of
animal products. We were able to culture the human skin cells in this culture system for short periods without
compromising the health of the skin cells. The successful removal of all xenobiotic and non-defined materials
and their replacement with recombinant and synthetic reagents will allow the improved, safe manufacture of
keratinocyte-based cell therapies to treat burns, wounds and chronic ulcers. The outcomes from this project will
therefore facilitate delivery of safe regenerative and therapeutic keratinocyte-based treatments to the Australian
and global communities.
Expected future outcomes:
The techniques developed in this project will be expanded to enable safer, faster and longer culture of human
skin cells. Potential future applications include the treatment of burn and scarring victims.
Name of contact:
Professor Zee Upton
Email/Phone no. of contact:
z.upton@qut.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 390400
Start Year: 2006
CIA Name: Prof R. Douglas McEvoy
End Year: 2008
Admin Inst: Repatriation General Hospital, Daw Park Grant Type: NHMRC Project Grants
Main RFCD: Respiratory Diseases
Total funding: $466,765
Title of research award:
Experimental Investigation of Driving Impairment in Obstructive Sleep ApneaExperimental Investigation of
Driving Impairment in Obstructive Sleep Apnea
Lay Description (from application):
Obstructive Sleep Apnea (OSA) affects 2-4% of the adult population. Repetitive throat obstructions at night
lead to sleep disturbance and oxygen deprivation which in turn lead to excessive daytime sleepiness and poor
concentration. Studies in severely affected OSA patients have demonstrated driving simulator performance
impairment and a 2-7 fold increased rate of motor vehicle accidents. Current data suggest that up to 50,000
MVAs may be caused each year in Australia by OSA. While driving impairment and increased crash risk in
severe OSA seems clear it is not known whether patients with mild-moderate disease are also affected. This is
an important question since patients with mild-moderate disease make up the great majority of OSA sufferers
and therefore potentially pose the greatest concern for overall public safety. This study will determine whether
mild-moderate, as well as severe, OSA is associated with driving impairment. The study will also determine
how partial sleep deprivation and low dose alcohol impact on driving performance in OSA. These two
behaviours are considered part of the "norm" for modern societies, yet we recently showed that they act
synergistically to markedly impair driving in healthy subjects. We suspect that years of prior sleep disturbance
and oxygen deprivation will render OSA sufferers more vulnerable to the effects of these additional central
nervous system insults. Finally, we will determine how well driving impairment in severe OSA responds to
nose mask CPAP treatment. We will find out what minimum level of treatment adherence is needed to produce
significant improvement and whether driving impairment is ever truly reversed. The information obtained in
this study will inform and significantly improve patient care,"fitness to drive" guidelines and driver safety
campaigns.
Research achievements (from final report):
This research award has aided in the development of knowledge of the effects of obstructive seep apnoea on
driving performance. The effects of additional sleep restriction and low-dose alcohol on OSA patients has been
explored with the finding that OSA patients are more vulnerabe to these additonal stressors. The effectiveness
of CPAP treatment in improving driving performance and reducing vulneraility to sleep loss and alcohol has
been assessed with the conclusion that treatment of OSA is partially effective in improvng driving performance
and alleviating OSA dependent vulnerability to sleep restriction and alcohol. These findings are of high clinical
relevance and provide clinicians with evidence supporting the need to warn patients of dangers of driving under
conditions of moderate sleep loss and low-dose alcohol, which occur commonly in society. These findings also
stengthen the case for prompt diagnosis and treatment of OSA patients in order to improve public health and
traffic safety.
Expected future outcomes:
Creating pulic awareness of these findings through media and journal publications which may lead to
alterations in clinical practice and public policy to improve patient healthcare and safety.
Name of contact:
Professor Doug Mcevoy
Email/Phone no. of contact:
doug.mcevoy@health.sa.gov.au
NHMRC Research Achievements - SUMMARY
Grant ID: 555427
CIA Name: Prof Marc Cohen
Admin Inst: RMIT University
Main RFCD: Oriental Medicine and Treatments
Total funding: $416,301
Start Year: 2009
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
Randomised controlled trials of acupuncture vs. pharmacotherapy for acute pain relief in emergency
departmentsRandomised controlled trials of acupuncture vs. pharmacotherapy for acute pain relief in
emergency departments
Lay Description (from application):
The proposed study involves three separate randomised controlled trials comparing acupuncture alone and
acupuncture along with drug therapy, to drug therapy alone in providing pain relief for patients presenting to
the Northern Hospital and Epworth Hospital Emergency Departments with acute back pain, migraine and ankle
sprain. The research will help determine if acupuncture is safe, effective and acceptable to patients.
Research achievements (from final report):
This research involved three concurrent randomised controlled trials examing acupuncture alone, acupuncture
plus pharmacotherapy and pharmacotherapy alone in the provision of analgesia for patients presenting to
emergency departments with back pain, migraine and ankle sprain. More than 539 patients were recruited from
four separate hospital emergency departments including the Alfred Hospital, Northern Hospital, Epworth
Hospital and Cabrini Hospital. The research found that acupuncture was equivalent and not inferior to
pharmacotherapy in providing analgesia for patients presenting to emergency deprtments with back pain,
migraine and anke sprain. This study has demonstrated that acupuncture can be successfully provided to
patients presenting with pain in an acute emergency department setting and that the analgesia provided by
acupuncture has similar efficacy as that provided by drug therapy. This study suggests that acupuncture may
provide an effective non pharmacological option for emergency department patients and further suggests that
training in acupuncture may be a useful adjunct to emergency physician training.
Expected future outcomes:
Further analysis of the data will compare the adverse events, patient satisfaction and health resource utilization
between the three study groups and determine if acupuncture provides any benefit in terms of patient
satisfaction, safety and assocaited healthcare costs.
Name of contact:
Prof Marc Cohen
Email/Phone no. of contact:
marc.cohen@rmit.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 555429
CIA Name: Prof Marc Cohen
Admin Inst: RMIT University
Main RFCD: Geriatrics and Gerontology
Total funding: $249,377
Start Year: 2009
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
Randomised controlled trial of yoga for improving sleep and quality of life in an elderly
populationRandomised controlled trial of yoga for improving sleep and quality of life in an elderly population
Lay Description (from application):
Insomnia is very common in the elderly and is associated with increased morbidity and reduced quality of life.
Yoga is purported to assist with sleep and stress management but there is little rigorous research to confirm this
and no research to determine if yoga can be adapted to an elderly population in Australia. This study aims to
rigourously examine the effectiveness of yoga as an intervention for geriatric insomnia and to determine the
ability of yoga to enhance quality of life.
Research achievements (from final report):
This study aimed to determine if an integrated yoga intervention improves subjective and objective sleep
measures in elderly people with insomnia. The study demonstrated that it is indeed possible to design a double
blind controlled trial involving a yoga intervention however, due to an inability to recruit sufficent numbers,
the research question was not able to be answered definitively.
Expected future outcomes:
N/A
Name of contact:
Prof Marc Cohen
Email/Phone no. of contact:
marc.cohen@rmit.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 616621
Start Year: 2010
CIA Name: A/Pr Paul Wright
End Year: 2013
Admin Inst: RMIT University
Grant Type: NHMRC Project Grants
Main RFCD: Nanotoxicology, Health and Safety
Total funding: $586,816
Title of research award:
Immunotoxic effects of engineered nanomaterials used in the Australian workplaceImmunotoxic effects of
engineered nanomaterials used in the Australian workplace
Lay Description (from application):
Certain engineered nanomaterials are more toxic than their bulk material forms. We urgently need the ability to
re-engineer these nanomaterials to reduce their toxicity and potential health risks, but lack the necessary
knowledge. This project directly addresses the NHMRC Strategic Initiative on Nanotechnology and Health, by
providing essential information for designing safer nanomaterials from systemically studying the immune
effects of metal oxide nanoparticles used in Australian industry.
Research achievements (from final report):
This NHMRC project grant directly addressed the NHMRC's Strategic Plan Initiative of "Nanotechnology and
Health". It has provided essential information about the effects on the immune system of exposure to
nanomaterials, including the nanoparticles used in sunscreens.
Our studies of cultured human immune and skin cells show that, overall, sunscreen nanoparticles are as well
tolerated as the conventional organic chemical sunscreens. Also, human cells co-exposed to both sunscreen
nanoparticles (zinc oxide or rutile titanium dioxide) and ultraviolet light produced less free radicals than with
UV exposure alone. This project has provided detailed experimental proof that using these nanoparticles in
sunscreens is safe. It has positively impacted on public health practice by confirming that excessive UV light is
a well-known and greater risk for skin damage and cancer compared to a perceived risk from using
nanosunscreen.
A new imaging technique was also developed using the Australian Synchrotron to view intact nanoparticles
inside human immune and skin cells. It is the first high-throughput method of this type and has also allowed us
to see, for the first time, sunscreen zinc oxide nanoparticles dissolving inside human immune cells.
The project has also enabled the joint RMIT-Monash University nanosafety research group to be a major
member of the Australian Consortium that recently participated in the global OECD nanosafety testing
program for engineered nanomaterials. This OECD involvement has ensured a greater impact of this research
on global public health policy by disseminating this project's findings to a wider national and international
audience.
Expected future outcomes:
The research findings from this project will help to produce "value-added" nanomaterials that are "safer-bydesign", specifically the design of safer and more effective sunscreens, and computer modelling of nanoparticle
behaviour. The new synchrotron imaging technique will aid in the development of cell analysis with higher
capacity than is presently possible.
Name of contact:
Associate Professor Paul Wright
Email/Phone no. of contact:
paul.wright@rmit.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 446201
Start Year: 2007
CIA Name: Prof Annemarie Hennessy
End Year: 2012
Admin Inst: Royal Prince Alfred Hospital
Grant Type: NHMRC Enabling Grants
Main RFCD: Medical Physiology not elsewhere classified
Total funding: $632,700
Title of research award:
The National NHMRC Baboon ColonyThe National NHMRC Baboon Colony
Lay Description (from application):
The National NH&MRC Baboon colony provides access to large non-human primates to support Australia’s
research efforts in diverse scientific areas around the country. These include diabetes research (kidney
involvement and prevention of kidney damage, nerve damage and eye damage); treatment options inlcuding
gene therapy of blood/bone-marrow cancers; understandng pregnancy changes in blood pressure and the causes
of hypertension (high blood pressure) in pregnancy; identification of new techniques for analyis of brain
function; the effects of aging on liver function especially with regards to drug metabolism; new therapies for
transplantation which would allow more rational and lower/safer drug use for transplant patients; breaking
down the barriers to animal-to-human transplantation through assessment of safety and development of new
techniques; behavioural aspects of fertility management; vaccine development; development of oral
vaccination; the nature of wound healing.
There is diverse and wide access to the National NHMRC Baboon colony from research interests around
Australia. The use of the animals is at all times approved by the Animal welfare Committee governing the
colony, as well as that which governs the researchers involved. All approved projects have been given access to
the animals required. The need for non-human primate use as opposed to other animals or other techniques not
involving animals is justified to the relvant committees before any project proceeds. The use of the animals
therefore adds a dimension to Australian research due to animal similarity to humans physiology or size
comparisons.
Contributions made by the colony in the last 20 years are listed in the attached references, but understanding
physiology at a depth not possible with other animals has changed our thinking about the human condition as a
result of primate -based research.
Research achievements (from final report):
The provision of a colony of healthy, higher-order, non-human primates to the Australian biomedical research
community has allowed highly relevant research to be carried out in multiple national health priority areas.
Research into cardiovascular disease, diabetes, transplantation, pregnancy complications and other areas has
been facilitated by the provision of NHMRC funding. Research groups from 18 different institutions have been
supported by access to the NBC.
Expected future outcomes:
The ANBC will continue to meet its objectives of providing a healthy colony of non-human primates for
scientifically and ethically justified biomedical research in Australia. The maintenance of the highest standard
of animal welfare is a key priority.
Name of contact:
The Director
Email/Phone no. of contact:
RPAH.NBC@sswahs.nsw.gov.au
NHMRC Research Achievements - SUMMARY
Grant ID: 343603
CIA Name: A/Pr Scott Wilson
Admin Inst: Sir Charles Gairdner Hospital
Main RFCD: Quantitative Genetics
Total funding: $403,625
Start Year: 2005
End Year: 2007
Grant Type: NHMRC Project Grants
Title of research award:
Genetic regulation of hip geometry, structure and fractureGenetic regulation of hip geometry, structure and
fracture
Lay Description (from application):
Osteoporotic hip fracture is common in the elderly and a major cause of hospitalization. Hip fracture may lead
to surgery, chronic reduced mobility, loss of function, institutionalization or death. The term osteoporosis
covers a heterogeneous syndrome including juvenile, secondary (e.g. corticosteroid induced) and
postmenopausal osteoporosis. This later broad grouping shows evidence of a strong familial association.
Previous work has shown that a family history of fracture increases the risk of fracture by more than four fold.
Furthermore, studies in twins have persistently shown that phenotypes such as bone mineral density (BMD),
broadband ultrasound attenuation of bone and hip structural indices are strongly inherited. This confirms a
genetic basis for the disease in some individuals. Community health in general has improved substantially in
Australia in the past four decades and this has resulted in increased longevity. In contrast, the incidence of hip
fracture and the resulting drain on public health funding continues to increase rapidly. Presently the cost of
osteoporosis in Australia is $7.5 billion per annum. Hip fracture accounts for the majority of these costs.
Instituting effective prevention strategies is essential. This project aims to contribute to one of Australia's
National Research Pritoities by improving understanding about the way in which inherited aspects of hip
geometry and structure contribute to the hip fracture susceptibility. We have successfully completed genome
screen projects studying genetic linkage in the families to localize genes regulating BMD in the past.
However, BMD is only one of a number of relevant phenotypes. In relation to hip fracture, geometry and
structure are thought to be particularly important. In this project we will make use of existing resources to
advance studies of both genetic linkage and association to examine fundamental issues related to hip facture.
Research achievements (from final report):
Osteoporotic hip fracture is common in the elderly and is a major cause of morbidity and mortality, the goal of
this project was to find genes that control hip structure, particularly those which are relevant to hip fracture.
The study used existing radiographs and dual x-ray absorptiometry (DXA) scans on a large cohort of women
and derived important new phenotypes on hip structure and geometry from these resources. That phenotype
data was then used in analyses with existing genetic data for these study subjects to identifying genes with a
potential role in the regulation of hip geometry and structure. We identified 13 discrete genomic regions that
showed genetic linkage to hip structure and geometry phenotypes. Furthermore, we identified 23 individual
genes with replicated evidence of statistically significant association with hip structure traits. These results
assist in improving knowledge and understanding of the genetic control of hip structure. The long-term goal of
the research program is to develop intervention strategies to reduce hip fracture incidence.
Expected future outcomes:
This data will enable targeted validation studies of the mechanisms involved in the genetic regulation of hip
structure and geometry. Although further replication and molecular biology studies are necessary to fully
validate the findings, some of the genes identified may be useful in the development of diagnositic and
therapeutic approaches for osteoporosis and osteopeania.
Name of contact:
Lynell Belardo
Email/Phone no. of contact:
Lynell.Belardo@health.wa.gov.au
NHMRC Research Achievements - SUMMARY
Grant ID: 207701
CIA Name: Prof Nicola (Nick) Fazzalari
Admin Inst: University of Adelaide
Main RFCD: Orthopaedics
Total funding: $317,640
Start Year: 2002
End Year: 2004
Grant Type: NHMRC Project Grants
Title of research award:
Molecular determinants of bone remodelling in the bone microenvironmentMolecular determinants of bone
remodelling in the bone microenvironment
Lay Description (from application):
There is little information regarding the expression of specific molecules in human bone tissue or their role in
skeletal disease. The process of bone remodelling is fundamental for the maintenance of skeletal integrity. Our
understanding of the molecular signalling involved in activating bone remodelling is principally derived from
tissue culture and animal experiments. We will study human cancellous bone samples donated by patients
undergoing surgery, and with the consent of the next-of-kin, taken at autopsy. These molecular and
histomorphometric studies will determine whether the understanding derived from tissue culture and animal
experiments is consistent with associations demonstrable in the human cancellous bone microenvironment. The
elucidation of the molecular signalling in the human bone microenvironment is essential for the effective
diagnosis and treatment of bone disease. Recently reported studies have shown very persuasively that fatigue
microdamage accumulates in the skeleton and is targeted for repair by remodelling. Our preliminary data
shows that microcrack length is positively correlated with IL-11 mRNA gene expression. We will further
investigate mRNA gene expression of a number of cytokines involved in bone cell signalling and their
association with the level of microdamage in the bone. Using a animal model of controlled bone microdamage
induction we will seek to determine the bone remodelling causal relationship between microdamage and
cytokine signalling. Furthermore, the cellular and molecular mechanisms that lead to trabecular structures are
not well understood. These studies will provide new insight into the processes that determine trabecular
structures. This project will investigate these mechanisms and increase our understanding of bone cell function,
essential for diagnosis and design of rational treatment for bone diseases.
Research achievements (from final report):
In this project, we have investigated the expression of key regulatory molecules of bone renewal in the
microenvironment of trabecular bone samples from patients who have suffered osteoporotic fragility fractures
and osteoarthritis. We have combined investigation of gene expression in human bone with measurement of
tissue morphology (histomorphometry), to investigate links between molecules that participate in bone
renewal. Bone samples were taken from patients undergoing hip replacement for a fragility fracture of the
femur and total hip replacement for osteoarthritis. We have found that the expression of a number of key genes
that control bone renewal, RANK and IL-6 mRNA and RANKL/OPG mRNA ratio, was significantly elevated
in the osteoporotic fracture group compared to an age-matched control group. These data suggest a relative
increase in the expression of the molecular promoters of osteoclast formation (cells that remove bone) and
activity in osteoporotic fragility fracture bone, which may lead to the imbalance between bone formation and
removal associated with fragility fracture. When the same bone samples used for molecular analysis were
examined by histomorphometry, bone formation parameters were significantly reduced in the fracture patients
compared to controls. These data are important because they are among the first to draw attention to a
reduction in bone formation, rather than increased bone removal, in association with osteoporotic fragility
fractures. In additional work, we have performed microarray experiments, comparing gene expression in
osteoporosis and osteoarthritis bone samples. A number of different classes of genes have been identified as
being up-regulated in osteoporosis compared to osteoarthritis, which is consistent with the reduced bone mass
seen in osteoporosis compared to osteoarthritis. This project grant increased our understanding of the
mechanisms of bone renewal and potentially identified new tragets for novel drug development.
Expected future outcomes:
NHMRC Research Achievements - SUMMARY
Our studies have shown that the disregulation of bone cell signals and their relationship to bone tissue
properties is a potential determinant of fragility fracture risk. The elucidation of the mechanism of bone
renewal identifies potential new tragets for novel drug development.
Name of contact:
Nick Fazzalari
Email/Phone no. of contact:
nick.fazzalari@imvs.sa.gov.au
NHMRC Research Achievements - SUMMARY
Grant ID: 207792
CIA Name: Prof Robert Vink
Admin Inst: University of Adelaide
Main RFCD: Central Nervous System
Total funding: $241,650
Start Year: 2002
End Year: 2004
Grant Type: NHMRC Project Grants
Title of research award:
Characterisation of Substance P antagonists as a novel therapeutic intervention for use in traumatic brain
injuryCharacterisation of Substance P antagonists as a novel therapeutic intervention for use in traumatic brain
injury
Lay Description (from application):
Traumatic brain injury (TBI) is responsible for more deaths in Australians under 45 years of age than any other
cause. The economic and social cost of head injury to the community is enormous with billions of dollars
spent each year on the management and rehabilitation of trauma patients. Despite the enormity of this public
health problem, no effective treatment currently exists. A number of studies have demonstrated that much of
the morbidity following TBI is associated with the development of a secondary injury process that occurs
between hours to days after the insult. This delayed progression of injury suggests that appropriate
pharmacologic intervention can prevent, or at least attenuate, this secondary injury process with a resultant
improvement in outcome. Over the past 15 years, a number of groups, including ours, have been investigating
the secondary mechanisms associated with the development of functional deficits after TBI. Our previous
studies have demonstrated that decline in brain free magnesium is associated with functional deficits after
experimental brain injury, and that magnesium administration after injury can improve outcome. Magnesium
is now on clinical trial as a pharmacologic intervention. Recent studies have suggested that magnesium decline
facilitates neurogenic inflammation, which has been associated with oedema formation, oxidative damage and
cell death. Although a number of neuropeptides have been implicated in this process, it is thought that
substance P release is closely associated with these pathophysiological processes. Therefore, inhibiting
neuropeptide release, or inhibiting substance P binding, may offer a novel therapeutic approach for the
attenuation of oedema and development of neurologic deficits after TBI. This proposal will use a combined
biochemical, pharmacologic and behavioural approach to characterise the role of neuropeptides in brain
trauma, and attempt to develop a novel therapy for use in clinical trauma.
Research achievements (from final report):
We established that brain swelling (oedema) following traumatic brain injury followed a biphasic pattern, with
an early peak in brain water content occurring within 6 hours, followed by a second peak in brain water content
at three days after trauma that persisted for approximately 1-2 weeks. The early peak was associated with
increased vascular permeability, whereas the later phase was cellular oedema. The early oedema formation was
initiated by neuropeptide release, and in particular substance P, which increased blood brain barrier
permeability and facilitated the development of the early oedema. By inhibiting substance P release or binding,
we were able to prevent early onset oedema formation, and this subsequently led to an attenuation of the later
oedema. We concluded that the early oedema facilitated the subsequent cellular oedema. Administration of a
substance P antagonist not only attenuated oedema formation, but also improved motor and cognitive
outcomes. Moreover, the drug could be administered as late as 12 hours after the traumatic event and still result
in a significant reduction in brain swelling and an improvement in outcome. A more specific substance P
antagonist with no known side-effects was then donated by Roche pharmaceuticals and we were able to
establish that this compound was equally effective at preventing post-traumatic oedema formation and
improving functional outcome. This compound was subsequently patented and is expected to be entered into
clinical trials in 2006/2007. If successful, this drug has the potential to reduce mortality and morbidity after
traumatic brain injury, and significantly reduce the time victims of brain injury would spend in hospital.
Expected future outcomes:
The compound that was developed in this study will be entered into clinical trials in late 2006/early 2007. If
successful, it would revolutionise the management of brain swelling following traumatic brain injury.
NHMRC Research Achievements - SUMMARY
Name of contact:
Professor Robert Vink
Email/Phone no. of contact:
Robert.Vink@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 250301
CIA Name: Prof Nicola (Nick) Fazzalari
Admin Inst: University of Adelaide
Main RFCD: Orthopaedics
Total funding: $423,625
Start Year: 2003
End Year: 2005
Grant Type: NHMRC Project Grants
Title of research award:
Interrelationships between the disc and bone of lumbar spinal segmentsInterrelationships between the disc and
bone of lumbar spinal segments
Lay Description (from application):
The cause of back pain due to osteoarthritis, osteoporotic vertebral crush fracture, and ageing is poorly
understood. Vertebral deformity, intervertebral disc disorganisation, and change to vertebral bone structure are
features associated with degeneration of the spine and with back pain. Degenerative disc disease is one of the
major causes of back symptoms and is believed to be associated with degeneration of the spine. Spinal
degeneration includes disc degeneration, facet joint osteoarthritis, compromised vertebral body bone quality,
muscle and ligament alterations. It is assumed that these changes result in increased or abnormal spine motion
and modified load distribution across the spinal joint. It has been found that with age, there is increased
disorganisation of the intervertebral disc and decreased quality of vertebral cancellous bone. However, bones
with the same density within the range of normal subjects, can show selective loss of bone structure and
reduced load-bearing capacities of these vertebrae. An important concept here is that even for a given bone
mass, fracture risk increases with age, supporting the view that there is a component of bone fragility that is
independent of mass. Increased bone fragility may be associated with compromised cancellous bone structure.
While the relationship between disc degeneration and changes in vertebral bone is commonly invoked, the
mechanisms of this relationship have largely been overlooked, with age changes given more attention.
However, it may be that intervertebral disc disorganisation modulates age-related bone changes within the
spine. Disc degeneration may influence trabecular bone responses before changes with age put the patient at
risk of vertebral crush fracture. We propose that the mature disc cannot effectively regenerate after damage,
and thus responses to disc damage will be more readily observed in vertebral bone architecture than in the disc.
Research achievements (from final report):
We have developed and implemented a novel MRI protocol to measure the water content of the intervertebral
discs in the human spine. This protocol is breaking new ground in that it provides a new clinical tool to
measure the water content of the intervertebral disc of patients with back pain. We have been able to show that
the MRI scans are reliable and reprobucible. Until the development of this technique, assessing the amount of
water in the intervertebral disc has been based on the subjective interpretation of an MRI image by a
radiologist. There are few studies of this nature that have been reported and a patent application is pending. , In
addition, this study has provided a novel perspective of the bone in the spine. The thickness of the bone wall
that surrounds the spongy bone structure in the vertebral body was thicker in the front of the vertebra than the
back of the vertebra, suggesting that the bone wall in the front of the vertebra has to support a greater load than
the back wall of the vertebra. Combined with the data we have on the deformation of the vertebral body bone
wall under load and how the load is transmitted through the spongy bone in the vertebral body we have a
unique insight into vertebral body mechanics. This places us at the forefront of understanding the mechanism
of vertebral body fracture where the patient has fragile bones. The study has enabled us to better understand the
relationship between the intervertebal disc and the vertebral body bone. These unique data from the human
spine have not been previously reported and hold significant potential to understand bone quality factors that
ultimately determine bone strength and what factors should be the target of treatment.
Expected future outcomes:
This was a pioneering study using a multidisciplinary approach and our unique experience to elucidate the
mechanisms of spinal degeneration. The MRI protocol to measure the water content of the disc will provide a
new clinical tool to identify the presence of disc degeneration, monitor progression of disc degeneration and
monitor the efficacy of treatment of disc degeneration in patients.
NHMRC Research Achievements - SUMMARY
Name of contact:
Nick Fazzalari
Email/Phone no. of contact:
nick.fazzalari@imvs.sa.gov.au
NHMRC Research Achievements - SUMMARY
Grant ID: 250344
CIA Name: Prof David Findlay
Admin Inst: University of Adelaide
Main RFCD: Orthopaedics
Total funding: $368,000
Start Year: 2003
End Year: 2005
Grant Type: NHMRC Project Grants
Title of research award:
Mechanisms of Periprosthetic Bone LossMechanisms of Periprosthetic Bone Loss
Lay Description (from application):
We will seek to address an important clinical problem in orthpaedics, namely the bone loss that commonly
occurs around joint replacement prostheses. Termed peri-prosthetic osteolysis (PO), this bone loss can result in
the loosening and ultimate failure and need for revision of the artificial joint components. PO is thought to be
caused by the body's reaction to wear particles generated from the articulating surface of the prosthesis.
However, it has not previously been possible to accurately explore the relationship between prothesis wear and
PO, or the progression of PO, because of a lack of techniques to image and measure the volume of PO around
metal prosthesis components. We have developed a means to accurately and reproducibly measure the volume
of bone loss, using CT, and will do so longitudinally in joint replacement patients to obtain the first information
about the progression of PO. New computer based methods will be used concurrently to relate prosthesis wear
and migration parameters to PO. Patients who come to surgery for replacement of failed prostheses will be
investigated further by analysis of the tissues involved in the bone loss around prostheses. Basic science
experiments will seek to understand the underlying causes of PO and the findings will be important in
interpreting the clinical results. An animal model will be used to seek approaches to inhibiting the pathological
response to wear particles. The significance of these studies is that they will lead to improved outcomes for
joint replacement patients, increasing the interval to revision surgery, which is both extremely costly and brings
an attendant morbidity and mortality.
Research achievements (from final report):
Peri-prosthetic osteolysis often limits the lifespan of total hip replacement implants. Therefore, the aim of this
project was to investigate peri-prosthetic bone loss, firstly by developing new imaging modalities and secondly
by identifying the molecular mechanisms responsible for this process. We made great progress towards these
goals, measuring in the same patient implant wear and migration and, for the first time, the progression of
osteolysis. In patients who required revision surgery, we analysed tissue taken from defined sites adjacent to
osteolytic lesions and found important relationships between particle accumulation in the tissues, the cell types
present, and the molecular species that are potentially causally involved in the pathological bone loss. These
cytokines, such as TNF and RANK ligand, were found in separate experiments to potentiate osteoclast
formation and activity. This work has therefore laid a strong basis for a new means of monitoring hip
replacement patients and for understanding (and therfore potentially treating) the cell and molecular basis for
the bone loss that often occurs around prostheses.
Expected future outcomes:
As stated, this work has therefore laid a strong basis for a new means of monitoring hip replacement patients,
which has been anabled by our development of a means to accurately quantitate osteolysis around medium to
long term hip replacements. The basic science part of the work may lead to new treatments for this bone loss.
Name of contact:
David Findlay
Email/Phone no. of contact:
david.findlay@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 274307
CIA Name: Dr John Semmler
Admin Inst: University of Adelaide
Main RFCD: Motor Control
Total funding: $198,500
Start Year: 2004
End Year: 2006
Grant Type: NHMRC Project Grants
Title of research award:
Motor unit synchronisation and neuromuscular performanceMotor unit synchronisation and neuromuscular
performance
Lay Description (from application):
The fine control of force is important for many everyday tasks such as writing, grasping objects between index
finger and thumb, and fastening buttons. Factors that influence the ability to control force include the
coordinated activation of groups of muscle fibres called single motor units. This proposal focuses on the
concept that the coordinated activation of motor units is influenced by muscle activity and can impair the
ability to produce finely controlled muscle contractions. The goal of these studies is to explore the boudary
conditions of the adaptive nature of the nervous system to examine how coordinated motor unit activity
influences these aspects of neuromuscular performance. The outcomes of these experiments will identify if
altering muscle activity influences the control of movement by altering single motor unit activity. These
results will have direct application to the interpretation of abnormal movement control and tremor that is
observed in certain neurological diseases such as Parkinson's disease. Furthermore, new information will be
gained on the adaptability of the motor system and its role in the execution of fine motor tasks that may aid in
the development of rehabilitation strategies following stroke or spinal cord injury.
Research achievements (from final report):
The purpose of these studies were to determine whether changes in muscle strength influenced the control of
force by the nervous system. Experimental measures were performed at the level of the single motor unit,
which is the smallest element of neuromuscular control. We found that damaging the muscle with repetitive
lengthening contractions altered the correlated activity of human motor units and influenced the fine control of
force. However, a short period of strength training did not influence the neural control of force despite
significant increases in muscle strength. These studies demonstrate that alterations in strength of the muscle do
not appear to influence the correlated discharge of action potentials and do not impair fine motor control.
Rather, we suggest that correlated motor unit activity is an effective strategy to promote skilled and
coordinated movements, but could impair the ability to perform steady contractions under some circumstances.
These results will have direct application to the interpretation of abnormal correlated motor unit activity and
pathological tremor that is observed in certain neurological conditions such as Parkinson's disease.
Expected future outcomes:
The future direction of this work is twofold. First, we plan to explore the neural mechanisms that impair motor
performance following exercise-induced muscle damage. Second, we will examine the neural adjustments in
the central nervous system following skilled motor performance. These studies will have implications for
neuromuscular function and rehabilitation in athletes and patients.
Name of contact:
John Semmler
Email/Phone no. of contact:
john.semmler@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 298900
CIA Name: A/Pr Allison Cowin
Admin Inst: University of Adelaide
Main RFCD: Dermatology
Total funding: $472,750
Start Year: 2004
End Year: 2006
Grant Type: NHMRC Project Grants
Title of research award:
Function of the Flightless protein in wound repair and scar formation in skinFunction of the Flightless protein
in wound repair and scar formation in skin
Lay Description (from application):
Understanding the factors that control T cell responses has been a major focus of immunology. Despite this
effort the factors that control T cell development, homeostasis and function are still only incompletely
understood. Accordingly we have been studying the TNF-family cytokine BAFF (B cell activation factor of the
TNF-family) in relation to T cell behaviour and function. Though BAFF was first described as being critical for
B cell development and maturation, a number of lines of evidence indicate that BAFF may be important in T
cell biology. Current studies suggest that BAFF exerts a pro-inflammatory effect upon T cell responses.
Surprisingly then, when we examined the role of BAFF upon T cell function in vivo in the context of the alloimmune response, we found that ~60% of BAFF transgenic mice failed to reject a fully-mismatched allograft.
Intriguingly, BAFF transgenic mice exhibited an increased number of CD4+ CD25+ Foxp3+ cells in the
periphery and in vivo depletion of these CD25+ cells restored the ability of BAFF transgenic mice to reject an
allograft. We hypothesize that BAFF plays a potentially powerful anti-inflammatory role in regulating certain
T cell dependent immune responses. Our data suggests that BAFF can modulate T cell function by effecting T
cell regulation.
Research achievements (from final report):
Our studies, investigating the function of the actin cytoskeleton in wound repair have revealed the potentially
important role of Flightless I, an actin-remodelling protein, in wound healing and scar formation. Using in vitro
and in vivo approaches our studies have revealed that FliI plays a key role in promoting cellular migration and
proliferation. We have further identified that changing FliI gene expression affects wound repair. Using mice
with different levels of FliI expression we found that FliI deficiency significantly improves healing. We have
now commenced the development of a novel antibody-based treatment aimed at reducing FliI expression in
wounds. Crucially, our in vitro and in vivo studies reveal that when this antibody is applied topically to wounds
in vivo we see improvements in wound healing. The benefit of a new therapy for improving wound repair and
decreasing scar formation is potentially of great importance particularly for children suffering from burn
injuries.
Expected future outcomes:
Future outcomes include the development of new FliI-based therapies for treating wounds and reducing scar
formation. We will also continue studies aimed at understanding the mechanisms of FliI action in wound
healing. We hope to translate these findings into new clinical applications aimed at treating burn injuries which
can lead to devastating disabilities in children and adults.
Name of contact:
Allison Cowin
Email/Phone no. of contact:
allison.cowin@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 298933
CIA Name: Prof Howard Morris
Admin Inst: University of Adelaide
Main RFCD: Orthopaedics
Total funding: $399,750
Start Year: 2004
End Year: 2006
Grant Type: NHMRC Project Grants
Title of research award:
Vitamin D Depletion and Femoral Bone LossVitamin D Depletion and Femoral Bone Loss
Lay Description (from application):
An understanding of the way cells control their complex internal circuitry is relevant to diseases like cancer
and leukemia. The main focus of this project is a cellular regulator we identified several years ago called
BORIS. Normally dormant in all cells outside the male reproductive organs, BORIS is reactivated in many
cancers. We will study the network of factors perturbed when BORIS becomes inappropriately active in cancer
cells. Ultimately this project may lead to new treatments for cancer.
Research achievements (from final report):
A robust rodent model of vitamin D depletion has been developed. These animals have vitamin D levels that
are considered low but are the maximum achieved by some 50% or more of the community. Our studies
demonstrated that these rodents developed osteoporosis at early adulthood, that is just one quarter through their
life span, which was surprising. It was proposed that osteoporosis would not develop until they were older.
Similar biochemical markers were measured in the rodent model as have been measured in humans who have
low vitamin D levels. A very similar relationship was found suggesting that the findings with this model are
likely to be useful for estimating human vitamin D requirements. A minimum level of vitamin D for optimal
bone striucture was identified. As well the study identified the optimal form of vitamin D for skeletal health.
The loss of bone that occurred with low vitamin D levels was due to high bone resorption due to high levels of
bone resorbing cells. Evidence for the molecular mechanism of the increased number of bone resorbing cells
was obtained. Evidence has been obtained that a lower level of vitamin D is required to maintain optimal
skeletal health as dietary calcium levels increase.
Expected future outcomes:
The effects of age and dietary calcium intake on the level of vitamin D required for optimal skeletal health and
bone strength will be elucidated. It is expected that as we age we require higher levels of vitamin D to maintain
our health. Currently there is no understanding of the basis for such increased requirement and these studies
will provide the first indications.
Name of contact:
Professor Howard Morris
Email/Phone no. of contact:
howard.morris@imvs.sa.gov.au
NHMRC Research Achievements - SUMMARY
Grant ID: 299031
CIA Name: Dr Gerald Atkins
Admin Inst: University of Adelaide
Main RFCD: Orthopaedics
Total funding: $436,450
Start Year: 2004
End Year: 2006
Grant Type: NHMRC Project Grants
Title of research award:
Relationships Between Human Osteoblasts and Haemopoietic Cells in Bone RemodellingRelationships
Between Human Osteoblasts and Haemopoietic Cells in Bone Remodelling
Lay Description (from application):
Bone diseases, such as osteoporosis and osteoarthritis, currently afflict more than 4 million Australians. These
diseases are characterised by abnormal bone remodelling, which can result in a net loss of bone (for example,
in osteoporosis) or abnormal bone structure (for example, in osteoarthritis). We are seeking to better
understand the factors that regulate bone remodelling, and particularly the cells involved in this process.
Physiological bone remodelling results from the intimate collaboration between osteoblasts and osteoclasts.
Osteoblasts stimulate the formation of osteoclasts and also produce new bone at resporption sites. However,
the way that the same type of cell can perform both these tasks, is not clear. Our studies are designed to
increase our understanding of the development of human osteoblasts and of the factors that cause them to be
sequentially pro-osteoclastic and then pro-osteogenic. We believe that an important factor in this process is
vitamin D and we will test the hypothesis that this molecule is produced in bone and acts locally to regulate
bone turnover.
Research achievements (from final report):
The aims of this proposal were: 1.
To further define the link between the
osteoblast differentiation state and the formation of osteoclasts in response to various factors that act on the
skeleton;, 2.
To further characterise the signals
between, and the influences of, haemopoietic cells and osteoblasts during both osteoclastogenesis and
osteogenesis;, 3.
To define the role of
1,25(OH)2vitamin D3 metabolism in human bone cell biology., This has been a highly successful and
productive period of research, resulting to date in 11 publications including two book chapters. At least 6
further publications describing work encompassed in this project are in preparation. We have succeeded in
obtaining significant new insight into human osteoblast biology with respect to their production of osteoclast
activating factors, their response to osteoclast derived factors, and the way in which they differentiate into
mineral producing cells and further, into mature osteocytes. We have established that the skeleton is an
intracrine organ for vitamin D metabolism, effectively describing a paradigm shift in this field. This has
important implications for the interpretation of the diagnostic indicator of vitamin D status, namely, the serum
25-hydroxyvitamin D level. We have characterised a number of pathways whereby osteoblast differentiation is
modulated by proinflammatory signals deriving from both haemopoietic cells and from osteoblasts themselves,
which is likely to be important in bone repair and in diseases of bone inflammation, such as rheumatoid
arthritis and osteoporosis. We have also established an effective model, with which to examine the mechanism
of action of anabolic therapeutics for the treatment of osteoporosis. Our results have direct implications for the
treatment of a number of bone degenerative diseases.
Expected future outcomes:
This project has formed the basis of two further major projects, examining the role in bone of the inflammtory
cytokine TWEAK, and the effect on bone cells of wear particles derived from orthopaedic prostheses. We have
also established important collaborations with international companies to investigate the modes of action of
skeletal therapeutics on human bone cells in vitro.
Name of contact:
Dr. Gerald Atkins
Email/Phone no. of contact:
NHMRC Research Achievements - SUMMARY
gerald.atkins@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 399168
CIA Name: Prof David Findlay
Admin Inst: University of Adelaide
Main RFCD: Orthopaedics
Total funding: $515,917
Start Year: 2006
End Year: 2008
Grant Type: NHMRC Project Grants
Title of research award:
Impaired bone remodelling leads to failure of orthopaedic prosthesesImpaired bone remodelling leads to failure
of orthopaedic prostheses
Lay Description (from application):
The failure of bone prostheses is becoming a major health problem. More than 26,000 hip, and an equal
number of knee, replacements were performed in Australia in 2002 with the number increasing between 5%10% each year for the previous 10 years. Disturbingly, the incidence of revision hip surgery in Australia is now
more than 15%, meaning that, despite the impressive success of joint replacement surgery, a significant number
of arthroplasties fail. It is becoming more common for young, active individuals to receive joint replacement
surgery to improve their quality of life. This, combined with increasing life expectancy, and the known higher
rate of failure of joint replacements in younger patients, means that the morbidity of a failed replacement, and
the mobidity and associated mortality of revision surgery, will become an increasingly important health issue,
with a major impact upon health budgets. The overwhelming majority of hip and knee prostheses have metal or
ceramic on polyethylene bearing surfaces. It is now apparent that most implants fail due to bone loss around
them leading to loosening, and evidence is accumulating that polyethylene wear particles are a major
contributing factor to this process. It is therefore vital that we obtain better understanding of the causes of
implant failure in order to extend the life of these implants and this project is designed to do so.
Research achievements (from final report):
The aim of this project was to understand the reasons for the eventual loss of bone that is observed around
artificial joints. We found previously that polyethylene (PE) particles generated in the joint by wear of the
articulating surface of the prostheses were strongly related to the extent and rate of bone loss. In this project,
we have shown that where PE particles accumulate in the joint tissues, there is an accompanying accumulation
of giant cells, which engulf the particles and also molecules that are involved in the physiological resorption of
bone. These molecules include RANK, RANKL, OSCAR, TWEAK and TNF. In further investigating the
action of these molecules on bone cells, we have found that TWEAK reduces the ability of osteoblasts to make
bone. To examine more directly the mechanism, by which PE particles interact wirth osteoblasts and
osteoclasts, we have obtained PE particles similar to those produced as prostheses begin to wear. We have
devised a novel method of exposing cells to these particles by including them with cells in a gel material. We
have found that osteoblasts behave very differently in the presence of PE particles. Specifically, they produce
less of the substances required to make bone and more of the molecules that promote osteoclast formation. In
addition to this, we have found that PE particles can directly increase the production of osteoclasts from their
precursor cells.
Expected future outcomes:
Our findings show a direct role for PE particles in the bone loss around articulating orthopaedic implants and
draw attention to the need for new bearing materials with better wear characteristics. They also provide clues
for preventing this bone loss, while at the same time encouraging continued bone formation around implants.
?????
Name of contact:
David Findlay
Email/Phone no. of contact:
david.findlay@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 399305
CIA Name: Prof Nicola (Nick) Fazzalari
Admin Inst: University of Adelaide
Main RFCD: Orthopaedics
Total funding: $447,027
Start Year: 2006
End Year: 2008
Grant Type: NHMRC Project Grants
Title of research award:
Intrinsic bone qualities in fragility fracture patients: mass, microarchitecture, mineralization and damage
accumulationIntrinsic bone qualities in fragility fracture patients: mass, microarchitecture, mineralization and
damage accumulation
Lay Description (from application):
Osteoporosis drug therapies have been associated with a significant reduction in fragility fracture. Patients
receiving osteoporosis drugs, which have different effects on BMD, may have similar reductions in fractures.
Furthermore, patients with fragility fractures may have abnormalities in bone structural and material properties.
Changes to the process of bone renewal, due to drug therapy, may explain why fracture risk decreases where no
detectable change to the structure of bone has been detected. It has also been shown that when bone renewal is
suppressed microdamage accumulates in bone tissue, leading to reduced bone toughness. The toughness of
bone is of primary importance in relation to fragility fractures, and it has been shown that the fatigue strength
and fracture toughness (work to fracture) reduce considerably with age. This proposed study would seek to
elucidate the role of bone tissue-level properties in determining bone quality for human subjects: patients with
fragility hip fractures on no osteoporosis drugs therapy, hip fracture patients on osteoporosis drugs therapies,
and normal age- and sex-matched individuals. Our laboratory has extensive experience in the analysis of the
structure of human bone tissue. Recently, we have developed novel and unique techniques to assess bone
quality, using micro-CT, backscatter SEM imaging, confocal microscopy and immunohistochemistry. This
multifaceted study will identify at the bone tissue-level the structural mechanisms (micro-architecture,
mineralisation, and microscopic cracking) that are indicative of the efficacy of fragility fracture drugs. Better
understanding of the mechanisms by which bones are less likely to fracture will enable better targeting of
osteoporosis drug therapy to individuals at risk of fragility fracture.
Research achievements (from final report):
Fragility fracture risk is strongly dependent upon skeletal strength. Low bone mass is not the sole predictor of
loss of bone strength. Bone strength is determined by a number of inter-related structural and material
components, collectively constituting bone quality. We have undertaken complementary investigations of bone
structure (how bone is arranged in 3D space), bone mineralisation (how soft or brittle the bone is), and bone
microdamage accumulation (how many microscopic cracks are present in the bone) on bone specimens from
the femur from patients with fragility hip fractures that were not/were receiving osteoporosis drug therapy and
skeletally normal individuals (non-fracture controls). Measurements of trabecular bone volume (3D bone mass)
and bone microarchitecture do not discriminate hip fracture patients from controls. However, bone from hip
fracture patients is less mineralised and contains more unrepaired microdamage (damage is repaired/removed
by bone turnover) compared to control individuals. Hip fracture patients that were receiving osteoporosis drug
therapies prior to fracture, show a different bone mineralisation profile compared to the fracture patients not on
therapy and controls. Our data demonstrate that the effect on bone of osteoporosis drug therapies, and hence
reduction of secondary fragility fracture, may differ on an individual patient basis. Our finding of altered bone
mineralisation profiles for hip fracture patients that were not/were receiving osteoporosis drug therapies and
non-fracture controls implicates the involvement of bone turnover in determining bone material quality, and
hence bone strength. This project has delivered novel material property data for fragility hip fracture patients
and non-fracture individuals representative of the Australian population. These data together with other bone
quality measures may be of central importance in defining individualised fracture risk assessment and tailorised
treatment efficacy.
Expected future outcomes:
Currently prescribed osteoporosis drug therapies only reduce the risk of fracture by approximately 50%. Novel
bone quality data obtained for fragility fracture patients arising from this project has identified individualised
NHMRC Research Achievements - SUMMARY
responses to osteoporosis drug therapy. Future preventative treatment approaches for primary and secondary
fragility fracture must be considered on an individualised basis.
Name of contact:
Prof Nick Fazzalari
Email/Phone no. of contact:
nick.fazzalari@imvs.sa.gov.au
NHMRC Research Achievements - SUMMARY
Grant ID: 453497
CIA Name: A/Pr Stan Gronthos
Admin Inst: University of Adelaide
Main RFCD: Orthopaedics
Total funding: $485,928
Start Year: 2007
End Year: 2009
Grant Type: NHMRC Project Grants
Title of research award:
The role of TWIST family basic Helix-Loop-Helix transcription Factors in Bone Cell Commitment, Function
and RepairThe role of TWIST family basic Helix-Loop-Helix transcription Factors in Bone Cell Commitment,
Function and Repair
Lay Description (from application):
In developed countries, projected estimates predict an alarming trend of a two to three fold increase in the
number of fractures that require surgical intervention and rehabilitation therapy in the coming decades as a
consequence of an aging population. Fracture healing is a complex physiological process that involves the
coordinated participation of different bone marrow cells, immune cells and skeletal progenitor cells. Multiple
factors regulate interactions between these cell types that influence the capacity of bone cell progenitors to
develop into functional bone forming cells known as osteoblasts. An understanding of the fracture healing is
critical for the future advancement of fracture treatment, and for identifying the mechanisms of skeletal growth
and repair as well as the causes of aging and disease. This proposal seeks to identify critical regulatory
molecules that act to mediate bone cell progenitor recruitment and development during bone fracture repair.
Research achievements (from final report):
, 1. The basic helix-helix-loop (bHLH) transcription factors, Twist-1 and Dermo-1 are known to be important
in normal mesodermal development during embryogenesis. , 2. Our studies showed that Twist-1 and Dermo-1
are highly expressed by human mesenchymal stem cell (MSC) in bone marrow aspirates but are quickly down
regulated folloing ex vivo expansion. , 3. Multiple human bone marrow derived MSC lines were successfully
retrovirally transduced to overexpress either Twist-1 or Dermo-1 in vitro. Functional studies were performed
examining the effect of Twist-1 and Dermo-1 on MSC proliferation, bone gene expression patterns and
differentiation in vitro and in vivo following implantation into NOD/SCID immunocompromised mice., 4.
Enforced expression of Twist-1 and Derrmo-1 was found to maintain the MSC in an undifferentiated state and
greatly increase the growth and lifespan of MSC in vitro., 5. Interestingly, Twist-1 and Dermo-1 inhibited the
capacity of MSC to differentiate into bone and cartilage forming cells , 6. We have established a mouse femoral
bone fracture model for the in vivo analysis of bHLH-transcription factors during bone repair.
Expected future outcomes:
Characterising the role of Twist-1 and Dermo-1 in MSC growth, recruitment and development during fracture
healing may help identify genes that are regulated by Twist-1 and Dermo-1, which can then be used as
therapeutic targets for fracture repair.
Name of contact:
Prof. Stan Gronthos
Email/Phone no. of contact:
stan.gronthos@health.sa.gov.au
NHMRC Research Achievements - SUMMARY
Grant ID: 453510
CIA Name: Prof Howard Morris
Admin Inst: University of Adelaide
Main RFCD: Orthopaedics
Total funding: $543,302
Start Year: 2007
End Year: 2009
Grant Type: NHMRC Project Grants
Title of research award:
Maintenance of bone strength in aged rats: the Vitamin D requirementMaintenance of bone strength in aged
rats: the Vitamin D requirement
Lay Description (from application):
Hip fracture remains the most devastating of the osteoporotic fractures particularly in women in whom the
incidence increases to about 3% per annum by the ninth decade. This incidence is bound to increase as the
population ages with increasing longevity. Supplementation of diets of elderly female nursing home residents
with vitamin D and calcium has been shown to reduce the risk of hip fracture by 30% in two years. However
we do not know how much vitamin D is necessary to maintain optimal bone strength. This project will
determine the level of vitamin D required to maintain optimal bone strength in aged rats using a simple blood
test which could then be used to screen the elderly and identify those at risk of hip fracture from low vitamin D
levels. The project will also investigate the effects of vitamin D on the bone cells that maintain optimal skeletal
architecture. This information is essential for comparison with the current knowledge of other biochemical
bone markets in blood and vitamin D status in the elderly, in order to develop nutritional recommendations to
reduce the incidence of hip fracture.
Research achievements (from final report):
We have described for the first time that the effect of vitamin D depletion is to increase bone resorption and
loss of bone mineral content in this rat model. This study has identified that optimal bone mineral content is not
obtained unless the serum 25D level is greater than 80 nmol/L. Two feeding studies have been completed to
achieve levels above and below the critical values (25D 80 nmol/L) of vitamin D status for bone health as
determined from our first study. Dietary calcium levels have also been varied. Regression analyses
demonstrated significant positive relationships between serum vitamin D levels and bone mineral volume.
Mechanical testing demonstrated that resistance to fracture was positively correlated to vitamin D status.
Furthermore the benefits of high dietary calcium may at least partially be due to the maintenance of higher
serum 25D levels., SIGNIFCANCE: Long-term vitamin D deficiency causes bone loss in both the cortical bone
as well as in trabecular bone resulting in reduced bone strength. Importantly, while vitamin D status is a major
determinant of bone mineral content, both dietary vitamin D and dietary calcium are major determinats of
serum 25D levels. Thus the effect of dietary calcium to protect bone loss appears be due to improvement of
serum 25D levels.
Expected future outcomes:
This dietary model is currently being used to further examine the effects on osteocyte density, apoptosis and
mechanical strength of long bones. Cellular activity in these trabecular and cortical bone regions are being
completed.
Name of contact:
Howard Morris
Email/Phone no. of contact:
howard.morris@health.sa.gov.au
NHMRC Research Achievements - SUMMARY
Grant ID: 453624
CIA Name: Prof Donald Howie
Admin Inst: University of Adelaide
Main RFCD: Orthopaedics
Total funding: $411,517
Start Year: 2007
End Year: 2009
Grant Type: NHMRC Project Grants
Title of research award:
Determination of irradiation dose efficacy for use in impaction grafting at revision joint
replacementDetermination of irradiation dose efficacy for use in impaction grafting at revision joint
replacement
Lay Description (from application):
Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and
require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed
prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is
minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good
results at more than ten years in some centres. A high incidence of early complications of this procedure have
included loss of fixation within the bone. Fracture of the bone around prostheses has also reported in some
centres. These events require more surgery, putting the patient at higher risk greater complications and longer
rehabilitations. Recent improvements in surgical technique and donor bone preparation have improved results.
A current debate questions whether the dose of irradiation can be reduced from 25 kGy, while maintaining
sterility of allografts. The risk of bacterial contamination in allografts is low, and irradiation reduces the
mechanical strength of the graft, contributing to complications when irradiated bone is used. The benefits of
decontaminating the bone may be outweighed by the higher risk for failure due to poor bone quality and
resulting prosthesis instability. We will use ISO standards to test the validity of radiation dose for sterilising
bone ex vivo. In the absence of controlled human studies, our aim is also to compare the results of impaction
grafting with non-irradiated bone versus bone irradiated at current doses used by Australian bone banks, and
lower doses indicated by ex vivo testing. We will use a large animal model of revision hip replacement, with
precise measures of prosthesis stability. The results of this study will guide clinical decisions regarding the
efficacy of current bone graft preparation procedures and the use of irradiated bone in human hip replacement
surgery.
Research achievements (from final report):
This project has led to the direct translation of research findings into clinical practice. Prior to this project the
irradiation dose required by the Queensland Bone Bank for the sterilisation of allograft bone was 25 kGy.
Following publication of the early results from this project, the Therapeutic Goods Administration (TGA)
approved the use of 15kGy for the sterilisation of allograft bone. Subsequent research led to validation of 11
kGy which has now been adopted as the current standard irradiation dose for sterilisation at the Queensland
Bone Bank, settting a precedent for National Bone Bank Guidelines.
Expected future outcomes:
It is envisaged that the results of this important study may encourage more surgeons to use this important bone
restoring procedure.
Name of contact:
Prof Donald Howie
Email/Phone no. of contact:
donald.howie@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 453646
CIA Name: Dr John Semmler
Admin Inst: University of Adelaide
Main RFCD: Central Nervous System
Total funding: $244,255
Start Year: 2007
End Year: 2009
Grant Type: NHMRC Project Grants
Title of research award:
Cortical Plasticity and Fine Motor Skills in Older AdultsCortical Plasticity and Fine Motor Skills in Older
Adults
Lay Description (from application):
Even in healthy individuals, the ageing process is usually associated with a progressive reduction in the
performance of various motor skills, such as writing, placing keys in keyholes and fastening buttons. These
deficits in manual performance may be due to an age-related decline in the ability of the brain to modify its
connections (plasticity) when learning new motor skills. This brain plasticity is a fundamental property of the
nervous system, where it is critical for learning and memory, but is also important for recovery from brain
injury. The goal of the proposed studies is to examine the extent of brain plasticity when performing fine
motor skills in older adults, and relate this to motor performance and learning in the elderly. We will use three
complementary approaches that will employ novel techniques of magnetic brain stimulation to achieve this
goal. These studies will be the first to ascertain a link between deficits in brain plasticity and impaired manual
performance in older adults. Furthermore, these studies will be the first to examine interventions designed to
promote brain plasticity and motor performance in older adults. Because the majority of patients requiring
neurological rehabilitation are in an older age group, it is important to understand the extent of brain plasticity
in the elderly. This new information may ultimately lead to innovative therapeutic or rehabilitation strategies
to retain or improve fine motor skills in the elderly and promote functional recovery from brain injury.
Research achievements (from final report):
The purpose of this project grant was to determine if the decline in fine motor skills commonly observed in
older adults was related to a reduced ability to modify brain connections (termed plasticity) with advancing
age. To achieve this goal, we used new advances in techniques of transcranial magnetic stimulation (TMS) to
assess and induce brain plasticity in young and old adults, and to determine how specific measures of brain
function influence the performance of fine motor skills. We found striking differences in the extent of brain
plasticity and motor performance in young and old adults, but the magnitude of brain plasticity did not relate to
the motor performance in young and old adults. This finding suggests that the deficit in fine motor skills in
older adults was not due to altered brain plasticity with advancing age. Furthermore, we found that older adults
displayed similar brain plasticity as their younger counterparts under some circumstances. We further explored
some factors that could contribute to the similar brain response in older adults, and showed that differences in
physical activity levels and muscle usage patterns related to hand preference could substantially influence the
induction of brain plasticity. By examining the boundary conditions of these effects, this new information may
ultimately lead to innovative therapeutic or rehabilitation strategies to retain or improve fine motor skills in the
elderly and promote functional recovery from brain injury.
Expected future outcomes:
We are now in the process of examining in more detail the boundary conditions that influence brain plasticity
in older adults, such as the contribution of physical exercise, genetics, and alterations in muscle usage patterns
for brain plasticity and motor function.
Name of contact:
John Semmler
Email/Phone no. of contact:
john.semmler@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 508004
Start Year: 2008
CIA Name: Prof Allison Cowin
End Year: 2011
Admin Inst: University of Adelaide
Grant Type: Career Development Fellowships
Main RFCD: Clinical Sciences not elsewhere classified
Total funding: $339,766
Title of research award:
Flightless I, a terget for new wound therapiesFlightless I, a terget for new wound therapies
Lay Description (from application):
Wounds, burns and scalds are frequent injuries which can lead to deformity, disfigurement and loss of
movement. We have shown that the cytoskeletal protein, Flightless I (FliI), is an important regulator of wound
repair. We plan to further investigate FliI in wound and burn injuries using new cell-specific transgenic animal
models and to develop a new FliI-antibody based therapy to treat wound and burn injuries.
Research achievements (from final report):
Chronic wounds, diabetic ulcers, injuries in response to trauma, burns and scalds all form a medical need which
is expanding as the population ages and the diabetic epidemic grows. The overall goal of the research
undertaken during this fellowship was therefore to develop new therapies for improving wound healing and
reducing scar formation. My studies have identified a novel entry point to the study of wound repair and a new
therapeutic target which has been protected by international patents. I have subsequently developed
monoclonal antibodies against this protein which significantly improve healing when applied to wounds.
Preclinical studies have comfirmed the efficiacy of these antibodies for improving the rate of wound healing
and in the quality of scar formation. To date there are limited evidence-based treatments on the market for
improving wound healing so these studies have the potential to dramatically improve the health and well-being
of a substantial number of the population.
Expected future outcomes:
Future outcomes include the development of a new antibody based topical therapy that can be applied directly
to wounds to improve their rate and quailty of healing. This new treatment has applications not only to burn
injuries and acute surgical wounds but also to chronic non-healing ulcers that affect the elderly and diabetic
patients.
Name of contact:
Allison Cowin
Email/Phone no. of contact:
allison.cowin@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 508006
Start Year: 2008
CIA Name: Prof Allison Cowin
End Year: 2010
Admin Inst: University of Adelaide
Grant Type: NHMRC Development Grants
Main RFCD: Clinical Sciences not elsewhere classified
Total funding: $194,071
Title of research award:
Development of Flightless antibody therapy for treating woundsDevelopment of Flightless antibody therapy for
treating wounds
Lay Description (from application):
Chronic wounds, diabetic ulcers, injuries in response to trauma, burns and scalds form a medical need which
will only expand as the population ages and the diabetic epidemic grows. In our studies, we have shown that
Flightless I (FliI), an actin remodelling protein, is a negative regulator of incisional wound healing. We are now
developing a new antibody therapy to reduce FliI levels in wounds thereby leading to improved wound repair
outcomes.
Research achievements (from final report):
, Over the past 6 years, we have investigated the function of the actin-remodelling protein Flightless I (Flii) in
the wound repair process. Our group was the first to show that Flii is an important negative regulator of wound
repair and that attenuation of Flii leads to improved wound outcomes We found that if we reduced the level of
this protein using rabbit polyclonal neutralising antibodie we could significantly improve wound healing in
mouse models of wound repair. Over the last two years, with the support of this NHMRC development grant
we have now generated murine hybridomas against human Flii and have identified three monoclonal antibodies
with wound healing activity in vitro and also in a murine in vivo wound model. Being able to improve the
wound repair process is particularly important as the incidence of non-healing chronic wounds in our society
increases. These wounds are getting more prevalent in our society due to in the increasing numbers of aged,
obese and diabetic individuals who are all at risk of gettingnon-healing wounds. Additionally wounds caused
due to trauma, burns and scald injuries also lead to diffiult to heal wounds so there is a considerable potential
for the development of new therapies for treating wounds. ,
Expected future outcomes:
We expect to produce a new targeted therapy for treating wounds.
Name of contact:
Allison Cowin
Email/Phone no. of contact:
allison.cowin@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 508081
CIA Name: Prof Robert Fraser
Admin Inst: University of Adelaide
Main RFCD: Intensive Care
Total funding: $533,793
Start Year: 2008
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
Impact of gastrointestinal dysmotility on enteral nutrition in the critically illImpact of gastrointestinal
dysmotility on enteral nutrition in the critically ill
Lay Description (from application):
Critically ill patients require nutrition for optimum recovery. Ideally, this is provided via the gut, but
oesophageal reflux, slow gastric emptying and small intestinal dysfunction frequently prevent adequate
delivery of nutrients to these patients, exposing them to complications such as pneumonia and gastrointestinal
bleeding. The work performed by the applicants will improve the ability of doctors in the Intensive Care Unit
to feed patients and prevent the development of such complications.
Research achievements (from final report):
Upper gastrointestinal dysfunction, particularly slow gastric emptying, is common in critically ill patients, and
has been increasingly recognised to be a major contributor to poor outcomes. The work performed during this
grant provided the most definitive studies to date on the mechanisms underlying gastric stasis in these patients,
the contribution of various premorbid and treatment related factors to this condition and the most effective
therapeutic approaches to manage its occurrence. A component of this work included the development,
validation and application of novel measurement techniques in these patients. Additional experiments defined
the role of gastrointestinal dysfunction in glycaemic control, itself an independent risk factor for increased
morbidity and mortality in these patients. Building on this work, innovative studies initially in healthy humans,
but subsequently in patients, provided the first proof of concept studies for the use of incretin therapy,
specifically Glucagon-Like-Peptide (GLP-I), to provide safer treatment options for hyperglycemia in
unconscious patients in the Intensive Care Unit. A corollary to these latter studies was the demonstration that
hormones such as GLP-I are likely to have a major role in the normal physiological feedback regulation of gut
motility after carbohydrate ingestion. Further development of this concept will enhance the development and
utilisation of novel agonists and antagonists to manage abnormalities of glucose metabolism. As well as studies
performed on gastric dysfunction, additional studies demonstrated that disturbed small intestinal motility has a
major impact on nutrient absorption and is also likely to contribute to malnutrition in critical illness.
Expected future outcomes:
Future benefits derived from this grant will enhance nutritional support in critically illness by guiding the
development of novel therapeutic agents to address specific deficits in gastric motor function. In addition this
work will inform development of the novel methods to treat hyperglycamia more safely in these patients.
Name of contact:
Assoc Prof Marianne Chapman
Email/Phone no. of contact:
Marianne.Chapman@health.sa.gov.au
NHMRC Research Achievements - SUMMARY
Grant ID: 508084
CIA Name: Prof Nicola (Nick) Fazzalari
Admin Inst: University of Adelaide
Main RFCD: Orthopaedics
Total funding: $434,498
Start Year: 2008
End Year: 2010
Grant Type: NHMRC Project Grants
Title of research award:
Vertebral body strength: Contribution of bone mass, bone structure and material propertiesVertebral body
strength: Contribution of bone mass, bone structure and material properties
Lay Description (from application):
This study will determine the contributions to vertebral body strength made by its structural and material
properties. Using state-of-the-art computed-tomography scanners, digitised representations of vertebral bodies
in three-dimensions will be produced, which enable measurement of bone structure. After strength testing of
the vertebral bodies, the structural and material properties, which combine to predict vertebral body strength,
will be identified in an aged population.
Research achievements (from final report):
We have successfully developed and implemented protocols for multi-modal and multi-scale imaging
modalities to achieve the project aims. The unique aspect of this study is that each of the complementary bone
structure and material parameters as well as a measure of whole vertebral body bone strength was obtained
from the same specimen. Using current clinically available DXA to meansure area BMD and pQCT to measure
volumetric BMD we validated these clinical data against high-resolution micro-CT imaging. We have
developed and implemented a sub-regional analysis protocol of bone mass at clinical resolution (DXA and
pQCT imaging) against high-resolution micro-CT imaging of whole vertebral bodies (Aims 1 and 4). This
work was performed in conjunction with our associate investigators at the University of Melbourne and is
ongoing with the aim of making the analysis clinically available for patient assessment of vertebral body
fracture risk. We have also shown that a significant proportion of the variability in bone strength can be
explained by cancellous bone morphology and the validation of these observations is about to be published in
Osteoporosis International (Aims 2 and 3). To date the project data has resulted in three peer-reviewed
publications and thirteen conference presentations both nationally and internationally. In additional,
publications highlighting the clinical applicability of our findings are in preparation. Finally, our unique
regional analysis of data from the clinical imaging modalities will inform the clinical guidelines for fracture
risk assessment that will be necessary with new high resolution X-ray based imaging that is currently being
developed for clinical use.
Expected future outcomes:
This work is ongoing within our research program. We are continuing to correlate high-resolution
morphometry and biomechanics, with clinical imaging modalities, with the aim of implementing new improved
clinical imaging protocols to better predict vertebral body fracture risk.
Name of contact:
Prof Nicola (Nick) Fazzalari
Email/Phone no. of contact:
nick.fazzalari@health.sa.gov.au
NHMRC Research Achievements - SUMMARY
Grant ID: 508085
Start Year: 2008
CIA Name: Prof Sharad Kumar
End Year: 2010
Admin Inst: University of Adelaide
Grant Type: NHMRC Project Grants
Main RFCD: Protein Targeting and Signal Transduction
Total funding: $656,396
Title of research award:
Roles of Ndfip1 and Ndfip2 as adaptors for the Nedd4 family of ubiquitin ligasesRoles of Ndfip1 and Ndfip2
as adaptors for the Nedd4 family of ubiquitin ligases
Lay Description (from application):
Part of this proposal is to understand how the body controls iron uptake through one of the iron transporters
(DMT1). We will also study how proteins called Ndfip1 and Ndfip2 that regulate DMT1, also control other
cellular processes, such as protection against brain damage following trauma. The results from this study
should ultimately contribute to the development of therapies for certain human pathologies.
Research achievements (from final report):
In ealier studies we had defined a novel mechanism for the regulation of DMT1, the primary non-heme iron
transporter. This regulation involves the members of the Nedd4 family of ubiquitin ligases and requires the
adaptors Ndfip1 and Ndfip2. In further experiments we used gene knockout in mice to show that Ndfip1deficient mice mice fed a normal iron diet have increased iron stores in the liver and spleen. We also found that
in Ndfip1-deficient mice fed a low iron diet, DMT1 expression and activity were significantly elevated
compared to the wild-type mice. However, despite the increased iron uptake, Ndfip1-deficient mice developed
severe microcytic anaemia due to a combined effect of iron deficiency and inflammatory disease in these
animals. Ndfip1-deficient mice are known to develop severe inflammatory disease, and our new observations
suggest that iron deficiency may accentuate this phenotype. Our results thus provide evidence that Ndfip1 is a
key regulator of DMT1 and iron homeostasis and this regulation may be critical under iron-limiting conditions.
These findings have clear implications in clinical medicine as the combination of iron deficiency and
inflammation is a common clinical problem. Most of the patients suffering with systemic illness such as
systemic lupus erythematosus, inflammatory bowel disease and malignancies frequently develop iron
deficiency either due to low iron intake and/or blood loss. , Using Drosophila as a genetic model system we
also found that Ndfip is a novel regulator of Notch signalling. Notch signaling is frequently dysregulated in
leukemia and other cancers. Thus our finding may be relevent to the understanding of Notch signaling in
human disease.
Expected future outcomes:
We expect to extend our understanding of the roles of Ndfip1 and Ndfip2 in iron homeostasis using mouse
models, focusing on iron recycling pathways and the two iron transporters. This will have direct implications in
understanding diseases of iron transport/metabolism and inflammation.
Name of contact:
Sharad Kumar
Email/Phone no. of contact:
sharad.kumar@health.sa.gov.au
NHMRC Research Achievements - SUMMARY
Grant ID: 508087
Start Year: 2008
CIA Name: Prof Stan Gronthos
End Year: 2012
Admin Inst: University of Adelaide
Grant Type: NHMRC Research Fellowships
Main RFCD: Biochemistry and Cell Biology not elsewhere classified
Total funding: $570,218
Title of research award:
Uncoupled Research FellowshipUncoupled Research Fellowship
Lay Description (from application):
I am a stem cell biologist researching the properties and application of mesenchymal stem cells, with an aim to
develop cellular based therapies for repairing mineralised tissues such as bone, cartilage, dentin, cementum and
other connective-supportive ti
Research achievements (from final report):
N/A
Expected future outcomes:
N/A
Name of contact:
Prof. Stan Gronthos
Email/Phone no. of contact:
stan.gronthos@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 508097
CIA Name: A/Pr Stuart Pitson
Admin Inst: University of Adelaide
Main RFCD: Cell Physiology
Total funding: $281,340
Start Year: 2008
End Year: 2010
Grant Type: NHMRC Project Grants
Title of research award:
The role of SKAM and sphingosine kinase in wound healingThe role of SKAM and sphingosine kinase in
wound healing
Lay Description (from application):
Many aspects of wound healing are poorly understood. We have identified a novel cellular pathway that
appears critically involved in controlling wound contraction. This project aims to characterise this cellular
pathway to understand the exact mechanisms whereby it controls this critical aspect of wound healing. With
this information we will develop topical therapeutics to aid the wound healing process.
Research achievements (from final report):
Many aspects of wound healing are poorly understood. We have identified a novel cellular pathway that
appears critically involved in controlling wound contraction. This project aimed to characterise this cellular
pathway to understand the exact mechanisms whereby it controls this critical aspect of wound healing. To this
end we have demonstrated that the SKAM protein is elevated in tissues after wounding and enhances wound
contraction by its activation of the sphingosine kinase enzyme and subsequent formation of the bioactive lipid
sphingosine phosphate. We have used the fundamental knowledge gained to developed novel small molecule
activators to enhance the wound contraction process for potential development as a topical therapeutic to aid
the wound healing process.
Expected future outcomes:
The knowledge gained from these fundamental studies will be applied to further develop novel small molecule
activators and inhibitors to control the wound contraction process for potential development as a topical
therapeutics to aid the wound healing process and reduce scaring.
Name of contact:
A/Prof Stuart Pitson
Email/Phone no. of contact:
stuart.pitson@health.sa.gov.au
NHMRC Research Achievements - SUMMARY
Grant ID: 519211
Start Year: 2008
CIA Name: Dr Mark Gibson
End Year: 2012
Admin Inst: University of Adelaide
Grant Type: NHMRC Project Grants
Main RFCD: Cellular Interactions (incl. Adhesion, Matrix, Cell Wall)
Total funding: $690,876
Title of research award:
Function of matrix proteins important for storage and activation of TGF and TGF -induced tissue remodelling
and repairFunction of matrix proteins important for storage and activation of TGF and TGF -induced tissue
remodelling and repair
Lay Description (from application):
The growth factor TGF is important for tissue development and repair, and in diseases such as pulmonary
fibrosis, glomerulonephritis, liver cirrhosis, keloid formation and cancers. This project focuses on 2 important
matrix proteins first discovered by Dr Gibson, LTBP-2 and ig-h3, that modulate TGF storage and TGF induced tissue remodelling . We will use knock out mouse and cell culture models to determine the function of
these proteins in tissue development and repair, and in diseases.
Research achievements (from final report):
The grant has enabled my laboratory to define several molecular functions of extracellular matrix protein,
LTBP-2. Four heparan sulphate binding sites have been mapped on the LTBP-2 molecule and LTBP-2 was
found to inhibit the elastin precursor, tropoelastin in its interactions with fibulin-5 and heparan sulphate. These
findings increase our understanding the mechanism of elastic fibre assembly, a process important for the
function of tissues such as arteries, lung and skin. LTBP-2 was also found contain a single high-affinity
binding site for FGF-2, a potent growth factor implicated in fibrotic diseases. Moreover, addition of exogenous
LTBP-2 to several cell lines showed a marked stimulation of growth factor TGF-beta expression in the cells.
The activity was mapped to a small central region of LTBP-2. These findings prompted us to screen several
fibrotic skin disorders for LTBP-2. Using immunohistochemistry we showed increased staining in hypertrophic
scar tissue particularly keloids, suggesting a link between LTBP-2 levels and fibrosis.
Expected future outcomes:
The research has prompted a new grant application to investigate LTBP-2 in fibrotic diseases.
Name of contact:
Mark Gibson
Email/Phone no. of contact:
mark.gibson@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 519220
Start Year: 2008
CIA Name: Prof Jane Mathias
End Year: 2014
Admin Inst: University of Adelaide
Grant Type: NHMRC Project Grants
Main RFCD: Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology)
Total funding: $874,405
Title of research award:
Diagnostic and prognostic evaluation of diffusion tensor imaging and cognitive function after traumatic brain
injuryDiagnostic and prognostic evaluation of diffusion tensor imaging and cognitive function after traumatic
brain injury
Lay Description (from application):
Traumatic brain injuries (TBIs) are a common cause of brain damage, leading to a variety of disabling
cognitive problems. This study will evaluate the ability of new brain imaging techniques and cognitive tests to
detect previously undiagnosed brain damage and to predict patient outcome following TBI in order to improve
the health care and treatment of these patients. It will also examine the contribution of other factors (eg. injury
type, age, pre-injury cognitive ability) to outcome.
Research achievements (from final report):
Traumatic brain injuries TBIs - sustained as a consequence of motor vehicle accidents falls sports and assaults
etc - are often associated with long-term problems which can place a heavy burden on our health and welfare
systems. However the methods that have been used to assess the brain damage caused by these injuries have
thus far proven inadequate seriously limiting our diagnostic and prognostic accuracy particularly in the case of
mild injuries. Important variables that may impact on outcome- such as the cause of an injury - have frequently
also been overlooked. This study used a recently developed magnetic resonance imaging MRI method Diffusion Tensor Imaging DTI - to assess structural damage to the white matter tracts of the brain in order to
examine how well it predicts the outcomes of people who have sustained mild moderate or severe TBIs.
Orthopaedic and community samples were additionally assessed for comparative purposes. Thus far we have
developed automated strategies to identify white matter tracts and measure diffusion and established its
reliability over-time and between imaging machines and begun evaluating the real-world consequences of this
damage. We have also compared orthopaedic and community controls - which has not previously been done
with orthopaedic controls having been assumed to be superior - and found that the two were very comparable.
Moreover our analysis suggests that injury-cause may explain some of the differences in the outcomes of
people who have seemingly comparable injuries. Involvement in litigation and the cause of an injury may also
be confounded which can lead to the erroneous conclusion that litigants have poorer outcomes.
Expected future outcomes:
Continued improvements to diagnostic and prognostic accuracy will help ensure that those who are at greatest
risk of poor long-term outcomes receive early treatment and interventions as well as continued monitoring in
order to ensure that their outcomes are optimised and that the TBI-related 'burden of disease' is minimised.
Name of contact:
Prof J Mathias
Email/Phone no. of contact:
jane.mathias@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 519223
CIA Name: Prof Donald Howie
Admin Inst: University of Adelaide
Main RFCD: Orthopaedics
Total funding: $192,187
Start Year: 2008
End Year: 2010
Grant Type: NHMRC Project Grants
Title of research award:
Radiostereometric analysis of the effect of a large articulation on prosthetic wear and migration after hip
replacementRadiostereometric analysis of the effect of a large articulation on prosthetic wear and migration
after hip replacement
Lay Description (from application):
At total hip replacement, there has been a recent trend to use prostheses with a larger ball and liner in the
socket. This may decrease the risk of post-operative dislocation, but may also increase the amount of wear,
leading to bone loss and loosening of prostheses, which may then require replacement. This project will use a
special type of x-ray to determine whether wear and movement of these new prostheses is clinically acceptable,
so that they can be used with confidence in patients.
Research achievements (from final report):
Large articulations in total hip replacement are increasingly being used. We have previously shown in an
NHMRC-funded randomised trial that a large articulation significantly reduces the risk of dislocation following
hip replacement. Although new polyethylene liners have made the use of larger articulations feasible, whether
larger articulations were associated with significant amounts of polyethylene wear was not known. Significant
polyethylene wear results in polyethylene particulate debris being deposited around the hip replacement
prosthesis which can then lead to localised bone loss, requiring costly revision of the total hip replacement with
its associated risks of both death and complications. We used a highly sophisticated radiographic technique,
namely radiostereometric analysis, to measure early polyethylene wear, which can not be seen on plain
radiographs. Our study has shown that the wear between one and two years of the large metal on highly crosslinked polyethylene articulations now commonly used in total hip replacement are similar to those of the
standard-sized articulations and within the clinically acceptable range of wear. Therefore, these articulations
can now be recommended for more general use. However, continued monitoring of wear is required to ensure
that there is no unexpected increase in wear over time.
Expected future outcomes:
Wear of metal on highly cross-linked polyethylene articulations will continue to be examined to determine the
longer term wear associated with these hip replacements.
Name of contact:
Dr Oksana Holubowycz
Email/Phone no. of contact:
oksana.holubowycz@health.sa.gov.au
NHMRC Research Achievements - SUMMARY
Grant ID: 519248
CIA Name: Prof Robert Vink
Admin Inst: University of Adelaide
Main RFCD: Central Nervous System
Total funding: $589,789
Start Year: 2008
End Year: 2010
Grant Type: NHMRC Project Grants
Title of research award:
Raised intracranial pressure after trauma: characterisation and development of pharmacological
interventionsRaised intracranial pressure after trauma: characterisation and development of pharmacological
interventions
Lay Description (from application):
Raised intracranial pressure (ICP) commonly occurs after traumatic brain injury (TBI) and is thought to be
responsible for up to 50% of all mortality, as well as significantly contributing to the persistent neurological
deficits in survivors. Few studies have examined the dynamics of raised ICP after TBI, or its effects on brain
oxygenation. This study will fully characterize changes in ICP and brain oxygen after TBI and develop novel
treatments to control such changes.
Research achievements (from final report):
Our goal was to determine whether small or large animal models are the most appropriate for the study of
intracranial pressure (ICP) changes after traumatic brain injury (TBI), and then to assess the effectiveness of
several current and potential drug therapies in the most appropriate model. Our results showed that rodent
models do not reliably replicate the human ICP condition after TBI and that a large animal model is a far
superior model of human TBI. We then demonstrated that current therapies such as mannitol and hypertonic
saline are effective in reducing ICP, but that they did not substantially increase brain tissue oxygenation.
Magnesium and Progesterone were ineffective with respect to both measured parameters. In contrast, substance
P anatgonists were highly effective in reducing elevated ICP and restoring brain oxygen levels to normal after
TBI. We now have a complete understanding of ICP/brain oxygenation dynamics after TBI and the ability to
develop and assess novel pharmacological interventions in a highly effective, large animal model of TBI. We
also have developed one novel pharmacological intervention that appears to be the first ever to effectively
control ICP and improve brain oxygenation after severe TBI.
Expected future outcomes:
We will now endeavour to obtain funding for studies that will establish the dose-response relationship and
therapeutic window for the substance P antagonists in our large animal model of TBI. This will greatly
facilitate translation to the clinical situation.
Name of contact:
Professor Robert Vink
Email/Phone no. of contact:
Robert.Vink@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 565004
CIA Name: Prof Allison Cowin
Admin Inst: University of Adelaide
Main RFCD: Dermatology
Total funding: $545,216
Start Year: 2009
End Year: 2012
Grant Type: NHMRC Project Grants
Title of research award:
Mechanism of Flightless I function in burn injury and scar formationMechanism of Flightless I function in burn
injury and scar formation
Lay Description (from application):
Extensive scarring is a major clinical problem often resulting from burn injuries. We have previously shown
that the cytoskeletal protein, Flightless I (FliI), is an important regulator of wound repair. We now plan to
investigate whether FliI is also be the mechanistic link between cytoskeletal remodelling and induction of
TGF-betas post-wounding leading to scar formation.
Research achievements (from final report):
Wounds, burns and scalds are frequent injuries which inevitably lead to scarring and contracture resulting in
deformity, disfigurement and loss of movement. The development of new therapies which improve healing and
reduce scarring would significantly improve the health of many people who suffer horrific burns. Our previous
NHMRC funded research identified that the cytoskeletal protein Flightless I (Flii) is an important negative
regulator of wound healing. Here we investigated whether Flii was the mechanistic link between cytoskeletal
remodelling and the induction of pro-scarring TGF-?s which lead to fibrosis and scar formation. Using in vitro
and in vivo models of scarring and fibrosis we addressed the important issue of whether Flii deficiency
improved burn injury and decreased scar formation. Using our established murine burn injury model and a new
dermal fibrosis model we assessed the effect of Flii on burn injury repair and scarring. These studies revealed
that overexpression of Flii significantly impaired burn injury repair and that exogenous application of Flii
neutralizing antibodies which reduced the level of Flii in the burn wound environment improved healing and
reduced fibrosis. A follow on study also investigated the role of Flii in hair follicle regeneration post burn
injury as regeneration of hair and other dermal appendages is a significant issue for patients with burn injuries.
The benefit of being able to reduce Flii in burns and fibrotic skin conditions and reduce the incidence and
severity of scarring is of great importance for the Australian community particularly for children suffering from
burn injuries.
Expected future outcomes:
New burn wound therapies based around reducing the level of Flii in wounds is a major future outcome of this
work. We are working with biomaterial scientists in order to develop new wound dressings that can deliver Flii
neutralising antibodies to large surface areas as occurs in burns.
Name of contact:
Allison Cowin
Email/Phone no. of contact:
allison.cowin@unisa.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 565176
Start Year: 2009
CIA Name: Prof Stan Gronthos
End Year: 2011
Admin Inst: University of Adelaide
Grant Type: NHMRC Project Grants
Main RFCD: Biochemistry and Cell Biology not elsewhere classified
Total funding: $579,138
Title of research award:
The Role of Eph-ephrin Interactions in Mediating Mesenchymal Stem Cell Commitment, Migration and Bone
Fracture RepairThe Role of Eph-ephrin Interactions in Mediating Mesenchymal Stem Cell Commitment,
Migration and Bone Fracture Repair
Lay Description (from application):
In Australia, there is an increasing incidence of fractures that require surgical intervention and rehabilitation
therapy. Fracture healing is a complex process that involves the coordination of different bone and immune
cells. Our proposal will identify which cell-cell contact molecules mediate bone cell recruitment and
development during normal skeletal growth and bone fracture repair. This study will help advance therapies for
fracture repair and diseases of bone loss.
Research achievements (from final report):
1. We have identified several B class Eph and ephrin molecules as being highly expressed by mesenchymal
stem cells (MSC)., 2. We have identified the role of B class EphB2 in human MSC migration, EphB4 and
ephrinB1 in human MSC bone formation, ephrinB1 and ephrinB2 in human MSC cell attachment/spreading., 3.
We have characterised the Eph/ephrin gene and protein expression pattern during fracture repair., 4. We have
completed the femoral fracture healing experiments using EphB4 overexpressing transgenic mice driven by the
collagen typeI promoter. , Collectively, these studies show that Eph/ephrin moleculaes are mediators of bone
cell growth, migration and function.
Expected future outcomes:
Knowledge gained from this study has increased our understanding of the factors that regulate bone progenitor
cell growth and differentiation. The study has provided potential molecular targets to enable the future
development of novel therapies that regulate endogenous MSC growth and differentiation to enhance bone
regeneration during fracture repair.
Name of contact:
Prof. Stan Gronthos
Email/Phone no. of contact:
stan.gronthos@health.sa.gov.au
NHMRC Research Achievements - SUMMARY
Grant ID: 565361
CIA Name: A/Pr David Haynes
Admin Inst: University of Adelaide
Main RFCD: Orthopaedics
Total funding: $403,639
Start Year: 2009
End Year: 2012
Grant Type: NHMRC Project Grants
Title of research award:
Regulation of key pathways causing peri-implant bone loss.Regulation of key pathways causing peri-implant
bone loss.
Lay Description (from application):
The failure of bone prostheses is becoming a major health problem in our aging population. Despite the
impressive success of joint replacement surgery, a significant number of arthroplasties fail. It is now apparent
that most implants fail due to bone loss around them which leads to loosening. This project aims to obtain a
better understanding of the causes of implant failure and find ways to extend the life of these implants .
Research achievements (from final report):
We have developed two new ways of understanding why implants fail. The first is an animal model of the
pathology that uses state of the art live animal CT scanning to assess bone loss. The second allows us to look at
the way cells respond to implant materials in a way that more closely resembles what happens in the patient.
We have used these techniques to understand what factors and cells are causing the bone loss. These findings
have nearly all been published and/or presented at international scientific meetings in the field. The findings
influence those deciding on the best type of materials to use in hip replacements and other joint implants.
Expected future outcomes:
The eventual failure of hip replacements results in high cost and morbidity. The results of the study will
influence surgeons and materials scientists as they show the vulnerability of traditional polyethylene implants
to failure. These findings will enhance the transition to newer, low wear, materials (eg. HXLPE) in the clinic.
Name of contact:
David R Haynes
Email/Phone no. of contact:
david.haynes@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 626910
Start Year: 2010
CIA Name: Prof Stan Gronthos
End Year: 2012
Admin Inst: University of Adelaide
Grant Type: NHMRC Project Grants
Main RFCD: Biochemistry and Cell Biology not elsewhere classified
Total funding: $605,096
Title of research award:
Twist-1 Mediated Regulation of Multipotential Mesenchymal Stem Cell Self-Renewal and Cell Fate
DeterminationTwist-1 Mediated Regulation of Multipotential Mesenchymal Stem Cell Self-Renewal and Cell
Fate Determination
Lay Description (from application):
In Australia, there is an increasing incidence of fractures and skeletal related problems that require surgical
intervention and rehabilitation therapy. These are complex processes that involve the coordination of different
bone and immune cells. We will investigate important regulatory molecules that mediate bone-cartilage stem
cell recruitment and development during normal skeletal growth and remodelling. This study will help advance
therapies for fracture repair and joint deterioration.
Research achievements (from final report):
Human mesenchymal stem cells (MSC) are progenitors to all the connective tissue types associated with the
skeleton (cartilage, bone, fat and muscle) and are now being assessed in the clinic for their efficacy in different
regenerative medicine applications. Our laboratory is examining the genes that regulate MSC growth and
differentiation. 1. We have shown that the Twist-1 and Twist-2 (DERMO-1) genes are highly expressed by
STRO-1bright immature human MSC but are quickly down regulated during ex vivo expansion. 2. Viral
mediated enforced expression of Twist-1 and -2 increases the life span of human MSC by almost three fold.
The genetically modified MSC express higher levels of the immature marker, STRO-1, and lower levels of the
mature osteoblast marker, alkaline phosphatase. 3. Microarray analysis of the gene expressed by Twist-1 over
expressing and control MSC has identified putative gene targets that may be involved in the cell fate
determination and self-renewal capacity of MSC regulated by Twist-1. 4. We have found that MSC
overexpressing Twist-1 and -2 were reduced in their capacity to form bone and cartilage in vitro and in vivo,
but exhibited an increased capacity to undergo adipogenic differentiation.5. We are in the process of assessing
the bone healing rates in a femoral fracture model using Twist-1 mutant mice.
Expected future outcomes:
These studies will determine the molecular pathways regulated by Twist genes that are involved with MSC
growth and differentiation. These molecular pathways can then be targeted by drugs or growth factors to
manipulate the manufacture of MSC ex vivo for therapeutic apllications.
Name of contact:
Prof Stan GronthosProf. Stan Gronthos
Email/Phone no. of contact:
stan.gronthos@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 627198
CIA Name: Prof Robert Vink
Admin Inst: University of Adelaide
Main RFCD: Central Nervous System
Total funding: $412,461
Start Year: 2010
End Year: 2013
Grant Type: NHMRC Project Grants
Title of research award:
Shaken baby syndrome: characterization of a model and evaluation of novel pharmacological therapiesShaken
baby syndrome: characterization of a model and evaluation of novel pharmacological therapies
Lay Description (from application):
Shaken baby syndrome is a form of traumatic brain injury in infants less than 2 years of age. It results in death
in 10-40 % of cases, and neurological problems in survivors. No treatment exists largely because there is no
well characterized model of the syndrome that replicates the human situation. This study will fully characterize
our newly developed model of shaken baby syndrome and examine the effectiveness of a novel interventional
strategy targeting brain swelling.
Research achievements (from final report):
Non-accidental head injury (NAHI), also termed the "shaken baby syndrome", is a major cause of death and
severe neurological dysfunction in children under 3 years of age. Sadly, no treatment has been developed for
victims of NAHI, largely because inadeqaute models currently exist for drug development and screening. In the
present study, we were able for the first time to develop a clinically relevant large animal, ovine model of
NAHI, that reproduces the neuropathology and ocular injury seen in human NAHI. Moreover, we showed that
shaking alone in this model was sufficient to reproduce the syndrome, and was in fact lethal in the case of
smaller subjects, a finding of major medical and medicolegal significance. Neuropathological assessment
showed that animals subject to NAHI had increased blood brain barrier permeability, which was associated
with substance P release and brain swelling. Surprisingly, there was no significant increase in intracranial
pressure with brain swelling, most likely because of the pliable nature of the underdeveloped skull. The
development of this clinically relevant model will now permit screening of potential treatment interventions.
Expected future outcomes:
As the first clinically relevant model of NAHI, this ovine model will allow scientists to develop and screen
novel pharmacotherapies targeted at the specific injury factors identified and characterised in this model. On
the basis of our initial results, substance P has been confirmed as a novel first target.
Name of contact:
Professor Robert VinkProfessor Robert Vink
Email/Phone no. of contact:
Robert.Vink@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 284343
CIA Name: Prof Caroline Finch
Admin Inst: University of Ballarat
Main RFCD: Epidemiology
Total funding: $646,540
Start Year: 2004
End Year: 2008
Grant Type: Established Career Fellowships
Title of research award:
Uncoupled Research FellowshipUncoupled Research Fellowship
Lay Description (from application):
Not Available
Research achievements (from final report):
My research into the prevention of injuries during sport has made a significant contribution to the health and
wellbeing of Australians. I have identified injury priorities and evidence-based strategies for their prevention
that have since been adopted by national/state/local sports bodies, government departments and health
agencies. My research has firmly established sports safety as a significant public health issue; quantified the
magnitude of the problem in Australia; developed and applied high quality epidemiological methods; placed
sports injury prevention within broader public health strategies to promote physical activity and ongoing sports
medicine development. My research has clearly demonstrated that sports bodies will not implement safety
policies until they are sure that safety measures actually prevent injuries, are acceptable to their participants, do
not change the essential nature/appeal of sport, and do not adversely affect participation/performance. Through
investigation of the sports implementation setting, my research has provided new understanding of the sports
and individual athlete behaviour contexts in which the interventions are to be implemented and has assessed
potential factors associated with the real-world introduction and application of safety measures and
development of implementation strategies to accompany the real world ''rollout'' of safety interventions.
Underpinning all of the above research is a need for high quality, reliable injury statistical data through
surveillance activities. I have also undertaken significant research into sports and falls injury surveillance and
made methodological advances in the design of injury surveillance systems, as well as contributing to
international debate about how to code and classify injuries.
Expected future outcomes:
My research will continue to make ongoing significant contributions to sports safety in Australia through
providing a strong evidence-base for developing sport safety measures and related policy initiatives. Most
importantly, they have focussed attention on better understanding of the sports context to enhance the adoption
of safety measures.
Name of contact:
Prof Caroline Finch
Email/Phone no. of contact:
c.finch@ballarat.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 565900
Start Year: 2009
CIA Name: Prof Caroline Finch
End Year: 2013
Admin Inst: University of Ballarat
Grant Type: NHMRC Research Fellowships
Main RFCD: Public Health and Health Services not elsewhere classified
Total funding: $702,604
Title of research award:
Uncoupled Research FellowshipUncoupled Research Fellowship
Lay Description (from application):
I am an epidemiologist with a particular interest in injury prevention, injury data systems and safety promotion
as they apply to the context of sports injury. I also contribut to the broager field of epidemiology, through the
theoretical and methodilogic
Research achievements (from final report):
My public health-focused research ensures that all Australians can benefit from the health and social benefits of
participating in safe sport, through the generation and dissemination of new evidence to underpin effective
sports injury prevention strategies. My research has been designed from the outset to ensure that it both directly
impacts on the real-world settings in which sports injury prevention must be implemented and is relevant for
the Government/national NGO stakeholders responsible for setting sports safety policy. My research has
focussed on broad community sports participation, not elite athletes. Drawing on my biostatistical and
epidemiological background, my research always has a strong methodological base reflected in the design and
analysis of surveys/questionnaires; development and refining of surveillance/injury monitoring systems/data
coding schemes; statistical modelling of longitudinal injury data; conduct of cohort studies to identify injury
risk factors and to monitor sports injury incidence; assessment of intervention effectiveness through clusterrandomised controlled trials; and application of behavioural/health promotion frameworks/models to the
evaluation of implemented sports safety measures. I have led international efforts in the application of
implementation science applications to sports medicine and qualitative studies into safety policy and practice.
As the head of 1 of 4 global International Olympic Committee Research Centres for Injury Prevention &
Promotion of Athlete Health, my work has contributed to injury surveillance/statistical modelling and
implementation/dissemination research as they relate to the national and international sports medicine priorities
of lower limb/tendinopathy/overuse injury and head injury/concussion prevention.
Expected future outcomes:
More people will be able to participate in sport and physical activity because it is safer for them to do so. My
research will continue to inform policy development and implementation of safety programs by sports bodies
and government agencies for years to come, as well as evaluate their success.
Name of contact:
Professor Caroline Finch
Email/Phone no. of contact:
c.finch@federation.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 145634
CIA Name: A/Pr Colin Anderson
Admin Inst: University of Melbourne
Main RFCD: Autonomic Nervous System
Total funding: $241,528
Start Year: 2001
End Year: 2003
Grant Type: NHMRC Project Grants
Title of research award:
Determination of sympathetic preganglionic neuronal phenotypeDetermination of sympathetic preganglionic
neuronal phenotype
Lay Description (from application):
The nervous system is the single most complex part of our body. Its function depends on millions of
connections between neurons, all of which must form correctly during development. Furthermore, each neuron
must select a neurotransmitter with which to "talk" to its target neuron. A neurotransmitter is a chemical
released from a neuron, which passes a signal to a target cell. Some neurotransmitters cause excitation of the
target cell, others inhibition. Each neurotransmitter signals to the target cell via receptor molecule, matched to
the neurotransmitter. Thus, a neuron is faced not only with making choices about what connections to make
within the developing brain, but also it must select from a range of potential neurotransmitters and receptor
molecules. We are interested in how neurons select the appropriate neurotransmitter. There are a number of
ways that a neuron might be guided to the correct choice. It is possible that it could receive from the target cell
a signal that guides the choice of neurotransmitter. We wish to examine this hypothesis to see if it is applicable
to the autonomic nervous system, that part of the nervous system that controls functions like changes in blood
pressure and heart rate. Our laboratory is expert in identifying the chemistry of autonomic neurons. We will use
this knowledge to see what happens when we deliberately perturb the normal connections of autonomic
neurons. Do they persist in expressing the neurotransmitters they would have done prior to the perturbation?
Alternatively, do they adapt to the change of target via a signal received from the new target cell and express
the appropriate phenotype? The results of these experiments will give insights into how the brain develops. The
results will be important for both our basic understanding of biology and as a basis for the development of
techniques for reversing neuronal damage.
Research achievements (from final report):
The nervous system contains many types of neurons. During development, each type of neuron must be
generated in the correct place and in the appropriate numbers. We focused on one aspect of how this may
occur. When a neuron extneds an axon to contact a target tissue, the target tissue can instruct the neuron as to
which genes to swtich on or switch off in order to generate the type of neuron appropriate for that target tissue.
We have looked for evidence that this process occurs in the peripheral nervous system by exposing neurons to
novel targets to see if the neuron can respond by changing its phenotype to match the new target. We have
produced evidence that sympathetic preganglionic neurons can respond to the presence of one of their normal
target tissues when it is chifted to a novel location. Preganglionic neurons that come to innervate the target in
the new location adopt the phenotype of neurons that would have innervated the adrenal chromaffin tissue in its
normal location. We have gone on to show that the same thing happens when a normal target of the
postganglionic sympathetic neurons, the pineal gland, is transplanted to a new location. Again, the innervating
neuron adopt a phenotype appropriate for the new target tissue.
Expected future outcomes:
This knowledge is important as much effort is currently being expended on generating new neurons from stem
cells for use in repairing human nervous systems damaged by trauma or disease. To succeed, it will be
necessary to generate specific types of neuron from the stem cells in a controlled way and the our study will
contribute to an understanding of the biological mechanisms involved.
Name of contact:
Assoc Prof Colin Anderson
Email/Phone no. of contact:
NHMRC Research Achievements - SUMMARY
c.anderson@unimelb .edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 145654
CIA Name: Dr Pritinder Kaur
Admin Inst: University of Melbourne
Main RFCD: Dermatology
Total funding: $212,037
Start Year: 2001
End Year: 2003
Grant Type: NHMRC Project Grants
Title of research award:
Developmental potential of murine keratinocyte stem cellsDevelopmental potential of murine keratinocyte
stem cells
Lay Description (from application):
The stem cells of the epidermis or outer lining of the skin are an important group of cells with a role in normal
cell replenishment, in wound healing and in skin disorders such as psoriasis and cancer. These primitive cells
remain in the skin during the lifetime of an individual and are responsible for the production of mature,
functional cells that form a protective barrier against the environment and pathogens. We have recently
developed a strategy for the isolation of stem cells of the skin which places us in a unique position to further
study these cells and determine possible therapeutic approaches for the future. The aims of this project
encompass testing the potency of skin stem cells (i) to reform complex structures such as a mature epidermis,
hair follicles and sebaceous glands; and (ii) to give rise to cells from other tissues such as muscle and liver. A
final aim of this project is to dissect the complexity of the stem cell compartment further to gain insights into
how normal skin growth is regulated.
Research achievements (from final report):
The work we have performed has been aimed at gaining a greater understanding of the properties of stem cells
of the skin, particularly those stem cells that exist in the outer lining of the body (epidermis or epithelia) that
interfaces with the environment. Currently there are no experimental systems that are capable of measuring the
long-term activity of epithelial stem cells - many assays or techniques that are currently thought to show stem
cell behaviour are in fact too short-lived to allow us to sistinguish stem cells from other epithelial progenitor
cells. Our study has resulted in the development and optimisation of transplant models for analysing skin tissue
regeneration as a measure of stem cell activity. This study has also encompassed testing whether stem cells of
the skin can be isolated by staining with a Hoechst dye (Hoechst 33342) and simply collecting those cells that
have an ability to get rid of the dye (dye-effluxing cells identified as Hoechst dull cells). This work shows that
although Hoechst dull cells can be found in the epidermis, further work is required to determine if these cells
are stem-cell like. We have been able to optimise culture conditions to allow us to start analysing these cells
both in culture and in transplants to begin answering these questions.
Expected future outcomes:
A greater understanding of the biological properties of epidermal stem cells of the skin is needed to devise
means for their growth in the clinic for patients that have severe wounds (such as burns) and need skin
replacement. Our work will result in the development of techniques that facilitate stem cell isolation and
cultivation
Name of contact:
Pritinder Kaur
Email/Phone no. of contact:
pritinder.kaur@petermac.org
NHMRC Research Achievements - SUMMARY
Grant ID: 145820
CIA Name: Prof Ego Seeman
Admin Inst: University of Melbourne
Main RFCD: Endocrinology
Total funding: $196,018
Start Year: 2001
End Year: 2003
Grant Type: NHMRC Project Grants
Title of research award:
Apportioning deficits in bone size and density in women with fractures to growth or ageing by studies in their
daughtersApportioning deficits in bone size and density in women with fractures to growth or ageing by studies
in their daughters
Lay Description (from application):
Women fracture their bones because the bones are small and break easily and because the bones are thin or low
in denseness (very porous like a honey comb). This study is aimed at identifying why women with fractures
have small bones and why the bones are so porous. They may have these problems because they lost a lot of
bone as they get older or because growth was abnormal so the size of the bone didn't reach its potential size or
because the denseness of the bones didn't develop properly. The study will be carried out in women with spine
or hip fractures and their daughters. All participants will have bone densitometry, provide a 24 hour urine
sample and a fasting blood sample of 20 ml whole blood. Informed consent will be obtained from all
participants. The bone density scan is associated with radiation exposure of about 4 mSv, about one tenth of a
chest x ray, temporary bruising may follow taking blood. If we can understand the different ways
osteoporosis can occur we can then start to devise specific treatments tailored to the individual. Also if we can
identify the causes of small bones and bone thinness during growth it may be possible to correct some of these
causes before the reduced growth and reduced building of bone occurs. We might also prevent the thinning of
bone by identifying and removing causes of bone thinning.
Research achievements (from final report):
The aim of this study is to determine if the deficits in bone mass and size in women with spine or hip fractures
are growth-related (reduced bone accrual during growth), age-related (excessive bone loss), or a combination
of the two., , Women with spine fractures have low bone density at the spine, which is likely due to reduced
accrual during growth, as the deficits in their daughters' bone density were about half that of their mother's.
However, the lower vertebral size in women with spine fractures is likely to occur during aging, as their
daughters do not have deficits in vertebral size., , Women with hip fractures have larger femoral neck bone
size, lower bone density and a thinner bone. Daughter of women with hip fractures also had larger femoral
neck bone size, but normal bone density and normal bone thickness. Therefore, we infer that the larger bone
size in women with hip fractures is growth-related, but the reduction in bone density and thinning of the bone
occurs during aging. Fragility fractures at the spine and hip have their origins in both growth and aging., , The
results of this study should influence how osteoporosis is viewed and the approach taken to research, prevent
and treat osteoporosis. Approaches need to look beyond just factors influencing bone density during aging, to
also include factors that affect bone density during growth and influence bone size and structure. The major
shift appears to be from treatment in adulthood, to prevention and risk assessment during both growth and
aging.
Expected future outcomes:
The results of this study open new approaches to research into the pathogenesis and prevention of bone
fragility. Drug therapy may need to be different in persons with deficits due to low peak accrual versus those
with excessive bone loss. Approaches to the whole of the population during growth and aging are needed just
as cardiovascular disease prevention is increasingly focussed at children.
Name of contact:
Ego Seeman
Email/Phone no. of contact:
egos@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 145828
CIA Name: A/Pr Thomas Cocks
Admin Inst: University of Melbourne
Main RFCD: Basic Pharmacology
Total funding: $486,943
Start Year: 2001
End Year: 2005
Grant Type: NHMRC Project Grants
Title of research award:
Characterisation of PAR2 knockout and transgenic mice: towards gene therapy for epithelia based
inflammatory diseasesCharacterisation of PAR2 knockout and transgenic mice: towards gene therapy for
epithelia based inflammatory diseases
Lay Description (from application):
Debilitating and sometimes fatal diseases like asthma and rheumatoid arthritis urgently require new approaches
for their effective management and hopefully, cure. We have recently discovered that the airways posses a
powerful and naturally-occuring protective mechanism which is regulated by unique molecules in the
membranes of the lining cells of the air passages. These molecules are called protease-activated receptors, or
PARs, and are also found on cells lining the inner surfaces of blood vessels and joints as well as in skin. We are
fortunate to have strains of mice - a species in which the PAR-mediated protective mechanism is well
developed - in which the gene for the most important of the PARs found in the lung, PAR2, is missing. These
animals are called PAR2 'knock-outs'. We also have another strain of mouse in which the human PAR2 gene
has been inserted back into PAR2 knock-out mice. These animals will allow us to determine the importance of
PAR2 in protection against asthma, arthritis, vascular disease and deficiencies in skin healing, as well as how
PAR2 might be a more effective protective agent in mice rather than humans. Thus, modification of the human
gene to make the protective system work as effectively as in the mouse might provide an effective therapy or
cure for diseases of the lungs, joints and skin as well as in vascular diseases.
Research achievements (from final report):
Under my leadership over the last seven years, my group has contributed substantially to a frontier field of
medical science - protease-activated receptors (PARs) and their role in inflammation. I intend to keep my
laboratory in the forefront of this field by capitalising on discoveries that PARs play central roles in anxiety,
epileptogenesis and immunological defence against allergens and autoimmune diseases.
Expected future outcomes:
My philosophy is to maintain a balance of fundamental and applied research. Research areas to date include (1)
respiratory diseases, (2) allergy and autoimmune disease and (3) central nervous system. Each of these has
significant importance globally.
Name of contact:
Tom Cocks
Email/Phone no. of contact:
thomasmc@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 208918
CIA Name: A/Pr Ann Turnley
Admin Inst: University of Melbourne
Main RFCD: Cellular Nervous System
Total funding: $451,980
Start Year: 2002
End Year: 2004
Grant Type: NHMRC Project Grants
Title of research award:
Suppressor of Cytokine Signalling-2 (SOCS2) and its role in neuronal development and functionSuppressor of
Cytokine Signalling-2 (SOCS2) and its role in neuronal development and function
Lay Description (from application):
Injury to the brain or spinal cord at present often results in permanent damage, such as paralysis, which is
largely due to a failure of neurons to regrow at the injury site. In order to overcome this, we are trying to find
ways of making new neurons grow, either from stem cells present in the nervous system or transplanted from
cells grown in tissue culture. However, little is known about how a neural stem cell decides to become a neuron
or another cell type, such as a glial cell and so we are examining factors which influence this process, which is
called differentiation. Growth factors are important mediators of this process and suppressor of cytokine
signalling (SOCS) proteins are important in determining how cells respond to growth factors. The overall aims
of this project are to determine the role that SOCS genes and in particular, SOCS2 play in neural stem cell
differentiation into neurons and glia, neuron process outgrowth and neuronal and glial injury responses in the
nervous system. This will be examined in normal cells and cells which over-express or do not express SOCS2
genes. Understanding the biology of neural growth factor responsiveness may eventually allow us to devise
therapeutic strategies for use following brain/spinal injury or disease, including generation of neurons from
stem cells.
Research achievements (from final report):
Our research has shown that a regulator of growth hormone (GH) signalling, Suppressor of Cytokine
Signalling-2 (SOCS2), is also an important regulator of nerve cell growth. Neural stem cells grown from
SOCS2 knockout mice showed a 40-50% decrease in production of neurons while increased expression of
SOCS2 promoted neuron production. An important finding of these studies was that growth hormone (GH) is
an important regulator of neuronal differentiation and that SOCS2 is required to block GH signalling to allow
neuronal production to proceed. When the brains of SOCS2 knockout mice, which do not turn off GH
signalling appropriately, were examined, they showed a 30% decrease in neuronal numbers in their cortex.
Conversely, analysis of brains of GH receptor knockout mice, which are dwarf as they are unable to respond to
GH, showed a 25% increase in neuronal numbers. SOCS2 transgenic mice, which have decreased
responsiveness to GH, showed little increase in total neuron numbers, but showed marked increases in a subset
of neurons called interneurons. While SOCS2 does not appear to play a role in neuron survival, it is also a
potent promoter of nerve process outgrowth, enhancing process length and number in neurons. This appears to
be a result of inducing activation of the epidermal growth factor (EGF) receptor and appears to be independent
of GH. SOCS2 and EGF stimulation induced similar effects on cortical neuron process outgrowth, possibly
through some of the same signalling pathways. Furthermore, analysis of GH receptor knockout and SOCS2
knockout mice showed an apparent decrease in dendritic branching in cortical neurons, while SOCS2
transgenic mice showed increased branching and an increased density of synapses. Therefore, SOCS2 is
involved in 2 important aspects of brain development and function: production of neurons and regulation of
how these neurons connect.
Expected future outcomes:
Regulation of how neurons are made and how they connect has implications for development of the brain and
regeneration after disease or injury. Understanding SOCS2 function in these processes may allow therapy
following neural damage and provide insight into development of mental health disorders that involve
abnormalities in brain wiring, such as Schizophrenia and mental retardation.
Name of contact:
Ann Turnley
NHMRC Research Achievements - SUMMARY
Email/Phone no. of contact:
turnley@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 208960
CIA Name: Prof Eleanor Mackie
Admin Inst: University of Melbourne
Main RFCD: Endocrinology
Total funding: $216,100
Start Year: 2002
End Year: 2003
Grant Type: NHMRC Project Grants
Title of research award:
The role of protease-activated receptor-2 in regulation of bone metabolismThe role of protease-activated
receptor-2 in regulation of bone metabolism
Lay Description (from application):
Many diseases of bones, such as osteoporosis and delayed fracture repair, result from the abnormal function of
bone cells. Factors regulating bone cell function are, therefore, important in maintaining a healthy skeleton, as
well as in the skeleton's response to disease. We have recently demonstrated the presence of a receptor called
PAR-2 on bone-forming cells. We have also shown that activation of PAR-2 inhibits the development of boneresorbing cells (osteoclasts) in response to hormones. We plan to investigate the mechanism of this effect, as
well as to identify how PAR-2 activation modulates other responses of bone cells to hormones. Molecules that
activate PAR-2 are present in bone in certain disease situations, but it is not known what activates PAR-2 in
bone under normal conditions. We will identify physiological activators of PAR-2 within bone.
Research achievements (from final report):
Many diseases of bones, such as osteoporosis and delayed fracture repair, result from the abnormal function of
bone cells. Factors regulating bone cell function are, therefore, important in maintaining a healthy skeleton, as
well as in the skeleton's response to disease. We have demonstrated that a receptor called PAR-2 on boneforming cells (osteoblasts) inhibits the development of bone-resorbing cells (osteoclasts) in response to
hormones. Furthermore, we have demonstrated that PAR-2 exerts this effect through inhibition of expression of
a number of factors produced by osteoblasts that are necessary for osteoclast formation. We have shown that a
number of tissue proteases that activate PAR-2 are not expressed in the bone environment, and that one
putative activator of PAR-2 is not capable of activating it. These observations add substantiallyto our
understanding of osteoclast biology, and therefore to bone biology in general.
Expected future outcomes:
The observations made in this grant have led to ongoing studies on regulation of osteoclast function by
proteases. These and our future studies are likely to help in the development of improved therapeutic
approaches to bone disease.
Name of contact:
Professor Eleanor Mackie
Email/Phone no. of contact:
ejmackie@unimelb.edu.auYes
NHMRC Research Achievements - SUMMARY
Grant ID: 209014
CIA Name: Prof Ego Seeman
Admin Inst: University of Melbourne
Main RFCD: Endocrinology
Total funding: $316,320
Start Year: 2002
End Year: 2004
Grant Type: NHMRC Project Grants
Title of research award:
Is periosteal bone formation responsible for sexual dimorphism in bone fragilityIs periosteal bone formation
responsible for sexual dimorphism in bone fragility
Lay Description (from application):
Men and women sustain fractures as they age because their bones become fragile. Women sustain fractures
more often than men. Bone thinning occurs in both sexes but it is usually believed that this thinning or loss of
bone is greater in women than men. We have evidence to suggest that this may not be correct. In fact, it is
likely that men and women lose a similar amount of bone, about half what they started with, but during ageing,
men lay down more bone on the outside surface of the bone than women compensating for the similar amount
lost on the inside of the bone. We also have evidence to suggest than men and women who get spine fractures
do so because the process of laying down bone may fail to occur normally. We will study these processes of
bone loss inside the bone and bone gain outside the bone to try to better understand why bones become weak.
We will measure the bone size and its density in healthy men and women and patients with fractures to
determine how the increasing size of the bone produced by laying down bone on its outside helps to keep it
strong and to preserve the bone that would otherwise be lost if it didn't occur or if a disease developed that
might reduce the compensatory
Research achievements (from final report):
We studied 1013 healthy subjects (327 men, 686 women), 125 patients with spine fractures (36 men and 89
women), and 307 patients with hip fractures (127 men, 180 women). We made the following observations:, At
the spine (i) reduced bone fromation on the outer surfaces (periosteum) of the verebral body during growth or
agening, may be in part responsible of verebral fragility and spinal fractures. (ii) The biomechanical index fracture risk indes (FRI) - is not a better predictor of spinal fractures than bone density. In addition, we found
that women, not men, with vertebral fractures may come from a population with short stature. The difference
between arm span and standing or sitting height cannot be sued to predict vertebral fracture risk., At the hip, we
reported that, differences in the geomentry between men and women were confined to further displacement of
the cortex (the wall of the bone) from neutral axis in young men compared to young women explaining why
men bones are stronger. Ageing amp;ified these differences shifting the cortex even further from the neutral
axis and maintaining the bending strength of the bone in men, but not in women. This at least partly explained
the lower fracture rate in men compared to women. Also, we observed that compared to their peers women and
men with hip have reduced cortical thickness. Women who fracture have larger bones. Where as men who
fracture have smaller bones.
Expected future outcomes:
target the periosteum as a very effective way of maintaining bone strength and reducing the burden of fracture.,
It is likely that bone size, independently of bone density, could be used in the future to predict fracture. We
plan to test this hypothesis emanating from this grant.
Name of contact:
Ego Seeman
Email/Phone no. of contact:
egos@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 209113
CIA Name: Prof Wayne Morrison
Admin Inst: University of Melbourne
Main RFCD: Surgery
Total funding: $226,320
Start Year: 2002
End Year: 2004
Grant Type: NHMRC Project Grants
Title of research award:
THE ROLE OF RESIDENT MAST CELLS IN ISCHAEMIA-REPERFUSION INJURY OF SKELETAL
MUSCLE.THE ROLE OF RESIDENT MAST CELLS IN ISCHAEMIA-REPERFUSION INJURY OF
SKELETAL MUSCLE.
Lay Description (from application):
NHMRC 209113 LAY DESCRIPTION Ischaemia reperfusion injury occurs in skeletal muscle when the
blood/oxygen supply is cut off (ischaemia) and later restored (reperfusion). If the duration of ischaemia is
short some of the muscle survives. However, when blood flow and oxygen are restored the muscle is subjected
to more injury, which is thought to be caused by oxygen and/or white blood cells. This type of injury occurs in
muscle which has been crushed, limbs that have been broken or traumatized, in replantation of amputated parts,
in transplantation, after some surgical procedures and after microsurgical transfer of muscle. Once established
there is no effective treatment. Our experiments show that a particular cell, the mast cell, and a particular
molecule, nitric oxide, are involved in causing ischaemia reperfusion injury. However, the extent of their
involvement is unknown. In this proposal we will investigate the effect of replacing mast cells into muscles, in
a unique variety of mice which normally don t contain mast cells and are resistant to ischaemia reperfusion
injury. In one group of mice we will put back normal mast cells and in a second group of mice we will put back
mast cells that cannot produce the nitric oxide molecule. These experiments will determine, unambiguously,
the extent of involvement of mast cells and mast cell-derived nitric oxide. In the second part of this proposal
will carry out a time course study, using pharmacologically induced mast cell degranulation, to determine
when the mast cells become injurious to skeletal muscle. These experiments will identify the period during
which mast cell behaviour can be modulated in order to protect the muscle from ischaemia reperfusion injury.
Determination of the role of mast cells, and an understanding of the timing during which they become injurious
would provide a logical basis for optimizing drug therapy in clinical applications of these findings.
Research achievements (from final report):
Ischaemia reperfusion (IR) injury occurs in skeletal muscle when the blood/oxygen supply is cut off
(ischaemia) and later restored (reperfusion). If the duration of ischaemia is short some of the muscle survives.
However, when blood flow and oxygen are restored the muscle is subjected to further injury, which is thought
to be cause by oxygen and/or white blood cells. This type of injury occurs in muscle which has been crushed,
limbs that have been broken or traumatized, in replantation of amutated parts, after some surgical procedures
and after microsurgical transfer of muscle. Once established there is no effective treatment. Experiments from
this study show that a particular cell, the mast cell, plays a pivotal role in causing ischaemia reperfusion injury.
By using mice deplete in mast cells, we are able to reduce muscle death by more than 50%. Furthermore, by
replacing the mast cells back into the mast cell deplete mice (a technique known as re-engraftment), we were
able to confirm that mast cells contribute to the majority of muscle injury during IR. This work was presented
at an international conference in USA and a grant was awarded 1 of 4 scholarship, based on the quality of the
research. The results from this study have broader implications for the prevention/treatment of acute
inflammatory reactions associated with IR injury in other scenarios such as heart bypass, organ transplantation
and heart disease.
Expected future outcomes:
Based on the results from this study, this has for the first time identified a clear target for drug therapy in IR
injury of skeletal muscle. It is likely to be relevant for prevention of injury in other ischaemic diseases, in
particular cardiac ischaemia (heart attacks).
Name of contact:
Pfor Wayne Morrison
NHMRC Research Achievements - SUMMARY
Email/Phone no. of contact:
Wayne.Morrison@svhm.org.au
NHMRC Research Achievements - SUMMARY
Grant ID: 209168
Start Year: 2002
CIA Name: Dr Kay Crossley
End Year: 2006
Admin Inst: University of Melbourne
Grant Type: Early Career Fellowships (Australia)
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $138,088
Title of research award:
Factors affecting motor control and loading of the patellofemoral jointFactors affecting motor control and
loading of the patellofemoral joint
Lay Description (from application):
Not Available
Research achievements (from final report):
Joint swelling and pain are hallmarks of many knee conditions, particularly knee osteoarthritis in adults and the
elderly and patellofemoral pain in adolescents or adults. Such conditions are also frequently associated with
altered thigh muscle function, including weakness, inhibition and altered activation, which occur in the absence
of damage to the muscle itself. It is not known whethe the pain or swelling directly influences this thigh muscle
function. This research was a series of studies, primarily conducted in healthy people. These studies involved
the injection of pain provoking substance into the knee and evaluating the effects of the resulting knee pain on
thigh muscle function. The results of this study demonstrated that the induced knee pain resulted in alterations
in the amount and timing of thigh muscle activity, and the way that people walk. The other study involved
injecting fluid into the knee to mimic knee swelling. Similar to the knee pain study, this artificial swelling
resulted in alterations in the amount and timing of thigh muscle activity in the during functional tasks. The
results of these study provide compelling evidence that knee pain and swelling have considerable effects on
thigh muscle function and must be addressed in order to attain successful rehabilitation of painful knee
conditions
Expected future outcomes:
N/A
Name of contact:
Kay Crossley
Email/Phone no. of contact:
k.crossley@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 251535
CIA Name: Dr Pritinder Kaur
Admin Inst: University of Melbourne
Main RFCD: Dermatology
Total funding: $391,763
Start Year: 2003
End Year: 2005
Grant Type: NHMRC Project Grants
Title of research award:
Microenvironmental regulation of the tissue regenerative capacity of keratinocyte stem cells and their
progeny.Microenvironmental regulation of the tissue regenerative capacity of keratinocyte stem cells and their
progeny.
Lay Description (from application):
The protective outer layers of the skin known as the epidermis belongs to a group of tissues in the body that are
turning over at a rapid rate. The majority ofepidermal cells have a lifespan of just 2-3 weeks, and are shed as
mature cells from the skin's surface. These cells are replaced by continuous cell regeneration which is
dependent on growth factors and adhesive molecules (and other signals). It has recently come to light that the
connective tissue of the skin i.e. the dermis, which lies directly below the epidermal cells has a critical role in
providing some of these factors required for their growth and maturation. Indeed, it is becoming increasingly
clear that the epidermal and dermal cells co-operate to regulate epidermal proliferation and maturation. Recent
work from our laboratory has shown that a newly recognised adhesive protein laminin-10 may be produced as
the result of such co-operation and that it stimulates the growth of both normal and tumour epidermal cells.
We have also recently identified an interesting subset of dermal cells that may have a role in promoting the
growth of the epidermal cells. Thus, the aims of the proposed stuides are to investigate the role of laminin-10
and this specific dermal cell subset in epidermal proliferation and maturation. These studies may also provide
an insight into the role of these factors in skin cancers.
Research achievements (from final report):
This work revealed that stem cells of the skin (particularly the outermost layer known as the epidermis) are
dependent on growth factors and proteins supplied by adjacent cells found in their environment i.e. dermal cells
in order to grow and repair skin tissue defects. Interestingly, the ability to repair wounds is not restricted to
stem cells alone as previously thought but can be conferred upon the maturing progeny of the stem cells when
the appropriate environmental signals are provided. Thus in laboratory models of skin tissue regeneration, skin
repair could be obtained by adding exogenous proteins normally found in the skin to non-stem cells. Particular
subsets of cells found in the dermis have also been identified as important populations in promoting tissue
repair from non-stem cells. The significance of these findings is that it may be possible to use non-stem cells
together with stem cells to provide transplantable cells onto patients suffering from severe skin deficits such as
burns. Specific skin proteins may also be utilised to expand skin cells from patient's faster before
transplantation avoiding delays in getting skin grafts and reducing the risk of infection and thus survival of the
patient.
Expected future outcomes:
The dermal cells identified in this study as being important for tissue repair need to be studied further to
understand the nature of signals (i.e. growth factors/proteins) they provide to stimulate skin repair. These
molecules could then be used to devise therapies for faster skin regeneration for patients.
Name of contact:
Pritinder Kaur
Email/Phone no. of contact:
pritinder.kaur@petermac.org
NHMRC Research Achievements - SUMMARY
Grant ID: 251575
CIA Name: Prof Eleanor Mackie
Admin Inst: University of Melbourne
Main RFCD: Endocrinology
Total funding: $120,775
Start Year: 2003
End Year: 2003
Grant Type: NHMRC Project Grants
Title of research award:
Cellular responses to thrombin in skeletal pathologyCellular responses to thrombin in skeletal pathology
Lay Description (from application):
Many diseases of bones, such as osteoporosis and delayed fracture repair, result from the abnormal function of
bone cells. Factors regulating bone cell function are, therefore, important in maintaining a healthy skeleton, as
well as in the skeleton's response to disease. The enzyme thrombin is involved in blood coagulation but also
causes bone cells to alter their behaviour. Thrombin stimulates proliferation of bone-forming cells and protects
them from premature death. Thrombin also stimulates the breakdown of bone. We will investigate how
thrombin's effects on bone cell behaviour influence the course of bone healing. We will also determine how
thrombin stimulates bone breakdown and increases survival of bone-forming cells. This study will contribute
to the understanding of how bone cells function in health and disease.
Research achievements (from final report):
Many diseases of bones, such as osteoporosis and delayed fracture repair, result from the abnormal function of
bone cells. Factors regulating bone cell function are, therefore, important in maintaining a healthy skeleton, as
well as in the skeleton's response to disease. The enzyme thrombin is involved in blood coagulation but also
causes bone cells to alter their behaviour. In this project we have demonstrated that the early stages of bone
healing occur abnormally in the absence of the major thrombin receptor found in bone (PAR-1). We have
found that thrombin stimulates formation of osteoclasts (bone-resorbing cells). We have also identified a
signalling pathway through which thrombin prevents the death of osteoblasts (bone-forming cells). These
observations add substantiallyto our understanding of the biology of bone growth, maintenance and repair.
Expected future outcomes:
The observations made in this grant have led to ongoing studies on regulation of osteoclast function by
proteases. These and our future studies are likely to help in the development of improved therapeutic
approaches to bone disease.
Name of contact:
Professor Eleanor Mackie
Email/Phone no. of contact:
ejmackie@unimelb.edu.auYes
NHMRC Research Achievements - SUMMARY
Grant ID: 251638
CIA Name: A/Pr Mark Kotowicz
Admin Inst: University of Melbourne
Main RFCD: Endocrinology
Total funding: $428,225
Start Year: 2003
End Year: 2005
Grant Type: NHMRC Project Grants
Title of research award:
BONE SIZE AND BONE TURNOVER: RELATIONSHIP TO FRACTURE RISK OVER TEN
YEARSBONE SIZE AND BONE TURNOVER: RELATIONSHIP TO FRACTURE RISK OVER TEN
YEARS
Lay Description (from application):
The occurrence of fracture in the ageing population is a major public health problem because these fractures
are responsible for considerable morbidity and mortality. Of women reaching 90 years of age, one third will
fracture their hip and overall, one in every six women will sustain an osteoporotic fracture in her lifetime. The
direct cost to the community is unknown but estimated, conservatively, at 175 million dollars annually. Most
of this is likely to be the result of hip fractures which occupy an estimated 400,000 bed-days annually. This
bed occupancy is fourth next to mental illness, cardiac disease and cancer. The Geelong Osteoporosis Study is
a large population-based epidemiological study currently under way to evaluate the major risk factors for
fracture in women . This present study which will be an extension of the study to date, will provide in total, 810 years of data concerning the processes that result in increased bone fragility and fracture.
Research achievements (from final report):
The present study is an extension of the Geelong Osteoporosis Study, a large population-based epidemiological
study designed to evaluate major fracture risk factors in women, and provides up to 10 years of data about the
development of bone fragility and fracture. We have shown that hip fracture patients have thinning of the outer
shell of the thigh bone that likely compromises bone strength and that there is a compensatory increase in the
diameter of the bone. Additional information about the biomechanical implications of these structural changes
will become available when Hip Structure Analysis of all bone densitometry scans is complete. We have
developed a clinically useful fracture risk (FRISK) score that predicts fracture by combining information from
bone densitometry, previous fracture and falls history. The FRISK score predicts 75% of fractures over a 2 year
period. Systemic inflammation, as assessed by measurement of high sensitive C-reactive protein (hsCRP),
predicts fracture risk over and above information provided by bone densitometry. The role of vitamin D, the
influence of drug exposures, the nervous system, genetic factors, oxidative stress and depression in bone
fragility have been reported. We have demonstrated that the population burden of fracture comes from the large
number of individuals with a modest reduction in bone mass rather than the relatively small number of highrisk individuals with osteoporosis. Reference ranges for bone densitometry have been established, the health
impact of fragility fracture and cost benefit analyses of treating women with osteopenia and osteoporosis have
been published.
Expected future outcomes:
Development of an updated FRISK score incorporating bone turnover markers and hsCRP, pursuit of a
common aetiology for osteoporosis and cardiovascular (CVD) disease based on predictive value of hsCRP in
both disorders and evidence of systemic inflammation in CVD, evaluation of osteoporosis in men using
expertise gain from this study (NHMRC Project 299831)
Name of contact:
Assoc Prof Mark Kotowicz
Email/Phone no. of contact:
markk@BarwonHealth.org.au
NHMRC Research Achievements - SUMMARY
Grant ID: 251682
CIA Name: Prof Geoffrey Nicholson
Admin Inst: University of Melbourne
Main RFCD: Primary Health Care
Total funding: $305,750
Start Year: 2003
End Year: 2007
Grant Type: NHMRC Project Grants
Title of research award:
Primary care prevention of falls and fractures in the elderly by annual vitamin D supplementationPrimary care
prevention of falls and fractures in the elderly by annual vitamin D supplementation
Lay Description (from application):
While Australia has one of the highest rates of skin cancer, many of us are not receiving enough sun exposure
to adequately maintain necessary blood levels of vitamin D. For years it was assumed that vitamin D
deficiency was rarely seen in Australia where sunlight abounds for most of the year. Although few foods are
high in vitamin D, it was thought that only certain cultural groups where women are always veiled in public,
very dark-skinned people and the housebound elderly, were at risk of vitamin D deficiency. Lower vitamin D
levels following wintertime have now been reported in many populations including those living near the
Mediterranean and in Geelong, Victoria. Vitamin D insufficiency is associated with an increased risk of
falling through increased body sway and muscle weakness. Low levels of the vitamin also encourage the
removal of calcium from bones and will predispose to bone fracture for two reasons - increased likelihood of
falling and increased bone fragility and osteoporosis. Osteoporotic fractures are amongst the most important
causes of ill-health among elderly people, causing an estimated 65,000 fractures in 2000-01. If nothing is
done, fracture rates are estimated to increase from one every 8.1 minutes in 2001, to one every 3.7 minutes in
2021. Falls among the elderly are also a major health with about a third of people over 70years falling at least
once every year. Almost 90% of all hip fractures result from the impact of a fall. This project will trial an
annual dose of vitamin D to the elderly at high risk of vitamin D deficiency, falls and fractures. Fifteen
hundred women will be supplemented with either vitamin D or a placebo "dummy" pill at the beginning of
winter for five years. The supplementation will take place through their local doctor and researchers will
expect to see fewer falls and bone fractures occurring in those receiving vitamin D than in the group receiving
the placebo.
Research achievements (from final report):
The Vital D study successfully recruited 2,317 women aged at least 70 years and who were assessed as at a
higher risk of fragility fracture or osteoporosis. Although the initial NHMRC 5-year grant funding has finished,
the study has been awarded further NHMRC funding to extend the project's outcomes. All participants will
complete the study during 2008. The findings have been extended to investigate not only the prevention of falls
and fractures, as originally planned but also to investigate if vitamin D supplementation improves mental health
in the elderly and if vitamin D supplementation over a number of years reduces the overall use and cost of
medical and hospital services. Since commencing this project in 2003 the many potential benefits of an
adequate to high vitamin D status has received much scientific attention. The project's pragmatic design
continues to have much appeal. The concept of a once-a-year dose of vitamin D tablets holds promise as
several international studies on vitamin D supplementation have reported low compliance of the study tablets
when participants were required to take calcium and vitamin D tablets on a daily basis. The results of these
other studies generally show that vitamin D prevents falls and fractures when targeted to participants likely to
have a low vitamin D status. Not surprisingly when the analysis of results includes both those participants who
took the daily supplementation and those participants who were asked to but didn't take the tablets on a regular
basis, the evidence that vitamin D prevents falls and fractures is weaker. The results of other studies has also
shown that the dose of vitamin D needs to be sufficiently large to increase the levels of the vitamin in the blood
and to show benefits to bone health. Participants in our study -Vital D randomised to vitamin D have been
given an annual dose of 500,000 IU of vitamin D3 (cholecalciferol). This dose continues to be regarded as
sufficiently high.
Expected future outcomes:
NHMRC Research Achievements - SUMMARY
The main analysis comparing falls and fractures in participants taking the vitamin D tablets with those taking
placebo will commence later this year when all participants have finished the study and the research team are
no longer 'blinded' as to their active or placebo status.
Name of contact:
Dr Kerrie Sanders
Email/Phone no. of contact:
kerrie@barwonhealth.org.au
NHMRC Research Achievements - SUMMARY
Grant ID: 299831
CIA Name: Prof Geoffrey Nicholson
Admin Inst: University of Melbourne
Main RFCD: Endocrinology
Total funding: $432,645
Start Year: 2004
End Year: 2006
Grant Type: NHMRC Project Grants
Title of research award:
MALE OSTEOPOROSIS: A POPULATION-BASED STUDY IN GEELONGMALE OSTEOPOROSIS: A
POPULATION-BASED STUDY IN GEELONG
Lay Description (from application):
Osteoporosis is a term used to indicate that bones have become thin and fragile. During the ageing process
bone fragility increases and fractures occur more easily and more often. Fractures may also occur during
normal daily activities, with fractures of the spine, forearm and hip being common. However, many other sites
may fracture. This is a serious problem because fractures cause pain, disability and, sometimes, death.
Although previously overshadowed by its effect in women, osteoporosis is increasingly being recognised in
men. In Australia, 39% of all fractures occur in men and prognosis for fracture in men is worse than in women.
A consequence of increasing male longevity is that osteoporosis will affect a growing number of Australian
men. It is anticipated that between 1996 and 2051, the number of men with fracture will double, with a 4-fold
increase in the number of male hip fractures. Unless the problem of osteoporosis in men is addressed and
effective interventions are implemented, the substantial health burden imposed by age-related fractures will
continue to escalate. In this case-control study of fracture risk in men, men with fractures (cases) will be
identified prospectively for 3 years from radiological reports. Controls will be selected concurrently, at
random from electoral rolls. Anticipated number of cases and controls are 800 and 1400, respectively. Cases
and controls will be characterised for risk factors for fracture: bone density and bone geometry will be
measured, serum samples collected, and diet, lifestyle and medical history documented by questionnaire. The
advantage of this type of data is that information from patients with fracture will be used to tell us about the
risk of fracture in healthy, unaffected men and about the characteristics of the Australian male population at
risk for fracture. The information can be used in decision making for the individual and in policy making for
the whole population.
Research achievements (from final report):
This large population-based epidemiological study enrolled 1,540 men (aged 20-97 years) to evaluate major
fracture risk factors. Assessments included bone mineral density (BMD), demographic, anthropometric and
clinical data; diet; osteoporosis risk factors; medical, falls and fracture history; drug exposures; muscle strength
and gait; and fasting blood samples for biochemical, hormonal and genetic analysis. , BMD reference ranges
will be made available for use on all densitometers across Australia, once finalised. Using bone densitometry,
measurement of vertebral height identified alterations in vertebral dimensions that define fracture. We have
determined age distribution of newly recognised vertebral fractures for ambulatory men and shown that these
fractures remain largely undiagnosed, are associated with poor quality of life, compromised mobility, balance
and physical activity. Relatively few high trauma fractures occur among elderly men whereas they predominate
in younger men., Among men with depression, BMD is reduced, suggesting that depression may be an
osteoporosis risk factor. Metabolic syndrome, a combination of features realted to obesity associated with
increased risk cardiovascular was identified in nearly 1/3 of middle-aged and elderly men. These men have
increased BMD, possibly related to skeletal loading. We have also reported that men with prostate cancer have
reduced BMD. Magnetic resonance imaging was explored as a promising technique for identifying structural
parameters of bone associated with ageing and bone fragility.
Expected future outcomes:
Development of a clinically useful fracture risk score incorporating multi-site bone mineral density, clinical
risk factors, biomarkers and structural parameters of bone, investigation of a common aetiology for
osteoporosis and depression based on predictive value of markers of inflammation and inflammatory cytokines,
further evaluation of the metabolic syndrome in men.
NHMRC Research Achievements - SUMMARY
Name of contact:
Assoc Prof Julie Pasco
Email/Phone no. of contact:
juliep@barwonhealth.org.au
NHMRC Research Achievements - SUMMARY
Grant ID: 299840
Start Year: 2004
CIA Name: Prof Kim Bennell
End Year: 2006
Admin Inst: University of Melbourne
Grant Type: NHMRC Project Grants
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $384,675
Title of research award:
Efficacy and cost-effectiveness of physiotherapy for chronic rotator cuff pathologyEfficacy and costeffectiveness of physiotherapy for chronic rotator cuff pathology
Lay Description (from application):
Shoulder disorders are common, being third only to back and neck complaints as musculoskeletal reasons for
medical consultation and accounting for 10% of all physiotherapy referrals. The painful shoulder affects up to
2-5% of the general population, being more common in middle to older age. One of the most common shoulder
disorders is chronic rotator cuff pathology. This causes significant pain and disability that restricts activities of
daily living as well as work, sleep and leisure. Forty percent of sufferers will continue to have symptoms
beyond 3 years and 15% will have persistent disability which may require surgical intervention. Because this
disorder is prevalent, it imposes a considerable burden on the Australian health care system. Physiotherapy is a
common conservative treatment option but its efficacy has not been well established. A recent Cochrane review
of the literature revealed several problems with many of the existing studies: (i) the populations have included
a mix of shoulder diagnostic categories; (ii) the research designs have major flaws and (iii) a single
physiotherapy modality has been evaluated rather than a combined program as is current clinical practice.
Thus, this novel research project involving 200 participants will answer important questions about the efficacy
of a physiotherapy program for chronic rotator cuff pathology and whether benefits can be maintained. In
addition it will determine whether the costs of physiotherapy represent good value for money which is
important in today's economic climate. The results of this project can be easily and immediately translated into
clinical practice as recommendations can be made about the usefulness of physiotherapy for this patient
population. The results will be of major benefit not just to the physiotherapy profession but to the medical
profession who must justify patient referral to physiotherapy and to funding and compensable bodies.
Research achievements (from final report):
This study was a clinical trial that investigated the efficacy and cost effectiveness of a 10 week physiotherapy
program for chronic rotator cuff pathology of the shoulder. One hundred and twenty people with the condition
were recruited from medical practices and from the general public by print and radio media. Participants were
randomised into a physiotherapy or a placebo group. Both groups attended a physiotherapist for 10 sessions
over 10 weeks. The physiotherapy program was aimed at improving strength, range of motion, reducing pain
and improving shoulder function. The placebo group received inactive treatment. The groups were assessed at
baseline, after 10 weeks and at a 22 week followup with the main outcome measure being change in pain and
disability. This study provides information that assists in evidence based recommendations for the management
of this chronic shoulder condition. Specifically it provides evidence about the role of a physiotherapy program
for chronic rotator cuff pathology.
Expected future outcomes:
It is anticipated that this study will be used to inform clinical guidelines relating to the management of chronic
rotator cuff pathology. The results will also be used by physiotherapy clinicians to assist them to better manage
their patients with this shoulder condition. It will also be used by other practitioners who refer their patients for
physiotherapy.
Name of contact:
Kim Bennell
Email/Phone no. of contact:
k.bennell@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 300054
CIA Name: A/Pr Jane Pirkis
Admin Inst: University of Melbourne
Main RFCD: Mental Health
Total funding: $444,500
Start Year: 2004
End Year: 2008
Grant Type: Career Development Fellowships
Title of research award:
Preventing suicidal behaviours: Ecological studies of systemic protective factorsPreventing suicidal
behaviours: Ecological studies of systemic protective factors
Lay Description (from application):
Not Available
Research achievements (from final report):
Most international research efforts in suicide prevention have focused on exploring the rates of and risk factors
for suicidal behaviour. My program of work considered some of the factors that might be protective against
suicide at a range of levels (individual, ecological, intervention/service-based, systemic). My work has
influenced policy and practice in a number of ways, including helping to shape national and international
guidelines on media reporting of suicide, and influencing the nature of several national mental health and
suicide prevention initiatives.
Expected future outcomes:
I would anticipate that my work will continue to have an impact on policy and practice in a similar manner.
Name of contact:
Jane Pirkis
Email/Phone no. of contact:
j.pirkis@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 350227
CIA Name: A/Pr Ann Turnley
Admin Inst: University of Melbourne
Main RFCD: Central Nervous System
Total funding: $486,000
Start Year: 2005
End Year: 2007
Grant Type: NHMRC Project Grants
Title of research award:
Signalling mechanisms regulating neurogenesis and neurite outgrowthSignalling mechanisms regulating
neurogenesis and neurite outgrowth
Lay Description (from application):
Injury and diseases of the central nervous system (CNS), such as traumatic injury, stroke, Parkinson's,
Huntington's and Alzheimer's disease, affect a substantial number of Australians each year and often have
long-term consequences for sufferers and their families. This is primarily due to a lack of robust repair of the
damage and a paucity of therapeutic strategies available for treatment. However, although many hurdles are yet
to be faced, there is a substantial body of evidence that has emerged in recent years, that has led to the view
that repair of the central nervous system following injury of disease may indeed be a possibility. Effective
neural repair is likely to require a multi-factorial approach, including blockage of neuronal death, replacement
of lost neurons by neural stem cells, and regulation of appropriate subsequent neurite outgrowth and formation
of correct connections. We have shown that a regulator of cytokine signaling, SOCS2, promotes neuronal
differentiation and neurite outgrowth. This project aims to continue our investigations of the role of SOCS2
and interacting factors in regulating neuronal differentiation as well as substantially expanding our
investigations into the role of SOCS2 in regulating neurite outgrowth, using both in vitro and in vivo models.
An understanding of the mechanisms involved in these processes may allow us to derive therapies for the
repair of the nervous system after injury or disease.
Research achievements (from final report):
We examined factors that have to potential to promote production of new neurons from neural stem cells and
enahnce their survival and integration into the nervous system. In culture We have found that both the
inflammatory regulators dexamethasone and IFN inhibited neural stem cell proliferation and enhanced
neuronal differentiation, while Growth Hormone accelerated neuronal differentiation and increased neural stem
cell proliferation. We also examined production of new nerve cells in the adult mouse brain following
administration of Erythropoietin (Epo) and in the presence of altered growth hormone signalling. Epo
transiently enhanced production of new neurons but did not promote long term survival. Epo also regualted
growth of these neurons in cell culture. Mice which expressed a regulator of growth hormone signalling,
SOCS2 transgenic mice, showed normal short term proliferation of neural precursor cells but enhanced long
term survival of new neurons in the brain. SOCS2 transgenic mice were also less anxious than normal mice and
had enahnced memory. We have also found that SOCS2 intereacts with other signalling pathways not related to
growth hormone, in particular the neurotrophin growth factor family, which may have important therapeutic
consequences. Administration of Epo or regualtion of SOCS2 or Growth Hormone may improve recovery
following nervous system injury.
Expected future outcomes:
Further understanding of the role SOCS2 plays in regulating factors other than growth hormone. Future studies
will examine the role of SOCS2 and related factors in regulating recovery from nervous system injury.
Name of contact:
Ann Turnley
Email/Phone no. of contact:
turnley@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 350297
Start Year: 2005
CIA Name: Prof Kim Bennell
End Year: 2008
Admin Inst: University of Melbourne
Grant Type: NHMRC Project Grants
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $480,850
Title of research award:
Effects of laterally wedged insoles on symptoms and disease progression in knee osteoarthritisEffects of
laterally wedged insoles on symptoms and disease progression in knee osteoarthritis
Lay Description (from application):
Knee arthritis is a painful, disabling, costly condition particularly affecting the elderly. As there is presently no
cure for knee arthritis, strategies that slow progression of the disease will reduce the personal and societal
burden of arthritis. Most research has focussed on drug therapies, which are effective in reducing pain and
disability but have side effects and are expensive. Insoles worn inside the shoes are a simple, cheap, selfadministered intervention with the potential to slow disease progression in certain patients, in addition to
managing symptoms. However, to date there has been little quality research investigating the effectiveness of
insoles in knee arthritis. This study aims to see whether 12 months of wearing insoles can lead to
improvements in knee pain and function and slow disease progression in 200 people with knee arthritis. It will
use state-of-the-art technology, magnetic resonance imaging, to measure changes in the amount of knee
cartilage. This research is timely and the findings will be of major significance as there is increasing worldwide attention on slowing progression of knee arthritis. Insoles are one of the few non-drug therapies with the
potential to influence both symptoms and disease progression. If the results show that insoles are beneficial,
then this research will: 1. Better inform clinical guidelines to firmly recommend insoles to manage knee
arthritis 2. Provide the basis for developing education strategies for health care practitioners and patients about
the benefits of insoles 3. Provide the impetus to make insoles more readily available directly to patients 4.
Ultimately lead to better patient outcomes
Research achievements (from final report):
The majority of clinical guidelines recommend lateral wedge shoe insoles for medial knee osteoarthritis (OA),
despite limited and equivocal evidence of efficacy. The primary aim of this randomised controlled trial was to
assess the efficacy of lateral wedge insoles for improving symptoms and slowing structural disease progression
compared with control insoles in medial knee OA. 200 people with knee OA and aged 50 or more were
recruited from the community in Melbourne, Australia. Participants wore either full-length 5 degree lateral
wedged insoles or flat control insoles inside their shoes daily for 12 months. Measurements were taken at
baseline and 12 months later and included measures of pain, physical function, quality of life and knee joint
structure (from magnetic resonance imaging). Ninety percent of participants completed the study. The results
showed that there were no significant differences between the lateral wedge insole and the control insole
groups for any of the measures. This suggests that lateral wedge insoles worn for 12 months provide no
symptomatic or structural benefits compared to a flat control insole.
Expected future outcomes:
This study does not support the use of lateral wedge insoles in the management of people with medial knee
osteoarthritis. This is likely to alter future recommendations of clinical guidelines.
Name of contact:
Kim Bennell
Email/Phone no. of contact:
k.bennell@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 350426
CIA Name: A/Pr Paul Whitington
Admin Inst: University of Melbourne
Main RFCD: Neurogenetics
Total funding: $251,325
Start Year: 2005
End Year: 2007
Grant Type: NHMRC Project Grants
Title of research award:
The molecular basis for target selection in the central nervous system by sensory axonsThe molecular basis for
target selection in the central nervous system by sensory axons
Lay Description (from application):
The normal function of the brain depends upon the specific connections that nerve cells make with each other.
These connections are set up in the developing embryo when nerve cells send out long processes - axons which grow towards their synaptic targets. How axons select their correct targets from amongst the millions of
alternatives in the developing brain is unknown. A better understanding of this problem will help us develop
therapies to assist regenerating axons re-establish correct connections following injury to the brain or spinal
cord. We propose to use a simple model system, the embryo of the fruitfly Drosophila, to find molecules that
are involved in this process of neuron target recognition - ' axon targeting' molecules - and to study how they
work. Drosophila can be genetically manipulated in ways not possible in higher animals. Furthermore the
simplicity of its nervous system means that we can determine the connections of individual nerve cells with a
high degree of precision. In the first part of our project, we will examine Drosophila embryos that carry
mutations in genes suspected to code for targeting molecules. We will stain individual sensory nerve cells in
these embryos with dyes to reveal the anatomy of their axons in the brain. If sensory axons terminate
abnormally in the brain of a given mutant, the affected gene is likely to code for an axon targeting molecule. In
the second part of the study, we will investigate the functions of candidate axon targeting molecules using two
approaches. Firstly, we will seek to determine whether the molecule acts in the sensory axons or in their target
cells. Secondly, we will use time-lapse microscopy to study how the homing behaviour of the sensory axons is
affected in mutant embryos. The results of these studies will lead us closer to an answer to the question: "How
do axons recognise their specific target cells in the brain?"
Research achievements (from final report):
The normal function of the brain depends upon the specific connections that nerve cells make with other nerve
cells. These connections are set up in the developing embryo when nerve cells send out long processes - axons
- which grow towards their targets. How axons select their correct targets from amongst the millions of
alternatives in the developing brain is largely unknown. A better understanding of this phenomenon of "axon
targeting" will help us develop therapies to assist regenerating axons re-establish correct connections following
injury to the brain or spinal cord. We are using a simple model system, the embryo of the vinegar fly
Drosophila, to identify molecules that are involved in axon targeting and to study how they work. We have
discovered that a well-known molecule, Epidermal Growth Factor Receptor (EGFR), is involved in this
process. This protein plays a role in a host of developmental processes in which cells are required to respond to
signals in their environment, but was not previously known to regulate axon growth. Our discovery will now
enable us to work out how activation of this molecule triggers changes in nerve cells that cause their axons to
grow in the right direction. This knowledge could be as relevant to cancer research as to neuroscience, because
abnormal EGFR activity also leads to tumour formation in ways that are as yet poorly understood.
Expected future outcomes:
The knowledge gained from this study will in the future help us find ways to promote recovery of function in
parts of the brain that are damaged by injury, disease or the aging process.
Name of contact:
Dr Paul Whitington
Email/Phone no. of contact:
p.whitington@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 350483
CIA Name: Dr Glenn McConell
Admin Inst: University of Melbourne
Main RFCD: Exercise Physiology
Total funding: $340,750
Start Year: 2005
End Year: 2007
Grant Type: NHMRC Project Grants
Title of research award:
IS NITRIC OXIDE A CENTRAL REGULATOR OF EXERCISE-INDUCED SKELETAL MUSCLE
MITOCHONDRIAL BIOGENESIS?IS NITRIC OXIDE A CENTRAL REGULATOR OF EXERCISEINDUCED SKELETAL MUSCLE MITOCHONDRIAL BIOGENESIS?
Lay Description (from application):
Mitochondria are the energy producing parts of the cell and are the major controllers of metabolism. There is
now good evidence that reduced muscle mitochondrial size contributes to diabetes. Exercise is good for
diabetics due partly to increasing muscle mitochondrial production (mitochondrial biogenesis). Unfortunately,
little is known about the mechanisms involved in increased muscle mitochondrial biogenesis following
exercise. It has been shown recently that nitric oxide (NO), a gas made by muscle during exercise, plays a role
in mitochondrial biogenesis in fat cells. This project will determine whether NO is a central regulator of
exercise-induced mitochondrial biogenesis in skeletal muscle. If we find that NO increases mitochondrial
biogenesis in muscle, drugs designed to mimic these exercise effects may prevent or improve diabetes. We
will firstly establish if specific drug treatments that alter NO levels in muscle cells grown in culture alter
mitochondrial biogenesis. These results will help us to clarify the role of NO in mitochondrial biogenesis.
However, it is difficult to directly examine the effects of exercise in cultured cells. Therefore, further studies
will then use real life models such as rodents that have been exercised to examine the role of NO and exercise
on mitochondrial biogenesis. We will feed a drug to decrease NO levels in normal rats; and use mice,
genetically altered to be lacking in NO to determine if these treatments decrease mitochondrial biogenesis that
is normally seen following endurance exercise. Furthermore, since defects in mitochondrial biogenesis have
such an important impact on diabetic humans, we will use humans to examine if differences in NO levels in
skeletal muscle among type 2 diabetics or endurance-trained athletes correlate with mitochondrial biogenesis.
Finally, we will infuse a drug into type 2 diabetics that increases NO in muscle to determine if it also increases
mitochondrial biogenesis.
Research achievements (from final report):
Mitochondria are the energy procing oragns of the cell. Defective small skeletal muscle mitochondria are now
recognised as a major component of the metabolic abnormalities of diabetes. Exercise increases mitochondrial
volume and improves mitochondrial function (mitochondrial biogenesis). Many research groups are attempting
to determine how exercise increases mitochondrial biogenesis and thereby prevents or improves diabetes.
There are large gaps in our current knowledge. Prior to commencing our grant funding a paper presented
convincing evidence that nitric oxide (NO) regulates mitochondrial biogenesis in fat cells. As skeletal muscle
NO production increases during exercise, NO could provide an important link between exercise and its
beneficial effects on diabetes. In this project we examined whether NO plays an important role in the increase
in mitochondrial biogenesis in response to exercise. We provided clear evidence that NO plays an important
role in resting (basal) skeletal muscle mitochondrial biogenesis but not the increase in skeletal muscle
mitochondrial biogenesis in response to acute exercise or exercise training. Based on this we have begun
investigations into other potential regulators of skeletal muscle mitochondrial biogenesis in response to
exercise.
Expected future outcomes:
We have begun investigations into other potential regulators of skeletal muscle mitochondrial biogenesis in
response to exercise, in particular free radicals. We have also obtained NHMRC funding to examine whether
exercise training can correct deficits in skeletal muscle mitochondrial biogenesis in adulthood when one is born
small.
Name of contact:
NHMRC Research Achievements - SUMMARY
Dr Glenn Mcconell
Email/Phone no. of contact:
mcconell@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 350904
CIA Name: A/Pr James Brock
Admin Inst: University of Melbourne
Main RFCD: Autonomic Nervous System
Total funding: $768,560
Start Year: 2005
End Year: 2011
Grant Type: Established Career Fellowships
Title of research award:
Uncoupled Research FellowshipUncoupled Research Fellowship
Lay Description (from application):
Not Available
Research achievements (from final report):
The major focus of this fellowship has been investigation of the effects of nerve injuries on blood vessel
function. In particular, I have provided the first evidence that spinal cord injury (SCI) produces a widespread
increase in the effectiveness of nerves that constrict blood vessels. This change contributes to the development
of dangerous episodes of high blood pressure in SCI patients. These studies also identified potential drug
treatments that reduce the hyper-reactivity of blood vessels following SCI and that may be useful for
preventing these episodes of high blood pressure. We also investigated the use of drug treatments to stimulate
defecation in SCI patients. These studies have provided proof in principal that a chemical which mimics the
actions of the hormone ghrelin stimulates defecation and this is soon to be trialled in SCI patients. In new
studies initiated during the fellowship I investigated the blood pressure lowering effect of ghrelin. This action
has been attributed to ghrelin dilating blood vessels but our studies do not support this action. Instead, our
studies indicate that ghrelin acts somewhere in the brain to decrease the activity of nerves that constrict blood
vessels. This finding is important because low blood levels of ghrelin are associated with elevated blood
pressure. Finally I continued my studies of mechanisms whereby sensory stimuli activate nerves that generate
painful sensations. The highlight of these studies has been the development of a technique that allows the
initiation of action potentials in these nerves to studied for the first time.
Expected future outcomes:
The work on blood vessel function following spinal cord injury is ongoing and is focussing on identifying drug
treatments that prevent the episodes of high blood. I am also investgating whether the changes in blood vessel
function contribute to other complications associated with spinal cord injury such as bladder dysfunction.
Name of contact:
James Brock
Email/Phone no. of contact:
j.brock@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 382903
Start Year: 2006
CIA Name: Prof Stephen Jane
End Year: 2009
Admin Inst: University of Melbourne
Grant Type: NHMRC Project Grants
Main RFCD: Genetic Development (incl. Sex Determination)
Total funding: $623,065
Title of research award:
Defects in epidermal morphogenesis in mammalian Grainyhead-like gene deficient miceDefects in epidermal
morphogenesis in mammalian Grainyhead-like gene deficient mice
Lay Description (from application):
The cells of the skin play an essential role in development of the mammalian embryo. They are critical for
closure of the brain and spinal cord, for forming a protective barrier against infection and noxious stimuli, for
preventing excess fluid loss, for repair of defects and wounds, and for the generation of hair. Our laboratory
has identified a family of genes that are critical for all these processes. Loss of individual members of the
family has different consequences and the aim of this study is to determine the relationship between the genes
to further our understanding of the skin and its functions. These studies have direct and important relevance to
human conditions such as the congenital birth defects spina bifida and anencephaly, and infant prematurity
where the skin is underdeveloped and lacks barrier function. They also have relevance to wound healing and to
conditions in which hair growth is affected, such as alopecia. We believe that therapeutic interventions and
prenatal diagnostic tests could evolve from these studies.
Research achievements (from final report):
This grant identified and characterized a family of genes that are master regulators of the functions of the
human skin. They are essential for wound repair, formation and maintenance of the skin barrier, hair anchorage
and developmental events that require directional migration of the skin. Our findings have potential benefits in
premature infants, where the barrier fails to form, wound repair and a range of other skin defects.
Expected future outcomes:
We anticipate that this grant will form the basis of extensive further work on this gene family that will impact
on our understanding of diseases of the skin.
Name of contact:
Stephen Jane
Email/Phone no. of contact:
Stephen.Jane@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 400089
CIA Name: Prof John Wark
Admin Inst: University of Melbourne
Main RFCD: Endocrinology
Total funding: $469,605
Start Year: 2006
End Year: 2008
Grant Type: NHMRC Project Grants
Title of research award:
The effect of antiepileptic medication on indices of bone health and risk factors for falls and fracturesThe effect
of antiepileptic medication on indices of bone health and risk factors for falls and fractures
Lay Description (from application):
Epilepsy is a common brain disorder and most patients with epilepsy take anti-epileptic drugs (AEDs) for many
years. These patients have high rates of bone fractures, but the reasons are uncertain. Earlier studies identifying
an association between AED use and bone disease were performed on institutionalised patients, and more
recent studies on outpatient populations have been conflicting. A better understanding of this problem is critical
for designing potential preventive measures and treatments. One important additional mechanism by which
AEDs may increase fracture risk is impairment of gait and balance, leading to a high risk of falls. We have
novel data demonstrating the power of a Twin and Matched Sibling approach to study this important problem.
This study showed that chronic AED use was associated with significant deficits in bone mineral density
(BMD), a key predictor of the risk of fractures. The proposed project will ask the following questions: 1. Is
BMD and estimated bone strength lower in the bones most at risk for fracture in women and men chronically
taking AEDs? 2. Is the loss of bone in measurements over time greater in patients continuing to take AEDs? 3.
Is the risk of bone loss greater for certain types of AEDs, and is the risk influenced by length of exposure, age
and menopausal status? 4. How does AED treatment lead to reductions in BMD and bone strength? 5. Are
measures of muscle strength, gait and balance impaired in patients taking AEDs compared with matched
people not taking AEDs? The proposed study will utilise twins and pairs of siblings to investigate the effects of
the long-term use of AEDs for epilepsy on measures of bone mass and strength, indices of bone turnover,
vitamin D status, calcium regulating hormones, mineral levels, sex hormone levels, and measures of muscle
strength, gait and balance function. In addition, a group of patients newly commencing AED treatment for
epilepsy will be studied over 2 years.
Research achievements (from final report):
, Anti-epileptic drugs (AEDs) are required long-term for patients with epilepsy and several other disorders.
Fractures are a major adverse outcome in people taking AEDs. , This project explored the causes of AEDassociated bone fractures using several approaches. One was the powerful exposure-discordant twin/ sibling
pair model, where one member of each pair used AEDs and the other did not. We found significant deficits in
bone mineral density (a key indicator of bone fragility) in people taking AEDs; a person's age and duration of
treatment added to their risk. , The second approach was a cohort study in newly-diagnosed epileptic patients
and non-treated subjects, following indices of bone health for 2 years. This study demonstrated accelerated
bone loss (e.g., at the hip) in newly-treated patients. Further observations may identify specific AEDs that
cause bone loss and fractures. , We also conducted a comprehensive assessment of falls risk in AED-treated
subjects and their non-treated twins and siblings, identifying multiple balance impairments in the AED-treated
subjects. Poor balance and bone fragility are therefore key determinants of the increase in fractures associated
with AED use. A survey of 150 epilepsy patients identified many with high falls risk, confirming the need for
intervention in this population. , This research is unique and important, improving understanding of AEDassociated fracture risk. We are now launching the first specific treatment trial for AED-associated bone loss
and plan a physcial activity intervention trial seeking to reduce AED-associated falls. Our ultimate aim is to
improved bone health in people taking AED therapy.
Expected future outcomes:
Over the next ive years we expect to complete the first RCT of treatment for AED-induced bone loss, to
conduct the first physical activity RCT in prevention of falls during AED therapy and to have translated the
findings into improved clinical care and outcomes for AED-treated patients.
NHMRC Research Achievements - SUMMARY
Name of contact:
Professor John D Wark
Email/Phone no. of contact:
jdwark@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 400139
CIA Name: Prof Ego Seeman
Admin Inst: University of Melbourne
Main RFCD: Endocrinology
Total funding: $751,823
Start Year: 2006
End Year: 2008
Grant Type: NHMRC Project Grants
Title of research award:
Structural Basis of Femoral Neck StrengthStructural Basis of Femoral Neck Strength
Lay Description (from application):
Fractures, in particular femoral neck (FN) fractures, are a huge public health problem resulting in disabilities,
mortality and financial cost to the community. The prevention of these fractures is based on estimation of bone
strength. The decision whether someone needs treatment, or the effectiveness of a treatment can only be judged
by estimating bone strength. The bottom line is that currently we cannot correctly estimate bone strength.
Present methods such as bone mineral density (BMD) perform poorly. Most people who fracture are not
detected by BMD because their BMD is either normal or high, and many people with low BMD never fracture.
The main aim of this grant application is to develop new tools to allow doctors and scientists worldwide to
better estimate FN strength. To develop new methods to replace BMD, scientists need to make use of the 3D
aspects of the bone such as size, shape and internal architecture. Presently, these 3D aspects (structure) have
not been adequately studied and scientists incorrectly approximate them. As a result new methods are not any
better. A good quantification of structure is needed. Another reason for the failure to accurately estimate the
strength of bones is that estimates are based on a single parameter whereas the bone, like any architectural
structure (e.g. building), comprises many components acting together to maintain its strength. To determine the
strength based on density alone is incorrect; the size, the shape and things inside the structure need to be
considered as a whole. After quantifying correctly the structure and components of bone strength, we will
determine how they can be used individually and together to better estimate the strength of the FN in men and
women. Tools generated will be used to better determine people likely to fracture and needing treatment; to
better tailor and monitor treatments. A better understanding of the causes and epidemiology of fractures will
ensue.
Research achievements (from final report):
Research in osteoporosis has focused in the role of trabecular bone (the spongy bone inside the cortical shell)
loss as the cause of osteoporosis because it was commonly believed that bone loss with advancing age is
largely trabecular. In this project we demonstrate that bone loss and fragility in old age originates not from the
trabecular compartment, but from the cortical compartment (outer shell of bone). This work received an award
from the American Society for Bone and Mineral Research., Furthermore, we identified the mechanism
through which the cortical bone becomes fragile - that is, by enlargement and fusions of the holes inside the
cortex, in particularly next to the marrow cavity. The end result of this process is the transformation of a
previously compact cortex in young age into a spongy-like structure in old age leading to fragility., We showed
that this process is poorly detected by bone densitometry ( the currently used diagnosis tool) and this may
explain why most people with fragile bones are missed when the bone density test is used. Understanding of
the process has led us to develop a new diagnostic test. This test is currently subject to a patent application and
its ability to improve fracture prediction will be tested soon., Insights into how bone size, shape and bone
quality interact to make bone strong were have also being studied.
Expected future outcomes:
It is expected that quantification of porosity in clinical settings will allow better identification of individuals at
risk for fracture. Funds have been requested to test this hypothesis.
Name of contact:
Ego Seemna
Email/Phone no. of contact:
egos@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 400341
Start Year: 2006
CIA Name: Dr Simon Murray
End Year: 2008
Admin Inst: University of Melbourne
Grant Type: NHMRC Project Grants
Main RFCD: Neurosciences not elsewhere classified
Total funding: $507,271
Title of research award:
Modulation of Neurotrophin Receptor Signaling: understanding the determinants and phenotypic
consequences.Modulation of Neurotrophin Receptor Signaling: understanding the determinants and phenotypic
consequences.
Lay Description (from application):
Peripheral nerves are complex structures consisting of motor and sensory neurons, their axons, and the cells
that support them, Schwann cells. Peripheral neuropathy is a common neurological problem which covers
many disorders of the peripheral nervous system. There are predominately two types of neuropathies: those
where there is a primary loss or degeneration of neurons and/or their axons; and those where the Schwann cells
are lost. These degenerative pathologies have prompted interest in the potential of growth factors as a general
therapy for peripheral neuropathy. The neurotrophins are a family of neuronal growth factors that influence
many key aspects of neuronal development, as well as the maintenance of the mature peripheral nervous
system. Work in cells in vitro and in animal models provides solid support for the hypothesis that the
neurotrophins prevent neuronal death. However clinical trials testing the neurotrophins has led to variable
results and side effects due to their many effects. To make these therapies useful, it is crucial to expand our
knowledge about how they actually work and which of the many responses they induce actually produces their
beneficial effect. This project aims to achieve this goal. I have identified a mechanism where neurotrophin
signaling is selectively modulated in vitro. The aims of this project are to understand how this modulation of
neurotrophin signaling is mediated, to identify the cellular substrates that are selectively activated and to
determine what the biological consequences of this modulation are. Only through analyses such as these can
we gain new insights into neurotrophin signaling and develop an understanding of how the activities of
neurotrophins can be more precisely harnessed to generate new and more productive therapeutic approaches.
Research achievements (from final report):
The family of growth factors known as the neurotrophins exert profound influences on the devlopment,
survival and maintenace of the mature nervous system, as well as playing critical roles in higher order
functions such as learning and memory. This is achieved through their capacity to signal through an established
cohort of receptors that are primarily expressed on neurons. We have recently identfied a novel co-receptor for
the neurotrophins, called NRH2, and as a direct result of this grant have (i) identified that NRH2 is capable of
forming interactions with other neurotrophin receptors and established the basis of these interactions, (ii) found
that co-expression of NRH2 modifies neurotrophin signaling and identified the molecular basis underpinning
this effect, and (iii) investigated the impact this altered signaling has on neurotrophin signaling and its
biological outcomes. Collectively, these studies represent a substantial advance in our understanding of how
neurotrophin signaling can regulate such a divers array of biological effects, in identifying that through
utilising distinct co-receptors, that the nature and duration of neurotrophin signaling cascade can be
dramatically altered. Taken in context, these findings are significant as they move us closer to understanding
the full complement of factors that regulate neurotrophin signaling, which is important if their beneficial effects
are to be harnessed in the future for therapeutic benefit.
Expected future outcomes:
Now we have established that NRH2 influences neurotrophin signaling and identified the basis of this effect,
our future studies will be directed at investigating how we can utilise this knowledge in specifically regulating
neurotrophin signaling, to manipulate the signals that regulate neuronal survival and differentiation in a
therapeutically beneficial context.
Name of contact:
Simon Murray
NHMRC Research Achievements - SUMMARY
Email/Phone no. of contact:
ssmurray@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 400388
Start Year: 2006
CIA Name: A/Pr Paul McCrory
End Year: 2010
Admin Inst: University of Melbourne
Grant Type: Career Development Fellowships
Main RFCD: Neurology and Neuromuscular Diseases
Total funding: $370,603
Title of research award:
Concussive injury in children and adolescents.Novel imaging modalities in adult concussive brain
injuryConcussive injury in children and adolescents.Novel imaging modalities in adult concussive brain injury
Lay Description (from application):
Not Available
Research achievements (from final report):
, My clinical research work has studied the clinical aspects of traumatic brain injury (TBI). This has been
especially important in the understanding of the effects of mild TBI in paediatric age groups where little is
known about the appropriate management of such injuries. In additon, the research has provided the basis of
utilising novel radiological techniques in adult TBI particularly in the setting of sports related TBI.
Expected future outcomes:
, This research is critical in the development of clinical pathways for mild TBI management. The guidelines
developed for the management of sports concussion have already been utilised worldwide in all profession
team sports
Name of contact:
N/A
Email/Phone no. of contact:
N/A
NHMRC Research Achievements - SUMMARY
Grant ID: 409966
CIA Name: A/Pr Stuart Kinner
Admin Inst: University of Melbourne
Main RFCD: Health and Community Services
Total funding: $1,894,013
Start Year: 2007
End Year: 2013
Grant Type: NHMRC Strategic Awards
Title of research award:
PASSPORTS TO ADVANTAGE: Health and capacity building as a basis for social integrationPASSPORTS
TO ADVANTAGE: Health and capacity building as a basis for social integration
Lay Description (from application):
This project will conduct a randomised controlled trial of a post-release intervention for adult prisoners in
Queensland. The findings of the study will inform the development of an evidence-based post-release
intervention for prisoners in Australia and elsewhere, as well as providing an unprecedented insight into the
post-release experiences of prisoners in Queensland.
Research achievements (from final report):
The Passports study evaluated an intervention to increase access to health and social services for recently
released prisoners in Queensland, using a gold-standard 'randomised controlled trial' design. It is the first such
RCT ever undertaken in Australia and one of only a handful internationally. Using a low-cost intervention
developed for the study, we significantly increased access to primary care and mental health services for at
least six months after release from prison.
Expected future outcomes:
We have recently been awarded funding to (a) examine the cost-effectiveness of the intervention, and (b)
examine the links between health outcomes and subsequent offending. A more focussed RCT for prisoners
with serious mental illness is planned.
Name of contact:
A/Prof Stuart Kinner
Email/Phone no. of contact:
s.kinner@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 435112
Start Year: 2007
CIA Name: Prof Stephen Jane
End Year: 2009
Admin Inst: University of Melbourne
Grant Type: NHMRC Project Grants
Main RFCD: Foetal Development and Medicine
Total funding: $569,542
Title of research award:
The role of the mammalian Grainyhead-like gene family in neural tube closureThe role of the mammalian
Grainyhead-like gene family in neural tube closure
Lay Description (from application):
Failure of the skin to close over the brain and spinal cord during human development results in the devastating
congenital birth defects anencephaly and spina bifida, known collectively as the neural tube defects. These are
the second most common congenital birth defects affecting 1:1000 pregnancies. Anencephaly is not compatible
with life and affected babies die at birth. In contrast children with spina bifida survive, but suffer from limb
paralysis, bowel and bladder dysfunction, learning difficulties and psycho-social disturbances. Our laboratories
have identified a family of genes essential for the colsure of the neural tube in mammals. The aim of this
proposal is to understand the mechanisms of action with a view to developing new therapeutics that mey be
used preventatively in these conditions. We also hope that these studies may facilitate the development of a
genetic test to screen couples at risk.
Research achievements (from final report):
Defects in closure of the brain and spinal cord (neural tube defects) are the second commonest of all the
congenital birth defects. Our laboratory has made a substantial contribution in this area with the identification
of the Grainyhead-like gene family which plays critical roles in closure of the neural tube. By studying the
mechanism by which these genes work, we gain insights into potential screening and preventative measures
that could be developed for these devastating defects into the future.
Expected future outcomes:
We anticipate that our studies will lead to new preventative strategies for neural tube defects.
Name of contact:
Professor Stephen Jane
Email/Phone no. of contact:
Stephen.Jane@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 454536
CIA Name: Dr Mary Tolcos
Admin Inst: University of Melbourne
Main RFCD: Central Nervous System
Total funding: $497,280
Start Year: 2007
End Year: 2009
Grant Type: NHMRC Project Grants
Title of research award:
Compromised fetal brain development: neurogenesis and the potential for therapeutic
intervention.Compromised fetal brain development: neurogenesis and the potential for therapeutic intervention.
Lay Description (from application):
Lack of oxygen to the fetal brain during pregnancy is thought to be the main causes of brain injury in
newborns. Some of these infants will suffer developmental and behavioural problems including cerebral palsy,
schizophrenia and epilepsy. Currently, there is no effective treatment to redress these changes in brain
development and this is one of the major challenges in perinatal medicine today. We have previously shown in
a guinea pig model of chronic placental insufficiency (reduced oxygen and nutrient levels during pregnancy)
that there is a reduction in neurons and in the connections between them. This may result from a reduction in
number of newly generated neurons (neurogenesis), or an increase in neuronal death (apoptosis), or both. To
develop therapeutic strategies to improve brain growth and ultimately functional recovery, we must understand
the mechanisms which lead to these brain changes. In this project, we will use our guinea pig model to: 1)
determine whether a suboptimal fetal environment decreases neuronal numbers by influencing neurogenesis,
apoptosis or both, 2) study changes in the compromised brain environment which are likely to influence
apoptosis and neurogenesis, 3) determine whether a suboptimal fetal environment has long-term effects on
adult neurogenesis and 4) determine whether treatment with erythropoietin (Epo), a naturally occurring
hormone, can resolve deficits in brain development and function. Epo is an exciting candidate as it is, or is in
the process of being used to treat stroke and newborn asphyxiation. Epo has also been shown to prevent
neuronal death and promote neurogenesis following brain injury. Understanding the mechanisms and finding
effective treatments for brain damage is a vital area of endeavour if we are to help infants develop their
maximum potential and reduce the enormous social, economic and educational burden which must be borne by
the individual and society in general when things go wrong during pregnancy.
Research achievements (from final report):
Adverse prenatal development contributes to many neurological disorders which manifest postnatally including
cerebral palsy, cognitive and behavioural deficits and possibly schizophrenia. One factor thought to contribute
to these disorders is fetal hypoxia/ischemia (a reduction or loss of oxygen delivery to the fetus). A number of
brain alterations are associated with these disorders including a reduction in the volume of specific brain
regions and neuronal loss. It is likely that prenatal insults such as hypoxia/ischemia will occur during a time
when neurons are being developed therefore this important developmental process may be disrupted. Indeed,
using a model of prenatal compromise (placental insufficiency and fetal hypoxia) in the guinea pig, our group
has previously demonstrated a reduction in the number of neurons, inappropriate wiring of the brain and
abnormal brain function. The aim of this project was to understand the mechanisms underlying these brain
alterations in order to develop a novel approach to the effective treatment of such injury. Using our model of
prenatal compromise we found that there is an increase in neuronal proliferation in the brains of compromised
fetuses and that this increase is correlated with the severity of the insult. Although we know that ultimately
there are fewer neurons, it appears that the compromised brains may contain an intrinsic mechanism that
regulates the production of neurons in an attempt to "catch-up". It is unlikely that this increased production of
neurons is sustained long-term, but understanding this mechanism may be the key to developing novel
therapies.
Expected future outcomes:
We hope to further investigate the mechanisms underlying the increase in neuronal proliferation in the
prenatally compromised brain. In addition, understanding the composition of the cerebral microenvironment,
and which of its components are altered by prenatal insults, may provide further insight into the development
of appropriate and more targeted therapies.
NHMRC Research Achievements - SUMMARY
Name of contact:
Dr Mary Tolcos
Email/Phone no. of contact:
m.tolcos@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 454561
CIA Name: Prof Gordon Lynch
Admin Inst: University of Melbourne
Main RFCD: Sports Medicine
Total funding: $288,210
Start Year: 2007
End Year: 2009
Grant Type: NHMRC Project Grants
Title of research award:
Improving muscle function after injury: Novel tissue engineering strategies for exercise, surgery and sports
medicineImproving muscle function after injury: Novel tissue engineering strategies for exercise, surgery and
sports medicine
Lay Description (from application):
Muscles can be injured by excessive strains when playing sports, in road and workplace accidents, and during
plastic and reconstructive surgery. Some surgeries require an unavoidable interruption to the muscle's normal
blood supply (called 'ischaemia'). Subsequent return of the muscle's blood supply (reperfusion) is problematic
in that a severe secondary muscle injury can ensue mediated by the influx of damaging free radicals when
blood flow is restored. Tissue-engineering provides a novel therapeutic approach to restore muscle structure
and function to damaged muscles after injury or disease. Our recent research using controlled release of
growth factors from biodegradable hydrogels has exciting application for muscle repairafter injury. We will
utilize these cutting edge tissue engineering strategies to deliver to damaged muscles a hydrogel containing
controlled delivery (slow release) microcapsules loaded with an anabolic agent (the beta-agonist, formoterol)
and/or a growth factor (IL-15) designed to enhance functional muscle repair after three distinct but clinically
relevant models of muscle injury: a) crush injury: A model for muscle injuries on the sports field, in the
workplace, and those associated with road trauma; b) ischaemia-reperfusion injury: a model for muscle damage
associated with surgical interventions, muscle transfers for functional restoration, and other injuries associated
with plastic and reconstructive surgery; and c) contraction-induced injury: a model for strain injuries such as
hamstring muscle tears that can occur on the sports field. After injury we will assess functional muscle repair
using a comprehensive series of histological, biochemical, molecular, immunochistochemical, and
physiological techniques. The research has broad application to exercise and clinical medicine; including
sports, emergency and rehabilitation medicine, and plastic, reconstructive, and orthopaedic surgery.
Research achievements (from final report):
Musculoskeletal injuries represent a major global public health problem and skeletal muscle damage and loss
of muscle function contributes significantly to the large burden of disability and suffering. Novel approaches
that can attenuate the severity of muscle trauma and/or hasten muscle repair to restore function would help to
reduce the economic burden of musculoskeletal injury and alleviate the personal suffering and financial
hardship of affected patients. Using novel tissue engineering approaches, we developed small spheres capable
of being loaded with the muscle growth promoting agent, formoterol. When injected into damaged muscles, the
goal was that the spheres slowly released the formoterol such that it prolonged the growth promoting effect
beyond that achieved normally from simply injecting muscle growth promoting agents directly into muscles.
The work represent a significant advance for the development of new therapeutics for muscle repair following
injury.
Expected future outcomes:
The research will identify new ways of utilising tissue engineering to enhance the repair of skeletal muscle
after injury, with relevance to advancements in plastic and reconstructive surgery, sports medicine and
rehabilitation.
Name of contact:
Prof. Gordon S. Lynch
Email/Phone no. of contact:
gsl@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 454686
Start Year: 2007
CIA Name: Prof Kim Bennell
End Year: 2008
Admin Inst: University of Melbourne
Grant Type: NHMRC Project Grants
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $271,503
Title of research award:
Reducing knee load and slowing disease progression with conservative interventions in knee
osteoarthritisReducing knee load and slowing disease progression with conservative interventions in knee
osteoarthritis
Lay Description (from application):
Knee arthritis is a painful, disabling, costly condition particularly affecting the elderly. As there is presently no
cure for arthritis, interventions that slow progression of the disease will reduce the personal and societal burden
of arthritis. Recently it has been postulated that specific exercise that targets how the muscles are controlled by
the nervous system may have greater disease-modifying effects than exercise aimed at strengthening the
muscles. Data are beginning to highlight the complexity of muscle strategies adopted by the nervous system to
compensate for joint derangement in knee arthritis. It is our contention that there may be specific strategies that
provide more optimal knee joint loading in relation to slowing disease progression. The first part of this project
is to investigate knee control in people with knee arthritis and to evaluate whether this influences disease
progression. This will provide the basis for refinement and optimisation of rehabilitation interventions for this
patient group. The second part of this project will investigate whether strengthening the hip muscles in patients
with knee arthritis influences knee load and hence disease progression. Hip muscle strengthening is currently
not routinely included as part of the management of knee arthritis. If the results of this project find it to be
effective, then hip muscle strengthening can be recommended for treating knee arthritis.
Research achievements (from final report):
This research investigated factors influencing knee load during walking and ways to reduce knee load in people
with knee osteoarthritis. This is important as knee load is a predictor of the risk of structural disease
progression - those who walk with higher knee load are more likely to progress to more serious disease. The
research showed that muscles around the hip are weaker in people with knee osteoathritis but that strengthening
the hip muscles does not change knee load although it leads to a significant reduction in knee pain and
improvement in knee function. This suggests that hip muscle strengthening is not a disease-modifying
treatment as has been postulated in the literature. The research also showed that neuroumuscular and
biomechanical factors can influence knee load and hence disease progression. This will impact upon the design
of more effective rehabilitation programs for knee osteoarthritis.
Expected future outcomes:
The research provides information that will influence rehabilitation programs for people with knee
osteoarthritis that will be of use to clinicians
Name of contact:
Kim Bennell
Email/Phone no. of contact:
k.bennell@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 454693
Start Year: 2007
CIA Name: Dr Patrick Humbert
End Year: 2009
Admin Inst: University of Melbourne
Grant Type: NHMRC Project Grants
Main RFCD: Cellular Interactions (incl. Adhesion, Matrix, Cell Wall)
Total funding: $516,078
Title of research award:
Regulation of epithelial migration by Scribble in development and wound repairRegulation of epithelial
migration by Scribble in development and wound repair
Lay Description (from application):
The movement of epithelial cells within our body (the cells that form the thin protective layer on exposed
bodily surfaces such as skin and the lining of internal cavities, ducts, and organs) is essential for our normal
embryonic development as well as for healing of wounds following injury. Understanding how this movement
is regulated is therefore a fundamental area of medical biology. Although much is known about the mechanics
of how a cell moves, the signals used to coordinate this movement so as to ensure that each cell migrates to the
right place during embryonic development or in response to a wound is not well understood. A number of lines
of evidence suggest that proteins required for the correct orientation of cells within our body (a property of
cells known as polarity) may be essential for this process. Mutation of the polarity protein Scribble in the fly,
zebrafish and mouse causes a disorganization of epithelial tissues during embryonic development. We have
now shown that Scribble is required for cells to orientate correctly so as to be able to move in response to a
wound in tissue culture and also during embryonic development and wound healing in the mouse. It is
currently unknown how Scribble regulates migration. Here we propose to identify the molecules that Scribble
regulates to coordinate cell movement during development and tissue repair. These studies will provide new
insights into the fundamental process of how cell movement is coordinated and could lead to novel strategies
for improved treatment of tissue injuries.
Research achievements (from final report):
Control of cell migration is essential for normal development and in situations requiring tissue homeostasis
such as wound healing. Understanding the regulation of migration is therefore a fundamental area of medical
biology. Although much is known about the mechanics of migration itself, the signals used to coordinate
migration during development or in response to tissue injury are poorly understood. A number of lines of
evidence suggest that proteins required for the orientation ("polarization") of cells as they migrate may be
essential for this process. We have now shown that human Scribble is required for the polarity associated with
directed migration in response to a wound or chemokine gradient in vitro. Furthermore, this function appears
relevant in vivo as mice mutant for Scribble and other members of the Planar Cell Polarity pathway show
defective wound healing of the epidermis. Scribble is therefore a highly conserved positive regulator of
migration in multiple cell types and organisms. We have used a combination of cellular and in vivo studies to
identify and characterize Scribble-dependent pathways involved in migration.
Expected future outcomes:
Migration is a key process during embryonic development and tissue repair. We have identified Scribble and
associated proteins as a protein that is necessary for directed migration in vitro and in vivo. Our studies provide
new insights into these processes that could lead to novel strategies for improved treatment of tissue injuries.
Name of contact:
Dr Patrick Humbert
Email/Phone no. of contact:
patrick.humbert@petermac.org
NHMRC Research Achievements - SUMMARY
Grant ID: 454717
Start Year: 2007
CIA Name: Dr Linda Denehy
End Year: 2009
Admin Inst: University of Melbourne
Grant Type: NHMRC Project Grants
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $359,283
Title of research award:
Evaluation of exercise rehabilitation for survivors of intensive careEvaluation of exercise rehabilitation for
survivors of intensive care
Lay Description (from application):
Intensive care medicine has improved survival in critically ill patients. However, international literature
reports poor quality of life and physical outcomes in ICU survivors compared to people of the same age. In
addition, patients who require a prolonged ICU stay consume a large amount of resources. This project is
testing whether an early ICU physiotherapist-directed exercise rehabilitation program continuing until after
hospital discharge will improve patient's quality of life, physical function and decrease the use of health
resources compared with patients' receiving standard care. Patients in the rehabilitation group will take part in a
physiotherapy exercise rehabilitation program including returning to out patient classes after discharge. The
physiotherapist will treat patients daily during hospital stay then twice weekly for 8 weeks after discharge. All
patients will complete 2 quality of life questionnaires and physical function will be assessed using a new test
developed for the acute ICU stay the 6 minute walk test, which measures how far patients can walk quickly in
6 minutes. The timed up and go test will also be used and it measures how quickly patients can get up from a
chair and walk. An activity monitor, worn on the wrist, for some of the time after discharge will measure how
much exercise and moving about patients are doing at home. Measurements will performed by a
physiotherapist, blinded to the group to which patients were randomly allocated, on admission to the ICU
(quality of life only by proxy), on discharge from the ICU, discharge from hospital and at 3, 6, 12 months after
discharge. Economic evaluation will be performed to examine overall use of resources using information from
the questionnaires.
Research achievements (from final report):
Physical rehabilitation has been advocated for survivors of a critical illness to improve physical function and
health related quality of life. This is the first study to assess the impact of an intensive physical rehabilitation
program commenced in the intensive care unit and continued on the ward and as an outpatient program with
follow up for a 12 month period. It is also the first study to assess the economic impact of such a rehabilitation
program. The results of this trial have been submitted for publication and are currently under review by a
highly ranked international peer reviewed journal. In addition to this several publications have arisen from this
study regarding further development of a tool to measure physical function in the intensive care unit (ICU) and
measurement of physical activity levels in survivors of ICU. Preliminary trial results have been presented at a
number of national and international conferences and forums. International collaborations have been developed
in the USA and UKwith the view to developing future trials in the area. Measurement tools which were further
developed during the trial are now being used in international studies of ICU survivors.
Expected future outcomes:
Development of Australian guidelines for standard rehabilitation programs will lead to improved outcomes for
surviors of critical illness. Rehabilitation programs need to target specific groups within this population who
will benefit most from these services. In addition, factors which may affect participation along with the timing
and delivery mode of these services need to be assessed.
Name of contact:
Associate Professor Linda Denehy
Email/Phone no. of contact:
l.denehy@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 508925
Start Year: 2008
CIA Name: Prof Mary Galea
End Year: 2012
Admin Inst: University of Melbourne
Grant Type: NHMRC Project Grants
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $382,320
Title of research award:
Pelvic Organ Prolapse Physiotherapy (POPPY)Pelvic Organ Prolapse Physiotherapy (POPPY)
Lay Description (from application):
Pelvic organ prolapse in women is associated with poor quality of life. The standard treatment currently
available for prolapse is surgery. The evidence for conservative management with physiotherapy is not clear.
This randomised controlled trial will examine the effect of physiotherapy treatment, including pelvic floor
muscle training, on prolapse symptoms and severity, compared with lifestyle advice only. Appropriate
conservative management may reduce the need for surgery and associated costs.
Research achievements (from final report):
Pelvic organ prolapse (POP) is highly prevalent in women over 40 years (40-50%) and is considered a major
epidemic. Symptoms of POP impact substantially on quality of life for women, affecting physical health and
well-being, ability to exercise and personal relationships. Typical management involves surgery, which has a
high failure rate. This project has contributed to two independent but complementary randomised controlled
trials, one conducted in the UK and the other in Australia, investigating the effectiveness of conservative
management of POP using pelvic floor muscle training. Both studies showed that pelvic floor muscle training
was effective and cost-effective (UK) in minimizing the severity and bother of prolapse symptoms compared
with lifestyle advice about weight loss, constipation, and avoidance of heavy lifting, coughing and high impact
exercise. This evidence is sufficient for pelvic floor muscle training to be recommended as first-line
management for prolapse.
Expected future outcomes:
The implementation of pelvic floor muscle training for women with prolapse may prevent the need for surgery,
prolong the time before a surgical procedure is required, and may improve the durability of the first surgical
procedure being undertaken, possibly avoiding the need for repeat surgery.
Name of contact:
Helena Frawley
Email/Phone no. of contact:
h.frawley@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 508947
CIA Name: Prof John Furness
Admin Inst: University of Melbourne
Main RFCD: Autonomic Nervous System
Total funding: $414,327
Start Year: 2008
End Year: 2010
Grant Type: NHMRC Project Grants
Title of research award:
Roles of the peptide hormone, ghrelin, in the spinal cordRoles of the peptide hormone, ghrelin, in the spinal
cord
Lay Description (from application):
This study investigates the control of internal organs of the body, the heart, blood vessels, intestine and
bladder. We have made the new and surprising discovery that ghrelin, previously known to be a hormone, is
probably also a neurotransmitter in the spinal cord. This raises the possibility that drugs that act on ghrelin
receptors in the spinal cord could be used to treat high blood pressure or other problems of internal organs.
Research achievements (from final report):
We have found that artificial compounds that mimic the action sof the naturally occurring hormone, ghrelin,
have actions in the spinal cord that influence bowel and bladder emptying and blood pressure. These are novel
discoveries. The stimulant effects on bowel emptying can be elicited in conscious animals which show no
adverse effects of the drug application. Thus the mechanism that we have discovered can be potentially used to
treat constipation, such as the constipation that occurs after spinal cord injury or in old age. In addition, the
observations imply that the ghrelin receptor is somehow involved in the maintenance of blood pressure. It is
possible that this sytem could be manipulated to reduce high blood pressure.
Expected future outcomes:
Suitable compounds to treat constipation have been developed and we anticipate that these will be used in
human trials.
Name of contact:
Professor John Furness
Email/Phone no. of contact:
j.furness@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 508966
Start Year: 2008
CIA Name: A/Pr Kay Crossley
End Year: 2011
Admin Inst: University of Melbourne
Grant Type: NHMRC Project Grants
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $616,431
Title of research award:
Patellofemoral arthritis: Efficacy of physiotherapy and understanding the role of joint stressPatellofemoral
arthritis: Efficacy of physiotherapy and understanding the role of joint stress
Lay Description (from application):
Arthritis of the kneecap leads to considerable pain and difficulty with daily activities. This project is testing
whether a physiotherapy treatment (8 sessions over 12 weeks) designed specifically for people with kneecap
arthritis is effective. In order to understand more about kneecap arthritis, this project will calculate the force on
the kneecap and its relationship to pain and other factors, including thigh and hip muscle strength, knee
alignments and knee movements.
Research achievements (from final report):
, The patellofemoral joint (PFJ), or kneecap, is one compartment of the knee that is frequently affected by
osteoarthritis (OA) and is a potent source of symptoms. However, there are few treatments for PFJOA.
Therefore, this project aimed to evaluate whether a physiotherapy treatment, targeted to the PFJ, resulted in
greater improvements in pain and physical function than a physiotherapy education treatment., We conducted a
clinical trial in 92 people with PFJ OA. We observed that the targeted physiotherapy resulted in greater
improvements than the education group for perceived pain and function at 3 months. , We also determined the
force in the PFJ, on a patient-specific basis using computer modelling. We observed that people with PFJ walk
up and down stairs with lower PFJ forces, muscle size and forces than people with no OA., Significance:, Our
physiotherapy treatment, targeted to the PFJ, resulted in superior outcomes than a physiotherapy-led education
treatment for PFJOA. Therefore, treatments for knee OA may be enhanced by targeting treatments to the
compartment most affected by the disease. The project's outcome will influence knee OA rehabilitation, thus
reducing the personal and societal burden of this increasing public health problem. Our findings also have the
potential to foster development of interventions that may prevent PFJ OA, .
Expected future outcomes:
The results of these studies should increase the awareness of the importance of PFJ OA. The results may lead
to improved treatment options for people with PFJ OA. We will also use the results of these studies to evaluate
treatments with potential to reduce development, or progression of PFJ OA.
Name of contact:
Associate Professor Kay Crossley
Email/Phone no. of contact:
k.crossley@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 509015
Start Year: 2008
CIA Name: A/Pr Pritinder Kaur
End Year: 2013
Admin Inst: University of Melbourne
Grant Type: NHMRC Research Fellowships
Main RFCD: Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology)
Total funding: $690,502
Title of research award:
Uncoupled Research FellowshipUncoupled Research Fellowship
Lay Description (from application):
I am a stem cell biologist investigating the cellular and molecular mechanisms of tissue renewal and
carcinogenesis in epithelial tissues.
Research achievements (from final report):
Our research has provided a greater understanding of the skin regenerating properties of stem cells compared to
their more mature progeny and the types of factors that may control stem cell behaviour. We have also
advanced current knowledge of the cells that make up the immediate environment of the skin regenerating stem
cells and the molecules/factors they produce that could be harnessed for cell transplantation. Our research also
advances current understanding of cells found in the microenvironment of epithelial tumours such as nonmelanoma skin cancers and ovarian cancer that can be diverted to accelerate the rapid growth of primary
tumours and assist in their malignant dissemination throughout the body in the form of metastases.
Expected future outcomes:
We expect that the knowledge gained from our studies will i assist in developing means to improve the
expansion of skin cells in the laboratory prior to transplantation onto patients with large skin deficiencies such
as burns; and ii assist in devising a simple test for predicting ovarian cancer patients at greater risk of relapse
and death.
Name of contact:
Pritinder Kaur
Email/Phone no. of contact:
pritinder.kaur@petermac.org
NHMRC Research Achievements - SUMMARY
Grant ID: 509146
CIA Name: A/Pr Heung-Chin Cheng
Admin Inst: University of Melbourne
Main RFCD: Cellular Nervous System
Total funding: $519,715
Start Year: 2008
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
Deciphering how PTEN phosphatase mediates excitotoxic neuronal deathDeciphering how PTEN phosphatase
mediates excitotoxic neuronal death
Lay Description (from application):
In stroke patients, oxygen deprivation indirectly induces massive nerve cell death by activating a cell deathpromoting enzyme called PTEN. We aim at unravelling (i) how PTEN is activated by oxygen deprivation, (ii)
where the activated PTEN is localised in cells, and (iii) how the activated and optimally localised PTEN
induces nerve cell death. The study will benefit development of therapeutic strategies to protect against brain
damage in stroke.
Research achievements (from final report):
We found that upon overstimulation of the cultured neurons by glutamate, PTEN and its down-stream substrate
c-Src kinase, undergoes calpain-mediated limited proteolysis to generate a 50-kDa truncated PTEN and an 55kDa truncated c-Src. Further investigation reveals that the truncated c-Src is the key enzyme directing neuronal
cell death. Our finidngs indicate that inhibitors suppressing c-Src kinase activity and/or calpain-mediated
truncation of c-Src are potential neuroprotectants for prevention of neuronal death in patients suffering from
ischaemic stroke.
Expected future outcomes:
development of c-Src kinase inhibitors as neurprotectants for treatment of stroke patients. As PTEN is an
endogenous inhibitor of c-Src kinase, studying how truncation of c-Src kinase allows it to escape regulation by
PTEN will shed light on the mechanism of neuronal death in stroke patients.
Name of contact:
Heung-Chin Cheng
Email/Phone no. of contact:
heung@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 509215
CIA Name: Prof Stephen O'Leary
Admin Inst: University of Melbourne
Main RFCD: Otorhinolaryngology
Total funding: $544,890
Start Year: 2008
End Year: 2010
Grant Type: NHMRC Project Grants
Title of research award:
Auditory nervous system function after treatment with trophic agentsAuditory nervous system function after
treatment with trophic agents
Lay Description (from application):
Partial or complete deafness affects 11% of Australians and has great personal, social and economic cost .
Worldwide, over 60,000 deaf people can now understand spoken language because of the Bionic Ear.
However, after prolonged deafness, the nerves in the ear that the BIonic Ear stimulates die, reducing hearing
quality. Our research tests whether biological interventions with nerve growth factors and nerve stimulation
can preserve nerve function and improve hearing with the Bionic Ear.
Research achievements (from final report):
Neurotrophins are potent drugs that can protect against damage to the nerves of the inner ear in deafened
aniamals. However until now, we did not know what effect neurotrophins may have on hearing. We established
a model where we can deliver neurotrophins to the inner ear of guinea pig, through the round window
membrane of the cochlea, without perturbing the hearing. We found that after four weeks, BDNF resulted in
improved hearing so that guinea pigs could detect sounds at lower intesities than they could before
neurotrophin treatment. We have also found that neurotrophins applied to the inner ear after deafness can
prevent degeneration that occurs in parts of the brain involved in hearing. Neurotrophins prevented the
shrinkage and damage to brain cells in the cochlear nucleus of the brain, normally seen after deafness and also
prevented the loss ions channels that are involved in activating these brain cells. We aim now to further
explorer these interesting findings to detemine if neurotrophins may help prevent or restore gradual hearing
loss, such as that which occurs with ageing.
Expected future outcomes:
Future planned studies in guinea pigs will determine the mechanism for the effect of neurotrophins on hearing,
the therapeutic dose and optimal duration of treatment. From here we hope to determine if promising effect of
neurotrophins at improving hearing will translate to patients who have progressive hearing loss.
Name of contact:
Professor Stephen O'leary
Email/Phone no. of contact:
sjoleary@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 509217
CIA Name: Prof Philip Beart
Admin Inst: University of Melbourne
Main RFCD: Cell Neurochemistry
Total funding: $747,928
Start Year: 2008
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
Mitochondria: molecular and cellular insights into their diverse contributions to neuronal injuryMitochondria:
molecular and cellular insights into their diverse contributions to neuronal injury
Lay Description (from application):
Mitochondria are components of cells normally providing energy for essential functions and in the energy
demanding brain, under stress conditions, mitochondria acts as controllers of cellular decision-making
processes leading to neuronal death. Our goal is to understand mitochondrial mechanisms determining how
neurones die after various stresses and injury. Using pathological insults relevant to neurological conditions,
we shall analyse "death" molecules and how neurones adapt when threatened.
Research achievements (from final report):
, Neurones die by various mechanisms in neurodegenerative conditions and understanding "death" is essential
in rescuing injured neurones. Our work was aimed at dissecting neuronal death mechanisms and studies were
undertaken in neurones isolated from animals and then maintained under physiological conditions. Herein it is
possible to "model" the cellular stresses to which brain cells are exposed in human neuropathologies. By
challenging cultured neurones with toxic stimuli (oxidative stress, excitotoxicity, growth factor deprivation)
known to operative in human neurodegeneration, we described for the first time the full cascade of death
signalling, including the mobilization of proteins from mitochondria (organelles for energy generation) that
initiate injurious events. Recruitment of four types of neuronal death identified (apoptosis, necrosis,
programmed necrosis & autophagy) was dependent on the type and effective magnitude of the toxic stimulus.
Little is known about one form of neuronal death, gene-programmed necrosis, and we identified endonucleaseG as contributing intimately to the death signalling. This finding is totally novel, especially since blockade of
its involvement was neuroprotective, and suggested endonuclease-G is intimately linked to oxidative injury
which is strongly implicated as contributing to brain cell death in stroke. In some cases multiple death
mechanisms were recruited - interestingly autophagy (a cellular debris removal system) was found to
contribute to neuronal death in concert with oxidative stress-induced programmed necrosis. Since autophagy
has protective ("good") and destructive ("bad") components, selective activation of the good component to
remove damaged cellular components represents a novel way to minimize the debilitating effects of
neurodegenerative conditions.
Expected future outcomes:
Our findings need to be extended in vivo to determine if programmed necrosis and autophagy represent
genuine "targets" for rescuing injured brain. We need to delineate the interface between autophagy and the
second debris removal system, the ubiquitin-proteasome. These goals are being pursued in a mouse model of
human stroke.
Name of contact:
Professor Philip Beart
Email/Phone no. of contact:
philip.beart@florey.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 509310
Start Year: 2008
CIA Name: Dr Kerrie Sanders
End Year: 2008
Admin Inst: University of Melbourne
Grant Type: NHMRC Project Grants
Main RFCD: Medical and Health Sciences not elsewhere classified
Total funding: $104,995
Title of research award:
Does An Annual High Dose Vitamin D Supplement Decrease Healthcare Utilisation in Older Women?Does An
Annual High Dose Vitamin D Supplement Decrease Healthcare Utilisation in Older Women?
Lay Description (from application):
The shorter bleaker days of winter can cause a vitamin D deficiency in Australian women, increasing their risk
of osteoporosis and broken bones including hip fracture. New research suggests that the low winter levels of
the vitamin may not be good for us in many ways and the NHMRC is funding a Geelong-based study to
determine if Austrlia's elderly can improve their overall health by taking a once-a-year dose of vitamin D
tablets.
Research achievements (from final report):
Recent research suggests that higher levels of vitamin D in your blood may provide protection from many
disorders such as diabetes, osteoporosis, depression and certain types of cancer. This project represents the first
international study to investigate this hypothesis using a randomised, placebo-controlled clinical trial. The
hypothesis was that older women supplemented annually for 3 to 5 years with a high oral dose of vitamin D3
(500,000 IU) would use fewer healthcare services than those given placebo (dummy) tablets. The preliminary
analysis using data from Medicare Australia suggests there is no difference between the groups and that the
women randomised to vitamin D used the same number of Medicare services as women receiving placebo
(vitamin D group: 28.5 and placebo group: 28.0 Medicare services per person per year). The age of participants
did not differ between the groups (vitamin D: 76.8 years and placebo: 76.7 years). In the year prior to
commencing the study medication the women used an average of 18.5 services per person (vitamin D group:
18.6 and placebo group: 18.5). These results also suggest that women aged 70+ years had a 1.5 fold increase in
the average number of healthcare service/visits they used each year over a 2 to 3 year period and that this
increase did not differ between those given vitamin D and placebo.
Expected future outcomes:
Further analysis of the data will determine the cost of healthcare services between the vitamin D and placebo
groups to determine if there is a significant difference in the type of health services used and the total cost of
health service utilisation between the two groups. The data will be analysed by age group using 70-74; 75-79;
and 80+ years and stratified by fracture (yes/no).
Name of contact:
A/Prof Kerrie Sanders
Email/Phone no. of contact:
kerrie@barwonhealth.org.au
NHMRC Research Achievements - SUMMARY
Grant ID: 509317
CIA Name: A/Pr Paul Whitington
Admin Inst: University of Melbourne
Main RFCD: Neurogenetics
Total funding: $426,006
Start Year: 2008
End Year: 2010
Grant Type: NHMRC Project Grants
Title of research award:
The role of cell adhesion molecules in regulation of axon advanceThe role of cell adhesion molecules in
regulation of axon advance
Lay Description (from application):
All cells contain on their surface a class of molecules, cell adhesion molecules, that enable them to adhere to
other cells in tissues. Cell adhesion molecules have long been known to be involved in the guidance of axons to
their targets during development. However the molecular mechanisms by which these molecules act are largely
unknown. We propose to use the powerful genetic tools available in the fruitfly to dissect the mechanisms by
which two cell adhesion molecules promote axon growth.
Research achievements (from final report):
As the embryo grows, nerve cells send out long extensions called axons, which make connections with specific
target cells, thereby wiring up the nervous system. The aim of this project was to enhance our understanding of
how axon growth is regulated at a molecular level. We have focussed on two proteins belonging to a class of
molecules called cell adhesion molecules (CAMs), which bind cells together in tissues. CAMs have long been
known to be important players in axon growth regulation, but how they act is poorly understood. Our research
has shed new light on this problem, information that may assist the development of therapies for repairing
damaged spinal cord axons following injury or disease. Our findings suggest that one of the CAM proteins
under study promotes the growth of axons by physically linking them to other axons within the nerve. The
other CAM protein acts in a different way. While, like the first protein, it promotes axon advance, it does so,
not by linking the axon to its neighbours, but by acting as a receptor on the surface of the axon for growth
promoting signals. We have identified at least one of the proteins inside the axon that cause it to grow forwards
when this receptor protein binds signalling molecules. While it has been previously suggested that this
particular signalling pathway might be involved in axon growth, our research has provided the first definitive
evidence for this idea.
Expected future outcomes:
Our research has put us in a position to dissect in detail the molecular pathways involved in the function of
these two axon growth-promoting proteins. This knowledge will present us with possible molecular targets for
triggering the regrowth of axons in the damaged human spinal cord.
Name of contact:
Assoc. Prof. Paul Whitington
Email/Phone no. of contact:
p.whitington@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 509328
CIA Name: Dr Helen MacLean
Admin Inst: University of Melbourne
Main RFCD: Cell Physiology
Total funding: $703,665
Start Year: 2008
End Year: 2010
Grant Type: NHMRC Project Grants
Title of research award:
Role of non-classical actions of androgens in musculoskeletal physiologyRole of non-classical actions of
androgens in musculoskeletal physiology
Lay Description (from application):
Androgens (male sex hormones) are important for growth/maintenance of muscle and bone. The classical
action of androgens is to bind the androgen receptor (AR) and regulate target genes. They can also act via nonclassical AR mechanisms through other cellular pathways. To understand the role of non-classical actions in
the musculoskeletal system we will study mice in which androgens can only act via this pathway. This
knowledge is important for the treatment of osteoporosis and muscle wasting.
Research achievements (from final report):
This study investigated the mechanisms through which male sex hormones (androgens) act. Androgens
normally act through the androgen receptor, a key-lock mechanism required to make particular cells responsive
to androgens, which controls other genes to be switched on or off. Our study used a mouse line in which we
created a mutant version of the androgen receptor that cannot directly regulate other genes. We showed that
mutant male mice have alterations in body weight and weight of the kidney, spleen and muscle and decreased
bone mass. In contrast, mutant female mice had altered kidney, spleen and heart weight and reduced bone
growth. This proves that androgens act in males via the direct gene regulation pathway to control kidney,
spleen, muscle and bone development. This also shows that male sex hormones also play an important role in
females to control kidney, spleen, heart and bone development. We also showed that treatment of mutant male
mice with male sex hormones decreased their bone size, proving that male sex hormones also act through other
mechanisms that do not involve direct gene regulation, to modify bone development. This research has
identified new pathways for male sex hormone action in both males and females. Understanding these actions
completely will open up new pathways for drug design to target these actions. This may allow the development
of more effective and specific therapies for the treatment of osteoporosis, a highly prevalent disease of the
aging population, and a number of conditions associated with reduced muscle mass, including chronic disease
and age-related frailty.
Expected future outcomes:
Results from continued research in this area will identify further actions of male sex hormones that occur via
novel mechanisms that do not involve direct gene regulation, including studying bone, muscle, fat and brain in
further detail. This knowledge may contribute to the development of novel treatments for osteoporosis, muscle
wasting and obesity.
Name of contact:
Helen Maclean
Email/Phone no. of contact:
hmaclean@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 558418
CIA Name: Dr Gerald Quan
Admin Inst: University of Melbourne
Main RFCD: Surgery
Total funding: $358,605
Start Year: 2009
End Year: 2013
Grant Type: Early Career Fellowships (Overseas)
Title of research award:
Multidisciplinary management of vertebral metastases identification of standardized surgical
guidelinesMultidisciplinary management of vertebral metastases identification of standardized surgical
guidelines
Lay Description (from application):
The spine is the commonest site of cancer spread to the skeleton and often leads to severe pain and paralysis.
Recent advances in surgical techniques enable removal and reconstruction of all tumours of the spine.
However, surgery remains controversial because of the need to weigh up the patient’s estimated length of
survival with the risks of surgery. Our aims are to develop clear guidelines on which patients to perform
surgery on, and what type of surgery to perform.
Research achievements (from final report):
My clinical research has shown prospectively that surgery can improve pain, function and quality of life in
selected patients suffering from symptomatic vertebral metastases. There was a highly significant improvement
in physical, role, cognitive and emotional functioning andglobal health status post-operatively. Greatest
improvement occurred in the early post-operative period and was maintained until death or during the 12
month prospective follow-up period. Multivariate analysis showed that independent prognostic factors for
survival after spinal metastases include primary tumour type, Karnofsky functional status, ASA score and
pain.These research findings have been translated into providing a clinical service that specializes in spinal
cancer and has led to the establishment of a Spinal Surgery Unit (Austin Health) protocol for surgical
management of vertebral pathological fractures and metastatic epidural spinal cord compression.Furthermore,
my NHMRC post-doctoral Fellowship has enabled me to establish from scratch the Spinal Biology Research
Laboratory, University of Melbourne Department of Surgery, Austin Health. This is a basic science laboratory
focussed on the molecular mechanisms behind growth of cancer in the spine, epidural spinal cord compression
by cancer, and the evolving neurological deficit and paralysis that ensues. I have established a novel in vivo
mouse model of human intraosseous spinal cancer that is induced by a percutaneous orthotopic inoculation of
human breast or prostate cancer cells into the upper lumbar vertebra of nude mice. This causes a reproducible
and evolving neurological decline resulting in eventual paraplegia that precisely resembles the human
condition of epidural spinal cord compression by cancer.
Expected future outcomes:
Future outcomes include continuing the provision of clinical specialist spinal surgical services to patients
suffering from spinal cancer and investigating in my basic science Laboratory the molecular mechanisms
behind growth of cancer in the spine and novel therapies.
Name of contact:
Gerald Quan
Email/Phone no. of contact:
gerald.quan@austin.org.au
NHMRC Research Achievements - SUMMARY
Grant ID: 566607
Start Year: 2009
CIA Name: Dr Patrick Humbert
End Year: 2012
Admin Inst: University of Melbourne
Grant Type: Career Development Fellowships
Main RFCD: Cell Development (incl. Cell Division and Apoptosis)
Total funding: $428,603
Title of research award:
Understanding the regulation of cell polarity in development and cancerUnderstanding the regulation of cell
polarity in development and cancer
Lay Description (from application):
Cell polarity is the property of cells to be spatially oriented in a tissue or organ. We have now shown that the
gene Scribble, a key regulator of cell orientation, may keep tumour development in check. In this proposal, we
will examine how disruption of Scribble and associated molecules affects normal development and promotes
cancer using a combination of tissue culture studies and a newly established mouse model. These studies may
provide novel targets for therapeutic intervention in cancer.
Research achievements (from final report):
Cell polarity is the property of cells to be spatially oriented in a tissue or organ. We have now shown that the
gene Scribble, a key regulator of cell orientation, may keep tumour development in check. In this proposal, we
examined how disruption of Scribble and associated molecules might affect normal development and promote
cancer using a combination of tissue culture studies and a newly established mouse model. We have
established in vivo using Genetically Engineered Mouse Models (GEMM) of Cancer that cell polarity genes
such as Scribble can behave as tumour suppressor genes in the Lung, Breast, Prostate and Skin epithelial
compartment. In many of these contexts, loss of Scribble leads to upregulation of sustained MAPK signalling
and appears to drive many of the phenotypes and pathology observed. Thus Scribble is a novel regulator of the
Ras-MAPK pathway, a central driver of tumour invasion and cancer progression. We also conducted a large
scale RNAi screen and identified a large network enriched for polarity genes that is required for Scribble to be
able to suppress oncogenic Ras. These experiments have revealed that this extensive Cell polarity network can
act as tumour suppressor process and controls both MAPK and cell polarity in vivo and in human tissue to
suppress tumour progression. These studies may provide novel targets for therapeutic intervention in cancer.
Expected future outcomes:
Further understanding of how loss of architecture can occur and impact on cancer progression should lead to
the discovery of novel prognosis factors, novel chemotherapeutic targets as well as a better understanding of
prostate biology and cancer progression.
Name of contact:
Patrick Humbert
Email/Phone no. of contact:
patrick.humbert@petermac.org
NHMRC Research Achievements - SUMMARY
Grant ID: 566621
CIA Name: Prof Seong-Seng Tan
Admin Inst: University of Melbourne
Main RFCD: Cellular Nervous System
Total funding: $836,225
Start Year: 2009
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
Neuroprotection by Ndfip1 in brain injury - identifying targets and understanding mechanismsNeuroprotection
by Ndfip1 in brain injury - identifying targets and understanding mechanisms
Lay Description (from application):
Brain injury from trauma and motor vehicle accidents is a serious health issue, affecting approximately 30,000
Australians per year. About 10% of the victims suffer serious long term consequences, including mental,
physical and behavioural impairment. We have discovered a new brain protein capable of preventing neurons
from dying following injury. This grant will improve our understanding of how this protein works, and
provide a scientific foundation for devising therapies.
Research achievements (from final report):
We discovered a natural protein in the brain that can be turned on to defend neurons against death after injury.
This new protein, called Ndfip1, is strongly switched on in brain cells after stroke or traumatic brain injury in
humans, and also in mice after brain injury. We found that if Ndfip1 is strongly switched on, then injured
neurons can survive the stress episode. A major aim of the grant was to understand how Ndfip1 is able to
defend neurons against death. This aim was successfully achieved by our studies identifying at least two
mechanisms. (1) Ndfip1 is able to temporarily shut off entry of toxic metals into brain cells that can otherwise
poison the neurons. We identified that Ndfip1 is able to off the metal transporter DMT1 during brain injury,
therefore limiting metal entry into nerve cells. (2) Ndfip1 is able to hijack Pten, an anti-cancer protein in the
cell, to defend brain cells. Ndfip1 achieves this by moving Pten into the cell nucleus, therefore quarantining the
anti-survival effects of Pten. Finally, we were also successful in manufacturing a drug that in principle, can
increase Ndfip1 in nerve cells. This drug is subjected to a patent application. All together, our studies provide
real foundations for identifying drugs that can increase Ndfip1 to increase brain cell survival after brain injury
and stroke.
Expected future outcomes:
We expect to create more drugs that can increase Ndfip1 on demand in brain cells. This research will provide
strong foundations for therapeutic drug design. In addition, we are excited at the possibility that Ndfip1 might
be a key lever for controlling brain tumours by its ability to control the cancer protein PTEN.
Name of contact:
Professor Seong-Seng Tan
Email/Phone no. of contact:
sst@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 566626
CIA Name: Prof Jane Pirkis
Admin Inst: University of Melbourne
Main RFCD: Mental Health
Total funding: $580,752
Start Year: 2009
End Year: 2013
Grant Type: NHMRC Research Fellowships
Title of research award:
Uncooupled Research FellowshipUncooupled Research Fellowship
Lay Description (from application):
I am a psychologist and epidemiologist working in the field of suicide prevention. I am proposing a program of
work that will systematically evaluate a range of suicide prevention initiatives for particular at-risk groups
using novel evaluation methodolog
Research achievements (from final report):
My Fellowship aim was to evaluate a range of suicide prevention initiatives using standard and novel
evaluation methodologies. I have evaluated universal interventions designed to reduce suicide at suicide
hotspots, prevent and/or contain suicide clusters, improve media reporting of suicide. I have also conducted
system-level analyses of programs designed to prevent suicide and/or improve mental health (e.g., the suicide
prevention component of the Access to Allied Psychological Services program, Lifeline, a project aimed at
reducing suicides at Gap Park). I am currently leading a trial examining the effectiveness of community service
announcements in preventing suicide among young people, and am supervising a PhD student who is
conducting a trial of an online, CBT-based intervention for young people. In addition to this, I have continued
my descriptive work on completed and attempted suicide (e.g., publishing epidemiological studies on suicide
by occupation and suicide clusters, and analyses on reporting of suicide locally and internationally).
Expected future outcomes:
My work has produced tangible outcomes in terms of suicide prevention efforts. For example, my work on
interventions at suicide hotspots has led to various local and internation enquiries about, for example, how to
go about constructing barriers on bridges. I anticipate that these sorts of community-relevant outcomes wil
continue.
Name of contact:
Caitlin Moffat
Email/Phone no. of contact:
Caitlin.Moffat@woollahra.nsw.gov.au
NHMRC Research Achievements - SUMMARY
Grant ID: 566783
Start Year: 2009
CIA Name: A/Pr Paul McCrory
End Year: 2013
Admin Inst: University of Melbourne
Grant Type: NHMRC Project Grants
Main RFCD: Complementary-Alternative Medicine not elsewhere classified
Total funding: $701,120
Title of research award:
Laser acupuncture in patients with chronic knee pain: a randomised placebo-controlled trialLaser acupuncture
in patients with chronic knee pain: a randomised placebo-controlled trial
Lay Description (from application):
Chronic knee pain is a common and disabling musculoskeletal condition that causes a loss of functional
independence and results in significant health care costs. In the majority of patients the most common cause is
osteoarthritis. Acupuncture is a form of non-surgical treatment commonly sought by patients and often
recommended by GP's. The main outcomes from our project are to establish the role, clinical effectiveness and
cost benefit of laser and needle acupuncture in knee pain patients.
Research achievements (from final report):
Knee pain is a common, chronic musculoskeletal condition or which arthritis is the major cause in older adults.
'Arthritis' has been identified by the Government as one of its priority health areas. Acupuncture may be
effective in relieving knee pain, and laser acupuncture has the potential to be as effective or superior to needle
acupuncture. Our project compared the efficacy of needle acupuncture, laser acupuncture, and sham laser
acupuncture to a natural history cohort who did not receive acupuncture. We have completed a large Zelendesign randomised controlled trial in order to answer this question. We have published the protocol for this
clinical trial and are about to commence analysing the data to determine the study findings. This work has
potential to be published in the highest impact literature in the field. The findings will contribute to the
formulation of evidence-based clinical guidelines for rehabilitation of knee OA and will impact the clinical
practice of healthcare professionals (particularly physiotherapists) who manage patients with knee pain.
Expected future outcomes:
We are about to analyse the data from our completed clinical trial. We expect to publish the findings in a major
medical journal, as well as present at multidisciplinary conferences. Our results will influence future clinical
guidelines and clinical practice.
Name of contact:
A/Prof Paul Mccrory
Email/Phone no. of contact:
paulmccrory@icloud.com
NHMRC Research Achievements - SUMMARY
Grant ID: 566916
CIA Name: Prof Ego Seeman
Admin Inst: University of Melbourne
Main RFCD: Endocrinology
Total funding: $620,381
Start Year: 2009
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
Bone Fragility: The Neglected Role of Cortical PorosityBone Fragility: The Neglected Role of Cortical
Porosity
Lay Description (from application):
Cortical (outer shell) or compact bone constitutes 80% of the skeleton. It is not solid as implied by its name
but made of inter-connected canals resembling a network of roads. We recently discovered that most of the
bone loss with age occurs from these canals, not from t rabecular bone as currently believed. This suggests to
know why and how bone breaks requires the study of the morphology of these canals and how they change
with age. This is what we propose to do. It has never been done.
Research achievements (from final report):
, About 75% of all fractures in the community occur in women with bone density values above the osteoporosis
range. These individuals will not be offered treatment and so will go on to sustain fractures. There is therefore
an urgent need to develop tests that allow better identification of individuals at risk for fracture. Measurement
of porosity (i.e., holes in the bone) is a prime candidate because the higher the porosity, the more fragile the
bone independent of its density. The aim of this grant was to(i.) define the 3D morphology of pores (ii.) define
changes in tporosity associated with ageing . (iii.) Use the information obtained to build a software that
measures this porosity in clinical settings; and can be used a diagnosis test., , We reported that increase in
porosity was responsible for 70% of the total bone loss during ageing and this was poorly captured by the bone
density test. This work was published in The Lancet. It is highly cited and has played a key role in driving the
bone medical community interested in cortical porosity. , , Knowledge of the morphology network of pores has
led to discovery of a method and system for quantification of porosity in clinical settings. The method is
patented and reached the national phase in key countries including the USA, EU, Australia, Japan, China, and
India. The software implementing the method has been developed and is now used to quantify porosity in
individuals worldwide including USA and Australia, .
Expected future outcomes:
We expect that the porosity measurement develop with the support of this grant will become a routine clinical
test for bone diseases; allowing to better identify individuals at risk for fracture in clinics, better monitor the
effect of diseases and treatment on bone. This will reduce disease burden with major social and economic
benefits.
Name of contact:
Roger Zebaze
Email/Phone no. of contact:
zebaze @unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 568850
CIA Name: A/Pr James Brock
Admin Inst: University of Melbourne
Main RFCD: Autonomic Nervous System
Total funding: $390,886
Start Year: 2009
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
Do postjunctional alterations explain the effects of diabetes on neurovascular transmission?Do postjunctional
alterations explain the effects of diabetes on neurovascular transmission?
Lay Description (from application):
Diabetes produces disordered skin blood flow that increases risk of skin ulcers and gangrene. The project
investigates nervous control of skin blood vessels in diabetes. It is assumed that all affects of diabetes on nerve
function are explained by loss of nerves. We hypothesize that some affects of diabetes are due to dysfunction
of blood vessels and not to nerve loss. The objective is to identify drug targets to improve blood flow in skin
and thereby reduce the risk of skin ulcers and gangrene.
Research achievements (from final report):
The primary achievement of this study is the establishment of an animal model for investigating the effects of
diabetes on the nerves (sympathetic nerves) that control blood vessels. Specifically the project has identified
that diabetes produces changes in the structure and chemistry of sympathetic nerve terminals in a small artery
that supplies blood to skin. While it is widely believed that diabetes can damage sympathetic nerves, to our
knowledge this is the first study to directly demonstrate that diabetes affects sympathetic nerves supplying
arterial blood vessels. Importantly, these changes were seen in an artey supplying blood to skin where diabetes
is known to impair nerve-mediated control of blood flow. The effects of diabetes on sympathetic nerves
controlling arteries that supply blood to the intestine were also investigated but these were not affected by
diabetes. The new model will provide opportunities to test drugs that prevent or reverse diabetes-induced nerve
damage.
Expected future outcomes:
The viability of this model for testing neuroprotective agents needs to be further assessed. Ideally we would
like to do this with Industry support and will investigating this possibility in the near future.
Name of contact:
James Brock
Email/Phone no. of contact:
j.brock@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 570877
CIA Name: Prof Janet Keast
Admin Inst: University of Melbourne
Main RFCD: Autonomic Nervous System
Total funding: $393,278
Start Year: 2009
End Year: 2013
Grant Type: NHMRC Project Grants
Title of research award:
Modulation of autonomic nerve growth by guidance factorsModulation of autonomic nerve growth by
guidance factors
Lay Description (from application):
Our goal is to understand how adult nerves are affected by injury so that we can devise therapies to make them
regrow better. We will focus on nerves that control the urogenital organs because these are often injured during
surgical procedures (e.g. prostatectomy, hysterectomy), with devastating effects on patients' quality of life. In
this project we will investigate how naturally-occurring growth-inhibitory molecules affect nerve regrowth
after injury in the pelvic nervous system.
Research achievements (from final report):
Nerves that control the urogenital organs are often injured during pelvic surgery as it is almost impossible to
completely avoid these nerves during removal of tumours (e.g. during prostatectomy). This often leads to
bladder and sexual dysfunction. During development, proteins called guidance factors are secreted by tissues
and provide directions to new axons so that they grow to their correct targets. Here we studied a naturally
produced guidance factor called semaphorin 3A (sema 3A) and found that it can block the growth of axons in
adult pelvic neurons. This means that if we could block sema 3A actions, we could potentially promote nerve
regrowth after injury. During this study we also discovered how some naturally occurring nerve growth factors
stimulate adult neurons, and found an unexpected link between testosterone and the neurotrophic factor,
neurturin. Together, these studies we have found new ways for controlling growth in pelvic neurons and may
lead to new strategies for promoting repair.
Expected future outcomes:
We now plan to conduct studies in vivo to alter sema 3A levels or exposure to other growth factors, in order to
optimise the conditions for axon regrowth. In combination with other research being conducted in this area, we
hope this will lead to a new treatment to maximise nerve regrowth after injury.
Name of contact:
Prof Janet R Keast
Email/Phone no. of contact:
jkeast@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 628422
CIA Name: A/Pr Kerrie Sanders
Admin Inst: University of Melbourne
Main RFCD: Orthopaedics
Total funding: $411,628
Start Year: 2010
End Year: 2012
Grant Type: NHMRC Project Grants
Title of research award:
The Australian Study of Cost and Utilities Related to Osteoporotic FracturesThe Australian Study of Cost and
Utilities Related to Osteoporotic Fractures
Lay Description (from application):
The research will quantify the cost and quality of life impact of fragility fractures in Australia. The study
design is based on an international study - International Costs and Utilities Related to Osteoporotic Fracutres
Study (ICUORS) that aims to investigate the impact of osteoporosis-related fractures of the hip, spine and
wrist. Results can be used to compare cost-effectiveness of different drugs and lifestyle interventions aiming to
decrease the burden of osteoporosis in Australia.
Research achievements (from final report):
This project is a health economics study on fragility fractures in Australia. Using uniform methodology this
study, being conducted at eight teaching hospitals across Australia, will establish both 'quality of life' loss and
monetary cost of low trauma fractures in older adults. The study design is based on an international Swedish
study. This standardised methodology will facilitate international comparisons. The results will be used to
establish the true burden of osteoporosis in Australia and in future cost-effectiveness analysis. Future
researchers will be able to access this data to demonstrate that new interventions improve the quality of life and
minimize cost in the prevention and treatment of fragility fracture patients. The results to date are already being
used by Osteoporosis Australia to identify and highlight the under-recognised burden of fragility fractures in
this country.
Expected future outcomes:
Results are generating data on the type of services patients use when they sustain a low trauma fracture
including medical and inpatient services, use of allied health as well as comunity and family assistance.
Participants also complete quality of life questionnaires at intervals up to 18 months following the fracture. The
major fractures are hip, vertebral and wrist..
Name of contact:
A/Prof Kerrie Sanders
Email/Phone no. of contact:
ksanders@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 628701
CIA Name: Prof Ego Seeman
Admin Inst: University of Melbourne
Main RFCD: Endocrinology
Total funding: $865,474
Start Year: 2010
End Year: 2012
Grant Type: NHMRC Project Grants
Title of research award:
Fragility Fractures: The Neglected Role of Cortical PorosityFragility Fractures: The Neglected Role of Cortical
Porosity
Lay Description (from application):
We just discovered that bone lost with age occurs mostly from pores within the cortex (outer shell) of the bone;
These pores become larger (porosity) making bones fragile. This process is poorly detected by bone density
(currently used tool) so that most people with weak bones are missed. To address this issue, we have for the
first time, develop a technology to accurately quantify porosity in living peoples. With teams around the
world, we aim here to fill this gap in the diagnosis.
Research achievements (from final report):
Bone mineral density (BMD) the test commonly used in clinical and research settings to identify individuals at
risk for fracture. This test is neither sensitive nor specific; most people diagnosed by BMD as at risk for
fracture never sustain a sustain a fracture, and most (~70%) of all fracture occur in people with BMD higher
than the range defining osteoorosity. To prevent fractures the important challenge is to identify the majority of
people with normal BMD who sustain a fracture., Our first study measureing porosity of bone was published in
the Lancet. This identified porosity as a main consequence of bone loss and weakness of bone. This now
provides a test to identify people at risk for fractures missed by BMD. The grant provided by the NHMRC
helped us develop and validate a computer program that automatically measures this porosity in clinical
settings. This program called StrAx1.0 is now widely recognised and we are collaborating with many
investigators in Australia, Europe and USA applying this method. Several studies are now published and the
most recent identifies women at risk for forearm fractures not identified using bone densitometry. this provides
clinicians with useful information helping them decide who to treat and not treat . This has been confirmed in
two separates groups of women in Australia and USA. The work is in review at a top medical journal at this
time.
Expected future outcomes:
Measuring porosity will become a rountine test helping doctors identify patients needing therapy and will help
to determine if treatment is successful by reducing porosity.
Name of contact:
Roger Zebaze
Email/Phone no. of contact:
zebaze@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 628799
Start Year: 2010
CIA Name: A/Pr Helmut Butzkueven
End Year: 2012
Admin Inst: University of Melbourne
Grant Type: NHMRC Project Grants
Main RFCD: Neurology and Neuromuscular Diseases
Total funding: $516,305
Title of research award:
Validating novel serum markers of neurodegeneration in Multiple Sclerosis patients.Validating novel serum
markers of neurodegeneration in Multiple Sclerosis patients.
Lay Description (from application):
In multiple sclerosis (MS), permanent disability occurs when brain cells known as neurons are damaged
following an immune attack. Current treatments reduce the number and severity of immune attacks, but they do
not prevent neuron damage or permanent disability in many patients. There is currently no direct way to
measure neuron damage in humans, so it is difficult to develop new drugs to prevent it. To address this need,
we will trial a new blood test for measuring neuron damage in MS patients.
Research achievements (from final report):
Our research aims to develop a bllod test for the extent of brain injury in Multiple Sclerosis. Specifically, we
are targeting the detection of componenets of dead and injured nerve cells and their cables (axons) that can be
found in very low levels in the blood. Axon injury and loss are believed to be the main reason why some
people with MS develop progressive disability, so that a test to detect this directly could help in selecting the
most appropriate treatment for patients and allow better outcome prognosis. Our results show that
approximately 9% of relapsing-remitting MS patients and 30% of secondary progressive MS patients have
higher than normal blood levels of pNF-H (pNFH positive), and that the patients who are "pNFH positive" are
more severely affected. In this research, we have therefore been able to take first steps to developing this new
test, which we hope will ultimately become available for geenral use to aid the management of people with MS
and perhaps becoem a tool to detect axon and nerve cell damage at a time when it can still be reduced or
prevented.
Expected future outcomes:
We are currently completing the major final manuscript relating to the data. We hope that this publication
could provide the impetus for discussion with major MS pharmaceutical companies to test serum collected in
drug trials for the pNFH signal, which would be a critical step for clinical translation, ie. transition form
research assay to one that might be avaialble in clinical practice.
Name of contact:
Helmut Butzkueven
Email/Phone no. of contact:
butz@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 1004938
CIA Name: Prof Ego Seeman
Admin Inst: University of Melbourne
Main RFCD: Endocrinology
Total funding: $873,951
Start Year: 2011
End Year: 2013
Grant Type: NHMRC Project Grants
Title of research award:
The micro-structural basis of bone loss and fragility after menopause: a longitudinal co-twin control studyThe
micro-structural basis of bone loss and fragility after menopause: a longitudinal co-twin control study
Lay Description (from application):
Every woman becomes postmenopausal. Not all lose bone or sustain fractures after menopause. We will
identify women who lose bone and those who don't and so identify women at risk for fracture so that they can
be targeted for treatment and identify those who do not need to be treated. This will be done by measuring
bone structure and how strong the bone is using a new, safe, quick technology that can be used in clinical
practice
Research achievements (from final report):
Bone loss is a most important cause of bone fragility. To identify women who lose bone after menopause and
those who do not, in a prospective cotwin control study, we have (i) assessed genetic and environmental
contributions to variance in bone microstructure (ii) determined causes of bone loss by comparing cotwin
differences in structure vs cotwin differences in remodelling markers (iii) examined the contribution of
differences in cortical porosity, area and tissue mineral density, trabecular architectural decay to fracture risk in
a case-control study. Bone structure, remodelling and strength at baseline and their relationship have been
quantified during 3 years (changes in cortical porosity, trabecular number and thickness, loss of strength) using
high-resolution 3-D pQCT in 320 female twin pairs aged 25 to 75 years old in Melbourne area. Analysis
followed the classical twin model, using a generalised estimating equation and logistic regression. Our
prospective data demonstrated that cortical porosity increased and trabecular BV/TV decreased confirming the
accelerated loss of bone during menopause. Women enter menopause with high cortical porosity and bone
remodelling markers would be at high risk to lose bone and also sustain fractures.
Expected future outcomes:
To provide a clinical tool to accurately identify those at risk who lose bone and those who don't to correctly
target treatment to individuals who need it and avoid unnecessary treatment of individuals unlikely to sustain
fractures.
Name of contact:
Ego Seeman
Email/Phone no. of contact:
egos@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 1006077
CIA Name: Prof Terence O'Brien
Admin Inst: University of Melbourne
Main RFCD: Central Nervous System
Total funding: $524,820
Start Year: 2011
End Year: 2013
Grant Type: NHMRC Project Grants
Title of research award:
Targeting Tau phosphorylation to treat and prevent acquired epilepsy, neurodegeneration and neuropsychiatric
disease following a brain injuryTargeting Tau phosphorylation to treat and prevent acquired epilepsy,
neurodegeneration and neuropsychiatric disease following a brain injury
Lay Description (from application):
This project will explore a new approach to the prevention and treatment of epilepsy and the associated mental
health disorders following a brain injury. This involves inhibiting pathological forms of the Tau protein, which
has been implicated in the development of epilepsy and neurodegeneration. The drug that will be tested in this
study has already been demonstrated to be safe and well tolerated in humans, meaning that a positive result
from these studies could be expediently translated into clinical studies.
Research achievements (from final report):
Epilepsy is a common and disabling consequence of a brain injury, and is often associated with significant
mental health, cognitive and degenerative brain changes. There is currently no available treatment that is
effective in protecting against the development of epilepsy and its associated problems. This project
investigated the efficacy of an entirely novel intervention, sodium selenate, which inhibits the pathological
accumulation of the a toxic form of the brain protein, tau., The study aimed to establish: (i) Whether sodium
selenate is effective at suppressing spontaneous seizures in animals with acquired epilepsy; (ii) Whether
treatment with sodium selenate is effective at inhibiting epileptogenesis, neurodegeneration, and behavioural
disturbances following a range of acquired brain insults in rat models; (iii) To examine whether epilepsy
inducing brain insults results in altered levels of expression of Tau, its neurotoxic form, phospho-tau, and
PP2A in transgenic mouse strains, and whether treatment with selenate mitigates these changes., The results
demonstrated that treatment with sodium selenate was effective in suppressing spontaneous seizures in animals
with established acquired epilepsy. We further demonstrated that treatment with sodium selenate was effective
at inhibiting the development of epilepsy and the associated behavioural, cognitive and degenerative brain
changes when administered following a brain injury. In addition we found that treatment with sodium selenate
administered following a brain injury was effective in preventing the brain molecular changes related to the
neurotoxic form of tau that occur in animals that have developed epilepsy following a brain injury., This study
provides strong preclinical evidence for the efficacy of a novel approach to prevent the development of
epilepsy and the associated mental health, cognitive and degenerative brain changes following a brain insult.
Expected future outcomes:
This study established a new paradigm for assessing the effectiveness of an intervention on the development of
epilepsy, and also its associated neurodegeneration, neurobehavioural and neurocognitive deficits, following a
brain injury by performing serial in-vivo assessments complimented by terminal tissue level analysis.
Name of contact:
Terence O'brien
Email/Phone no. of contact:
obrientj@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 113811
CIA Name: Dr Hala Zreiqat
Admin Inst: University of New South Wales
Main RFCD: Biomaterials
Total funding: $273,429
Start Year: 2000
End Year: 2002
Grant Type: NHMRC Project Grants
Title of research award:
Peptides Bound to Commonly Used Orthopaedic and Dental Biomaterials:In Vitro and in Vivo Effect on
Osteogenesis.Peptides Bound to Commonly Used Orthopaedic and Dental Biomaterials:In Vitro and in Vivo
Effect on Osteogenesis.
Lay Description (from application):
In 1992, the orthopaedics industry fitted some 300,000 prosthetic devices, artificial hips, knees, giving this
industry a global market of $2.1 billion with a projected market growth exceeding 10% per annum. In (1994/5)
5,717 prosthetic hips and 4,593 knees were surgically implanted in NSW of which 14% of hips and 9.5% of
knees were revisions. Considerable health funding is allocated to joint replacement for the nation, although
successful, outcomes are finite. Importantly, and aside from costs, patients morbidity is high.
The major
cause of long-term failure of these prosthetic replacements is aseptic loosening, the result of bone loss at the
bone/device interface. Novel approaches to development of more efficient implant materials would ultimately
lead to major contributions to the mobility and and quality of life for these patients. Considerable effort has
been devoted to alter surface characteristics of orthopaedic implants to improve the interlocking of device and
skeleton. We were the first to demonstrate that surface chemical modification of biomaterials using selected
ions resulted in an enhanced bone formation. This proposal is aimed at chemically modifying the surfaces of
commonly used orthopaedic and dental materials, to improve the biocompatibility of new devices and the
surface coatings for existing prostheses. Furthermore, this application will build on the in vitro data showing
that particular peptides specifically bind osteoblasts and therefore have the potential to provide a surface on a
prosthesis that is conducive to bone formation. To date, we have coupled these peptides to metallic surfaces
and will proceed to study the osteoblastic phenotype and subsequent osteogenesis. Development of these novel
biocompatible surfaces is anticipated to reduce patient morbidity and result in significant health care savings.
Research achievements (from final report):
N/A
Expected future outcomes:
The project has the potential to improve the binding qualities of prostheses, thus reducing the rate of revision
arthroplasty. This would lead to a significant reduction in the cost of health care in an aging population.
National benefits of this project include:, 1.
Development of new implant
material with improved bony integration., 2.
Improved quality of life for recipients
of prosthetic devices. , 3.
Provide guidelines for the design
and/or surface modification of orthopaedic/dental biomaterials., 4.
Itemize strategies to improve longterm fixation of prostheses., Knowledge and expertise gained will facilitate the optimization of various implant
materials for orthopaedic and implant dentistry, and thus will promote the technology transfer from academia
to the relevant medical device industry., It is expected that some of the outcomes will generate IP, which would
initiate negotiations towards improved commercial devices.
Name of contact:
Dr Hala Zreiqat
Email/Phone no. of contact:
N/A
NHMRC Research Achievements - SUMMARY
Grant ID: 157019
CIA Name: Prof David Tracey
Admin Inst: University of New South Wales
Main RFCD: Sensory Systems
Total funding: $196,018
Start Year: 2001
End Year: 2003
Grant Type: NHMRC Project Grants
Title of research award:
Mechanisms of neuropathic painMechanisms of neuropathic pain
Lay Description (from application):
Disorders of pain sensation due to nerve damage are common, debilitating and difficult to treat. Nerve damage
often results in increased sensitivity to painful stimuli and the perception of innocuous stimuli as painful; it
may also result in spontaneous pain. Pain is one of the commonest clinical problems, and yet it is often
accepted or taken for granted. The outcome of this work will be an increased understanding of the way in
which nerve injury leads to spontaneous pain and increased sensitivity to painful stimuli. This will lead in turn
to the development of more effective treatments for neuropathic pain.
Research achievements (from final report):
Mast cells are part of the immune system often associated with asthma. There are resident mast cells in
peripheral nerves, and we showed that they play a key role in the chronic (neuropathic) pain which often results
from injury of peripheral nerves. We showed that stabilising mast cells with cromoglycate (an agent commonly
used to treat asthma) blocks the initiation of neuropathic pain in experimental animals. A role of histamine
(which is released by activated mast cells) was also demonstrated. These findings have potential significance
for pre-empting the development of neuropathic pain in patients where nerves are injured by surgery (for
example in thoracotomy).
Expected future outcomes:
We plan to carry out further work on the subtypes of histamine receptor which contribute to neuropathic pain.
This could lead to pilot clinical trials.
Name of contact:
David Tracey
Email/Phone no. of contact:
d.tracey@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 157063
Start Year: 2001
CIA Name: Prof Marcus Stoodley
End Year: 2003
Admin Inst: University of New South Wales
Grant Type: NHMRC Project Grants
Main RFCD: Neurology and Neuromuscular Diseases
Total funding: $344,442
Title of research award:
Investigations of cerebrospinal fluid flow in extracanalicular syringomyelia.Investigations of cerebrospinal
fluid flow in extracanalicular syringomyelia.
Lay Description (from application):
Cysts in the spinal cord (syringomyelia) develop in children and young adults with congenital spinal cord
abnormalities such as spina bifida, and in people of all ages after spinal cord injury or meningitis.
Syringomyelia causes pain and paralysis that usually does not improve even with treatment. The current lack
of knowledge about the mechanism of spinal cord cyst formation and enlargement is preventing the
development of effective therapy. We have previously shown that some types of spinal cord cysts enlarge by
the normal fluid surrounding the spinal cord being pumped around small arteries into the centre of the spinal
cord. The mechanism of enlargement of post-traumatic spinal cord cysts remains unknown, and this
debilitating type of syringomyelia remains difficult to treat. Our hypothesis is that post-traumatic spinal cord
cysts also enlarge by fluid being pumped into them around small arteries. A further hypothesis is that
reductions of arterial pulsations and of the pressure in the fluid surrounding the spinal cord will prevent or
inhibit cyst enlargement. These hypotheses will be tested by examining fluid flow in models of post-traumatic
syringomyelia in rats and sheep. We have established a model of post-traumatic syringomyelia in rats and the
first phase of the project will be to refine and characterize this model and to reproduce it in sheep. The second
phase will be to determine whether these cysts enlarge by a flow of fluid around small arteries that is driven by
arterial pulsations, as they do in other types of syringomyelia. The final phase will be to determine whether
reducing the pressure in the fluid around the spinal cord prevents cyst enlargement. Confirmation that these
techniques prevent cyst enlargement would open up new possibilities for the treatment of human
syringomyelia.
Research achievements (from final report):
This project investigating aspects of fluid flow in extracanalicular syringomyelia was completed in 2003. The
first phase involved refining the rodent model of post-traumatic syringomyelia and this was successfully
completed, with a technique developed that produces syrinxes in 100% of animals. Development of the sheep
model proved more complex, but a success rate of syrinx production of over 75% was achieved. Fluid flow
studies demonstrated that CSF enters extracanalicular syringes via perivascular spaces and also (to a lesser
extent) by a direct transparenchymal route. Flow into perivascular spaces is greater at levels adjacent to the
arachnoiditis than at other levels in the cord. Shunting CSF from the spinal subarachnoid space to the
peritoneum decreases perivascular flow in the brain, but does not affect the increased flow at the level of the
syrinx. Dr Andrew Brodbelt (a British neurosurgical trainee who interrupted his clinical training specifically to
work on this project) was awarded the prestigious Tow Prize at the Prince of Wales Hospital for the
presentation of this research work, and his PhD will be awarded in May 2004. This research has contributed to
our understanding of post-traumatic syringomyelia, which will lead to improvements in management of the
condition.
Expected future outcomes:
This research has contributed to our understanding of post-traumatic syringomyelia, which will lead to
improvements in management of the condition. We are continuing our research, focussing on the forces that
drive fluid from the subarachnoid space into the spinal cord.
Name of contact:
Marcus Stoodley
Email/Phone no. of contact:
NHMRC Research Achievements - SUMMARY
m.stoodley@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 209583
CIA Name: Prof Phil Waite
Admin Inst: University of New South Wales
Main RFCD: Central Nervous System
Total funding: $255,990
Start Year: 2002
End Year: 2004
Grant Type: NHMRC Project Grants
Title of research award:
Repairing the injured spinal cord: potential for human olfactory ensheathing cellsRepairing the injured spinal
cord: potential for human olfactory ensheathing cells
Lay Description (from application):
Spinal cord injury is a major cause of morbidity, particularly among young people involved in road accidents
and sports injuries. Finding ways to treat paraplegia is a major goal of neuroscience research. Recently, there
has been considerable interest in a special cell found in the olfactory system, the ensheathing cell, which has
been found to support regeneration in the spinal cord. Our laboratory has shown that injection of these
ensheathing cells into the completely cut spinal cord of adult rats can lead to limited functional recovery of
hindlimb movement. We used peripheral ensheathing cells because, in humans, such cells can be obtained
relatively easily and they reduce problems of tissue rejection. We found that peripheral cells are as effective as
previous reports using central ensheathing cells. Our overall aim now is to advance towards the use of olfactory
cells in human spinal cord injury, by trialing 3 procedures of clinical relevance: a) to test whether human
olfactory cells can also support functional recovery in rats. Human cells can be obtained from the nose by a
simple biopsy procedure. If they able to support regeneration, this will open the way for their use in autografts
in human paraplegia. b) to delay the time when the olfactory cells are applied to the injured cord. At present,
neurosurgeons are not be willing to treat the cord immediately after the injury, because of the risk of causing
further damage. This trial is designed to test whether delayed treatment is still effective. c) to test the
effectiveness of the cells after bruising, rather than cutting, the cord. Bruising is a more common type of injury
in people, hence it is necessary to know how these cells respond to this type of damage. These procedures
have been chosen to move our basic research closer to clinical application. Although treatment in humans is
still a long way off, these basic studies are essential if conditions like paraplegia are eventually to become
treatable.
Research achievements (from final report):
Spinal cord injury continues to be a major cause of morbidity, particularly among young people involved in
road accidents and sports injuries. Finding ways to treat paraplegia and quadriplegia is a major goal of
neuroscience research. Studies around the world have reported encouraging improvements in function in
animals models of spinal cord injury after transplants of a special support cell, the olfactory ensheathing cell
(OECs). Most of these studies have used OECs from rats and reported improvements in locomotion when
transplanted into injured rat spinal cord. , We have extended the basic data on the potential of OECs for clinical
e techniques for obtaining and culturing human OECs from simple
OECs in different types of spinal cord injuries (transections, contusions, dislocations) and different functional
normal and injured spinal cord, in a similar manner to that seen with rat OECs. They also cease proliferating,
hence eliminating complications from abnormal growths., These outcomes are significant in that they provide
essential baseline data on the properties and survival of human OECs. Such baseline data is a critical
preliminary for the use of OECs in patients after spinal cord injuries.
Expected future outcomes:
A safety and feasibility trial of human OECs in 3 spinal patients is already underway with one of our CIs (A,
M-S) in Brisbane. Once long term safety and feasibility of these transplants can be assured, the way will be
open for clinical trials to test efficacy in spinal patients.
Name of contact:
Prof Phil Waite
NHMRC Research Achievements - SUMMARY
Email/Phone no. of contact:
P.Waite@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 209632
CIA Name: A/Pr James Brock
Admin Inst: University of New South Wales
Main RFCD: Autonomic Nervous System
Total funding: $229,917
Start Year: 2002
End Year: 2004
Grant Type: NHMRC Project Grants
Title of research award:
Peripheral mechanisms involved in autonomic hyperreflexiaPeripheral mechanisms involved in autonomic
hyperreflexia
Lay Description (from application):
Bladder distension or minor unheeded injuries below the lesion in spinally injured people often lead to episodes
of high blood pressure that may cause stroke or death. These events require emergency hospitalization and are
expensive as well as dangerous. After spinal injury, the control of sympathetic nerves that supply arteries and
regulate blood pressure is lost. However, the nerves below the injury remain in place and the spinal cord below
the lesion contains connections that can activate them. Signals from the bladder or skin enter the remaining
lower part of the spinal cord and activate the sympathetic supply generating a rise in blood pressure. This
project will test the hypothesis that increased sensitivity of arteries to the chemicals released from the
sympathetic nerves leads to excessive vessel constriction, contributing to the exaggerated increase in pressure.
We will investigate arteries removed from rats with experimental spinal transection. We will test the
contractions of the arteries (a) to sympathetic nerve stimulation and (b) to the chemicals noradrenaline,
adenosine 5'-triphosphate (ATP) and neuropeptide Y that are normally released during nerve activity. We will
determine whether release of noradrenaline and ATP from nerves is normal or augmented using
electrochemical and electrophysiological techniques. We will compare the responses with those in normal
arteries, those in arteries whose nerves have been silenced by removing all connections from the spinal cord
and those in arteries that have lost all their nerve supply. This will enable us to identify whether the
mechanisms for release of transmitter substances are modified and whether the arterial muscle is hypersensitive
to these substances. The results will help in the design of safer treatment for these potentially lethal
emergencies in spinal patients.
Research achievements (from final report):
Bladder distension or minor unheeded injuries below the lesion in spinally injured people often lead to episodes
of high blood pressure (autonomic dysreflexia) that may cause stroke or death. These events require emergency
hospitalization and are expensive as well as dangerous. The project investigated whether an increase in the
response of arteries to nerve activation in two major vascular beds (splanchnic and cutaneous) can account for
the exaggerated vasoconstriction that underlies autonomic dysreflexia in patients with spinal cord injury. The
project demonstrated that: (1) Arteries from spinalized rats are much more readily activated by sympathetic
nerve stimulation; (2) The sympathetic nerve-mediated contractions of arteries from spinalized rats are larger
and abnormally prolonged; (3) In arteries from both intact and spinalized animals, sympathetic nerve-mediated
contractions are due almost entirely to the actions of released noradrenaline; (4) Arteries from spinalized rats
have an increased sensitivity to application of chemicals that mimic the effects of noradrenaline. These arteries
are also more readily contracted by other agents, suggesting the vascular muscle is generally more 'reactive'.
(5) Silencing the ogoing nerve activity by cutting the preganglionic axons (decentralization) produced similar
changes to those observed in arteries from spinalized animals, indicating that it is the decrease in nerve activity
following spinal transection that produces the increase in nerve evoked response. These changes in the
behaviour of arteries could play a major part in the dysreflexic episodes.
Expected future outcomes:
The experiments to date have demonstrated spinal injury can produce a major change in the response of arteries
to nerve stimulation. We now have to understand the underlying causes of this change. This knowledge will
allow us to propose new strategies for controlling/preventing autonomic dysreflexia.
Name of contact:
James Brock
NHMRC Research Achievements - SUMMARY
Email/Phone no. of contact:
j.brock@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 209633
CIA Name: Prof Stephen Lord
Admin Inst: University of New South Wales
Main RFCD: Geriatrics and Gerontology
Total funding: $610,500
Start Year: 2002
End Year: 2006
Grant Type: Established Career Fellowships
Title of research award:
Uncoupled Reseach FellowshipUncoupled Reseach Fellowship
Lay Description (from application):
Not Available
Research achievements (from final report):
My Fellowship ran in concert with the POPI Prevention of Injuries in Older People Partnership Grant
(www.powmri.edu.au/POPI) of which I was the Director. This major grant provided the foundation for my
research into falls injuries in older people. Major outcomes from this research include:, o
Two studies that
elucidated the mechanisms underlying impaired voluntary stepping in older people., o
A large RCT (n=
3,995) that examined interventions for preventing falls in older people when in hospital., o Six RCTs that
examined strategies for preventing falls in at-risk groups., o
Three studies which provided
objective findings about shoe features that maximise balance., o The development of both simple and
sophisticated fall risk assessment tools., o
A large prospective study that
identified cognitive and physiological risk factors for unsafe driving., Falls and fall related injury in older
people continue to challenge health and social care systems on a worldwide basis. The approaching impact of
fall related injury in Australia has been characterized as a potential future "epidemic" creating resource
demands that will be difficult to meet. The research undertaken enhances our understanding of strategies to
prevent falls, so as to address this important issue.
Expected future outcomes:
As a SPRF I am continuing research in the areas of falls risk factor identification and falls prevention
strategies. Work underway is examining falls risk factors in people with cognitive impairments and Parkinson's
disease; the development of fall risk screening tools and interventions for preventing falls in at-risk groups.
Name of contact:
Stephen Lord
Email/Phone no. of contact:
s.lord@powmri.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 222751
Start Year: 2003
CIA Name: Prof Elspeth McLachlan
End Year: 2005
Admin Inst: University of New South Wales
Grant Type: NHMRC Project Grants
Main RFCD: Neurosciences not elsewhere classified
Total funding: $378,300
Title of research award:
IMMUNE-MEDIATED INFLAMMATION IN DORSAL ROOT GANGLIA AFTER PERIPHERAL NERVE
INJURY AND IN SENSORY NEUROPATHIESIMMUNE-MEDIATED INFLAMMATION IN DORSAL
ROOT GANGLIA AFTER PERIPHERAL NERVE INJURY AND IN SENSORY NEUROPATHIES
Lay Description (from application):
Damage to the nervous system can occur because of accidental or iatrogenic trauma, toxins, infection,
metabolic disorders, and even normal ageing. The consequences can outweigh the direct effects of the injury.
Almost all injury to the nervous system results in loss of nerve cells and consequently modified sensation and
movement. Nerve damage may also be followed by sensory disturbances, ranging from tingling, numbness
and abnormal temperature sensations to spontaneous pain, allodynia (painful sensations from light touch) or
hyperalgesia (increased sensitivity to a damaging stimulus). Some of these symptoms are encountered in older
people as they lose sensory neurones. The problems are chronic and most are intractable to drugs. This project
will clarify how immune-mediated inflammation of dorsal root (sensory) ganglia (DRGs) contributes to these
sequelae. Even the simplest form of neural damage following peripheral nerve injury can produce changes in
regions of the nervous system far from the parts directly involved in the injury. Our recent work has described
for the first time the involvement of the immune system in triggering changes in DRGs following transection of
a distant peripheral nerve in rats. T-cell activation leads to invasion of macrophages and production of
proinflammatory cytokines. These substances can activate sensory neurones and may be responsible for
progressive neuronal death. Thus we have established a simple system in which we can evaluate the influx of
T-cells and macrophages of different kinds into DRGs after injury and other insults. We intend to use this to
define the sequence of cellular events involved in recruitment of immune cells and compare it with other
experimental interventions known to produce a neuroimmune response in this system. This will identify
whether the DRG is a special site for neuroimmune interactions and so should be a target for therapy.
Research achievements (from final report):
This project has advanced our knowledge about the body's response to damage of the peripheral nervous
system. Following injury of a major nerve trunk, usually in a limb, abnormal activity develops in sensory
pathways which can progress to chronic (neuropathic) pain through mechanisms that are not understood. Our
experiments have revealed details of the factors that determine how transection of the axons (processes) of
sensory nerve cells leads to inflammation around their cell bodies in sensory ganglia. We are trying to clarify
whether the role of the immune system is destructive or protective. We have characterized the inflammatory
process. Inflammatory cells release of substances that raise the excitability of sensory nerve cells and may
cause them to fire abnormally. We have also identified that some small sensory nerve cells of the type that
normally signal painful stimuli die after nerve injury more easily if they are surrounded by other damaged
nerve cells, and that inflammatory cells are involved in this process. The results are relevant not only to nerve
injury and neuropathies but also for other neurodegenerative disorders where axonal destruction leads to death
of the damaged neurones weeks to months later. For example, spinal cord injury may be followed by
continuing loss of function over many years. Understanding the contribution of inflammatory processes to
abnormal activity and neuronal death will enable the underlying mechanisms to be targetted and the causes of
chronic pain and functional loss after damage to the nervous system to be removed.
Expected future outcomes:
Many of our experiments are still being analysed and the results will be prepared for publication over the next
few months. These will describe the effects of a previous injury, how axonal injury signals to the immune
system and the effects of different injuries on the pattern of neuroinflammation.
Name of contact:
NHMRC Research Achievements - SUMMARY
Elspeth McLachlan
Email/Phone no. of contact:
e.mclachlan@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 222754
Start Year: 2003
CIA Name: Prof Skye McDonald
End Year: 2005
Admin Inst: University of New South Wales
Grant Type: NHMRC Project Grants
Main RFCD: Health, Clinical and Counselling Psychology
Total funding: $253,750
Title of research award:
Enhancing treatment effectiveness for psychosocial disorders after severe traumatic brain injuryEnhancing
treatment effectiveness for psychosocial disorders after severe traumatic brain injury
Lay Description (from application):
Motor vehicle accidents are a major cause of severe traumatic brain injury (TBI) leading to lifelong, crippling
disability. In NSW alone, there are approximately 770 new cases of severe brain injury each year. These people
require extensive inpatient rehabilitation and many go on to rely upon community resources for the rest of their
lives. The social and economic cost of such injury is cumulative. TBI is mainly experienced by young adults
(18-24 years of age) who have normal life expectancy and each year more casualties are added to this social
burden. Adults with TBI frequently experience a reduction in social skills. Loss of social skills presents major
obstacles to reintegration into the community by making the sufferer more taxing and less rewarding to interact
with socially. This loss of social skills limits their ability to maintain pre-injury relationships, and often creates
an off-putting first impression on potential new acquaintances that interferes with their ability to establish new
relationships. The following project is designed to develop and evaluate a treatment program to enhance the
TBI individual's ability to create a good first impression on meeting new acquaintances - e.g., potential
employers, work colleagues, customers, and social acquaintances - and to engage in behaviour that is mutually
rewarding. The project will inform current theoretical approaches to remediation, providing an examination of
the modifiability of social skills deficits that are the result of underlying cognitive impairments. It will provide
a systematic, integrated social skills treatment approach for both individuals and groups where there are
currently very few. The identification and refinement of successful treatment techniques will increase the
efficiency of brain injury rehabilitation in Australia, improve the quality of life for sufferers of TBI and their
families, reduce cost of rehabilitation and reduce reliance upon community resources in the long term.
Research achievements (from final report):
This project evaluated a new, three pronged approach to improving the social skills of adults with severe,
chronic brain injuries sustained as a result of trauma (e.g. motor vehicle accidents). Such injuries often cause
difficulties in cognition and behaviour and lead to longer term problems with social isolation, loss of self
esteem, depression and anxiety. To address this we developed a treatment program that included social skills
training, remediation of problems with social perception (e.g. reading emotions in others) and psychological
treatment for individual problems with self-esteem anxiety etc. This study used a randomised controlled trial
and recruited 51 participants who were allocated to treatment, social group (control condition) or waitlist. The
program included 12 weekly 3 hour group sessions and individual sessions with a clinical psychologist. It was
shown that treatment did improve social behaviour and social perception in those who received treatment
relative to those who remained on waitlist or who participated in a social group without specific therapeutic
content. Three manuals have been developed for clinical use: (1) a social skills treatment manual (2) a social
perception treatment manual (3) a manual for treating social anxiety. The results of the trial have recently been
prepared for publication. This is the first time a comprehensive treatment for social skills for people with
traumatic brain injuries has been evaluated and proven to be effective. It paves the way for better, evidence
based techniques in this much needed area of psychosocial rehabilitation.
Expected future outcomes:
This research will improve remediation of social skills in people with brain injuries and lead to better use of
evidence based practice. It will also be an impetus for further research into techniques to improve psychosocial
function in this and other clinical groups.
Name of contact:
Professor Skye Mcdonald.
NHMRC Research Achievements - SUMMARY
Email/Phone no. of contact:
s.mcdonald@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 300420
CIA Name: Prof James Colebatch
Admin Inst: University of New South Wales
Main RFCD: Central Nervous System
Total funding: $205,500
Start Year: 2004
End Year: 2006
Grant Type: NHMRC Project Grants
Title of research award:
Assessment of Vestibular Function and Balance in HumansAssessment of Vestibular Function and Balance in
Humans
Lay Description (from application):
This proposal focuses upon the function of the vestibular apparatus and the related problem of impaired
balance. The vestibular apparatus contains receptors which help us to maintain balance. Their clinical
assessment is difficult because they are small and lie deep within the skull. With previous NH&MRC support,
I have been able to develop a series of new tests to assess the function of the vestibular apparatus and these are
having significant clincal impact. Amongst the findings has been a clear demonstration that vestibular function
declines with age, starting relatively early.
This proposal builds upon the findings of the previous
application. Two main types of investigations are planned. In one a new technique of activating the vestibular
apparatus (localised skull vibration) will be used to study the brain areas that receive its signals ("evoked
potentials"). This will be the first time that it has been possible to study the connections between the balance
organs and the cortex of the brain in intact humans. I will apply the technique to patients with disturbed
vestibular function to improve our knowledge of how the brain adapts to disease of these organs. In the second
part of this study, a series of recordings will be done measuring sway under a variety of conditions both in
normal volunteers and in patients with some common disease states affecting balance. This should reveal new
information about both the factors that affect normal balance function and why balance is disturbed in these
diseases.
Research achievements (from final report):
This research project substantially increased our ability to measure the function of the vestibular apparatus
(balance organs) in normal humans and in disease states. Specifically the otolith component of the vestibular
apparatus was investigated, and this has been particularly difficult to assess in humans prior to the discovery of
our techniques. We have extended our earlier reports using clicks to other modalities. Many clinical diagnostic
laboratories both in Australia and overseas are now using these techniques to improve diagnosis and
management of a variety of vestibular (balance) disorders.
Expected future outcomes:
Further developments of these techniques is still occurring, including defining other pathways (to the eyes and
brain). These can be expected to further improve diagnosis and may also help to understand why some subjects
compensate in response to a vestibular (balance organ) disturbance while others do not.
Name of contact:
Prof James Colebatch
Email/Phone no. of contact:
j.colebatch@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 300437
CIA Name: A/Pr Lynne Bilston
Admin Inst: University of New South Wales
Main RFCD: Biomechanical Engineering
Total funding: $527,500
Start Year: 2004
End Year: 2008
Grant Type: Established Career Fellowships
Title of research award:
Uncoupled Research FellowshipUncoupled Research Fellowship
Lay Description (from application):
Not Available
Research achievements (from final report):
This fellowship has underpinned my research program, and allowed me to make significant research
discoveries and translate these into public policy. Key research findings from the fellowship period include: (a)
definition of the key factors underpinning injuries to children travelling in cars, and input into legislative
changes to require size-appropriate restraints for children in cars, and improvements in safety standards for
child restraints; (b) development of models of paediatric spinal cord injury that are able to reproduce the key
differences between paediatric and adult spinal cord injury, (c) development of novel imaging techniques to
measure soft tissue biomechanical properties, particularly for brain and muscle tissue.
Expected future outcomes:
The research conducted during this fellowship is expected to lead to new information on the mechanisms of
injury to children and other occupants of the rear seat of cars (currently being conducted), and preclinical
studies possibly leading to new diagnostic techniques bases on imaging of tissue stiffness.
Name of contact:
Lynne Bilston
Email/Phone no. of contact:
L.Bilston@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 350823
Start Year: 2005
CIA Name: Prof Caroline Finch
End Year: 2009
Admin Inst: University of New South Wales
Grant Type: Capacity
Main RFCD: Public Health and Health Services not elsewhere classified
Total funding: $2,351,750
Title of research award:
Addressing injury in a population health framework: An integrated approach to prevention, acute care and
rehabilitationAddressing injury in a population health framework: An integrated approach to prevention, acute
care and rehabilitation
Lay Description (from application):
In Australia, injury is the leading cause of death and disability in people aged under 55 years. It is also a major
cause of morbidity and mortality in older persons and, overall, accounts for a substantial proportion of acute
hospital services and long-term rehabilitation needs. This grant will build an internationally competitive
research team focused on reducing the public health burden of injury.
Research achievements (from final report):
This project supported the career development of 13 injury researchers whose collective research activity led to
>120 scientific publications/reports, >$7.4million in new research grants and >60 conference presentations.
Research findings were also instrumental in influencing injury prevention policy relating to roads, sport and
falls in older people.
Expected future outcomes:
The team Investigators have now established themselves as productive injury researchers. Several have their
own NHMRC Fellowship Support and others have moved on to research leadership positions of their own.
They are now placed to continue to conduct leading-edge injury research and to train the next generation of
young researchers.
Name of contact:
Professor Caroline Finch
Email/Phone no. of contact:
caroline.finch@monash.edu
NHMRC Research Achievements - SUMMARY
Grant ID: 350825
CIA Name: Prof Simon Gandevia
Admin Inst: University of New South Wales
Main RFCD: Sensory Systems
Total funding: $507,378
Start Year: 2005
End Year: 2007
Grant Type: NHMRC Project Grants
Title of research award:
Neural Mechanisms underlying Human ProprioceptionNeural Mechanisms underlying Human Proprioception
Lay Description (from application):
This is a study of the senses which arise from our muscles and which tell us where our different body parts are,
at any point in time. These senses, collectively called proprioception, are also involved in the automatic,
unconscious control of our muscles. So, ultimately, they allow us to stand and to move freely with precision
and confidence, even in the dark. One of these senses, the sense of effort or of heaviness, is believed to be
generated within the brain. It intensifies when we become fatigued. These experiments will be concerned with
finding out more about how this works. We have a method that uses magnetic stimulation of the brain to
change its control of our muscles. Using it we will learn how this sense is generated. When we close our eyes
and move our limbs we realise that we know exactly where they are at any point in time. It remains uncertain
exactly how this information is generated within the nervous system. One idea, arising from some recent
experiments which we want to test, is that as we move the limb, the skin over the moving parts is stretched and
stretch-sensitive nerve endings in the skin provide us with information about the movement. Alternatively,
perhaps it is the effort we exert to maintain limb position against the force of gravity which tells us where the
limb is. In another recent study we have found that when a muscle has become painful from excessive exercise
or from some local strain injury, our ability to control the muscle and so move the limb is no longer as
effective. We want to study the underlying nervous mechanisms responsible for the changes in movement
control. Are they designed to spare the muscle while it recovers from injury? How are they brought about? All
of this work is important for a better understanding of ourselves, for a better clinical diagnosis when something
goes wrong and for improved treatment of diseased or injured muscles.
Research achievements (from final report):
Adequate proprioception is critical for the performance of all voluntary movements and postures. This grant
has revealed new aspects of this important but somewhat neglected group of sensations. A key study used
paralysis and anaesthesia of the arm and this has provided novel definitive evidence for signals related to motor
commands being used in judgement of human joint position. Evidence was provided that conditioning elbow
muscles could lead to systematic errors in position sense in the vertical plane. Loading arm muscles led to
reduction in conditioning-dependent errors. However, loading the arm did not produce extra errors for position
matching in the horizontal plane, as predicted by the motor command hypothesis. Our new view is that a
forward 'internal model' operates which compares observed and anticipated feedback signals., In addition,
cutaneous stretch receptors were shown to contribute for the first time to movement sense at the elbow and
knee. But, Pacinian receptors selectively impaired movement detection. Further work showed that pain inputs
impaired the detection of movement. These three findings reveal new avenues for study. ,
Expected future outcomes:
Further publications will evolve from research conducted during the grant. These will focus on novel
impairments of proprioception produced by muscle pain and muscle damage in humans.
Name of contact:
Professor Simon Gandevia
Email/Phone no. of contact:
s.gandevia@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 350840
Start Year: 2005
CIA Name: Prof Ann Williamson
End Year: 2009
Admin Inst: University of New South Wales
Grant Type: Established Career Fellowships
Main RFCD: Environmental and Occupational Health and Safety
Total funding: $670,500
Title of research award:
Uncoupled Research FellowshipUncoupled Research Fellowship
Lay Description (from application):
Not Available
Research achievements (from final report):
The overall aim of my research is to improve our understanding of the causes and effects of fatigue on
performance and safety and to develop better ways of overcoming the effects of fatigue especially in transport.
Over the past five years my research has clarified the relative effects of sleep deprivation and time of day on
performance. This research showed that night work can be performed safely and without error if the person is
properly rested whereas long work hours that extend into the midnight to dawn, circadian trough period should
be avoided as this combination of factors has clear adverse effects on performance. My research on fatigue and
the road transport industry showed that short haul light trucking produced as much fatigue for drivers as long
haul heavy trucking even though the causes were very different. Short haul drivers do shorter, daytime shifts,
but work under very high pressure, but long haul drivers do extremely long hours and work at any time across
the 24 hour clock. My research on long haul trucking also showed that drivers who are paid on a productivitybased payment system were twice as likely to experience fatigue and three times more likely to resort to
stimulant drugs as drivers paid a salary or by the hour.
Expected future outcomes:
This research has clear policy impact and I am working with regulators and industry in the transport industry
on changing work practices with respect to fatigue risk management.
Name of contact:
Ann Williamson
Email/Phone no. of contact:
a.williamson@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 350852
CIA Name: A/Pr Janet Taylor
Admin Inst: University of New South Wales
Main RFCD: Motor Control
Total funding: $311,250
Start Year: 2005
End Year: 2007
Grant Type: NHMRC Project Grants
Title of research award:
How Changes in the Motor Cortex and Spinal Cord with Exercise Contribute to Fatigue in HumansHow
Changes in the Motor Cortex and Spinal Cord with Exercise Contribute to Fatigue in Humans
Lay Description (from application):
Fatigue with exercise is a common experience in healthy people and can be a problem in many illnesses. With
fatigue people are less able to produce force with their muscles. Much of this weakness occurs because of
events in the muscles but some results from changes in the nervous system. The size of the contribution of the
nervous system to fatigue is not known for the kinds of exercise that cause fatigue in everyday life e.g.
prolonged weak contractions like holding the shopping or a plate of food, rhythmic contractions like walking or
painting a wall, and more vigorous exercise that causes changes in breathing and body temperature. The
behaviour of nerve cells in the brain and spinal cord is altered in fatigue but how and why many of these
changes occur, and how they affect the control of movements, is poorly understood. Three approaches are
planned. In the first set of studies, we will use brain and nerve stimulation to measure the impact of sustained
low-level activities on people's ability to drive their muscles fully. We will identify whether such activities, as
well as increased demands on other body systems, can cause fatigue in the nervous system. In the second set of
studies, we will investigate whether changes in the motor areas of the brain can alter peoples' performance of
fatiguing motor tasks or their perception of how much effort the tasks take. Finally, we will use stimulation of
the spinal cord to work out why motor nerve cells in the spinal cord fire more slowly with fatigue.Fatigue is an
important symptom which is not confined to diseases of any one system in the body. For example, it is a major
complaint in multiple sclerosis, cardiac failure, chronic obstructive airway disease, depression and cancer, as
well as after chemotherapy, surgery, and viral illness. The implications of better understanding of the
contribution of the nervous system to fatigue range from targeting treatments in patients to improving the
performance of athletes.
Research achievements (from final report):
Fatigue with exercise is common in healthy people and is magnified in many illnesses. Some of the loss of
force in muscle fatigue is due to changes in the nervous system. We have demonstrated for the first time that
processes in the nervous system are important during the development of fatigue in submaximal contractions.
In particular, in weak sustained efforts, supraspinal fatigue can account for a half to two-thirds of the force loss.
Supraspinal fatigue develops during rhythmic arm movements as well as in static contractions and so is likely
to be a factor in all kinds of exercise. Investigation of the influence of some of the systemic effects of exercise
showed that supraspinal fatigue is exacerbated by hyperthermia with some of this due to changed muscle
properties. However, high rates of breathing had no effect on performance of fatiguing arm contractions. , In
conjunction with these studies on fatigue in the nervous system, we also developed a new technique for
measuring changes in muscle behaviour during voluntary contractions.
Expected future outcomes:
Our methods allow simultaneous measurement of supraspinal fatigue, cortical behaviour and muscle fatigue to
be measured simultaneously. We expect these methods to be useful in investigating the contributors fatigue in
different patient groups.
Name of contact:
Janet Taylor
Email/Phone no. of contact:
j.taylor@powmri.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 350855
Start Year: 2005
CIA Name: Prof Stephen Lord
End Year: 2007
Admin Inst: University of New South Wales
Grant Type: NHMRC Project Grants
Main RFCD: Optometry not elsewhere classified
Total funding: $493,000
Title of research award:
A randomised controlled falls prevention trial of long distance glasses in elderly multifocal wearersA
randomised controlled falls prevention trial of long distance glasses in elderly multifocal wearers
Lay Description (from application):
Each year, one-third to a half of people over 65 years old will fall at least once. The consequences of falls are
immense in terms of suffering, loss of independence, fear of future falls, carer burden, mortality, residential
care admissions and other health care resource usage. Clearly, effective and affordable falls prevention
strategies are needed to address this major health care problem. Over 50% of people over 65 years old use bi, tri- or multi-focal glasses. The lower part of these glasses are useful for reading and seeing at close range only
and there is now evidence that the use of these glasses is associated with an increased risk of falls due to the
blurring of vision when looking through the lower lenses at ground level obstacles. This is particularly relevant
in unfamiliar outdoor situations. This study will determine whether providing plain distance glasses (with
extensive counselling and recommendations for use in standing and walking activities) will prevent falls and
their consequences over a one year period in older persons who wear bi-, tri- or multi-focal glasses. Pilot
studies suggest that most elderly bi-, tri-, or multi-focal wearers at risk for falls are willing to purchase and use
a second pair of glasses if the benefit of new plain distance glasses for their vision is demonstrated. We expect
that the results of the study will be incorporated into all relevant areas of clinical practice and public health
strategies.
Research achievements (from final report):
There are over 2.4million people aged over 65years of age in Australia, one third of whom fall annually at least
once. As age advances, visual condition called presbyopia in which the crystalline lens of the eye losses its
flexibility makes focusing on close objects difficult. To correct this people are prescribed separate single lens
glasses for distant and near vision or for convenience bi/tri/progressive lens glasses for conducting daily tasks
for e.g. driving, shopping and cooking. Consequences of falls are immense in terms of suffering, loss of
independence, suffering, fear of future falls, carer burden, mortality, residential care admission and other health
care resource usage. Previous research shows that most falls occur outside due to "trips". Our trial attempts to
minimize the potential harm associated with the use of multifocal glasses.
Expected future outcomes:
Reduction in falls rate and related morbidity, resulting in reduced demand for acute, subacute and non-acute
health services, with low-cost, accessible intervention.
Name of contact:
Professor Stephen Lord
Email/Phone no. of contact:
s.lord@powmri.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 350860
CIA Name: A/Pr Tony Butler
Admin Inst: University of New South Wales
Main RFCD: Epidemiology
Total funding: $591,000
Start Year: 2005
End Year: 2007
Grant Type: NHMRC Project Grants
Title of research award:
A survey of the sexual behaviour and sexual health of Australian prisonersA survey of the sexual behaviour
and sexual health of Australian prisoners
Lay Description (from application):
The Australian Study of Health and Relationships telephone survey recently reported on the sexual attitudes,
knowledge, health and behaviour of over 19,000 Australians. One of the groups that was omitted from that
survey was prisoners. Yet prisoners are a high-risk group for sexual ill health. Prisoners are mostly drawn from
the most disadvantaged groups in society: they are more likely to be unemployed, they have less education and
lower incomes than other Australians, and many suffer from minor intellectual disabilities and/or mental
illness. This proposed survey of inmates in Australian prisons will fill in this missing data. Prisoners are the
forgotten population in many countries. Only a few surveys of prisoners' health have been performed. There are
some surveys of sexual behaviour in particular prisons overseas, though most of them concentrate on HIV risks
and do not explore the sexual lives of prisoners in the same way as the major national sex surveys in the US,
the UK and France did for people living outside prison. Prison is itself a dangerous place for people's sexual
health. In prison, much of the sex that occurs is not voluntary. Sexual assault in prisons can lead to serious
physical injury as well as risk of sexually transmitted diseases including HIV/AIDS. Although some of these
injuries can be sufficiently serious to require surgery, only a small proportion are reported to the authorities.
Younger prisoners (aged 18-25) and those who are small, slightly built or gay, are at higher risk of being
assaulted. This study will explore the factors surrounding sexual assault in prison and make recommendations
for preventing it.
Research achievements (from final report):
- The study has been able to describe in detail for the first time the sexual health and behaviours of Australian
prisoners. , , - It has helped to debunk the myth of high rates of prisoner rape in Australian correctional
facilities., , - The study has also contributed to the public health debate on condom and dental dam provision in
prisons. We found that condom/dental dam provision does not promote increased sexual activity (consensual
and non-consensual) in prison.
Expected future outcomes:
- Possible development of interventions on sexual safety for prisoners. , - Input into evidence-based decisionmaking for prisoner welfare and services.,
Name of contact:
Tony Butler
Email/Phone no. of contact:
t.butler@curtin.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 350889
CIA Name: Prof Vaughan Macefield
Admin Inst: University of New South Wales
Main RFCD: Sensory Systems
Total funding: $375,750
Start Year: 2005
End Year: 2007
Grant Type: NHMRC Project Grants
Title of research award:
THE AUTONOMIC, SOMATIC AND CENTRAL NEURAL RESPONSES TO DEEP AND SUPERFICIAL
PAIN IN HUMAN SUBJECTSTHE AUTONOMIC, SOMATIC AND CENTRAL NEURAL RESPONSES
TO DEEP AND SUPERFICIAL PAIN IN HUMAN SUBJECTS
Lay Description (from application):
Pain is a subjective experience, the intensity of which can be readily influenced by personal experience.
Despite this, pain originating from a particular part of the body will usually be described by all individuals as
having similar character. For example, pain arising from the skin is commonly described as being sharp or
burning and is usually easy to localise, whereas pain arising from muscle is commonly dull, throbbing and
diffuse. In addition to producing sensory changes, pain also evokes changes in blood pressure, heart rate and
motor activity (often in an attempt to remove the source of the pain). The proposed research aims to
characterise the cardiovascular and motor patterns associated with pain originating in skin and in muscle and to
examine the brain regions that produce these changes. More specifically, microelectrodes will be used to
investigate changes in peripheral nerve activity during transient painful skin and muscle events in awake
human subjects. In a separate investigation functional magnetic resonance imaging will be used to determine
brain sites that are activated by skin or muscle pain.
Research achievements (from final report):
This research has made significant contributions to knowledge on the effects of autonomic, somatic and central
responses to pain. We have used brain imaging to revela the differences in processing of pain originating in
muscle and skin, and uncovered a hitherto unknown gender difference in pain processing. Moreover, we have
documented for the first time differences in how the sympathetic nervous system, important in the regulation of
blood pressure and blood flow, responds to acute pain. Finally, our work has provided detailed evidence that
refutes the 'vicious-cycle' theory of muscle pain - an hypothesis based on animal experiments and which
underpins many pain management strategies.
Expected future outcomes:
While this project examined the effects of acute pain, induced by bolus injections of hyeprtonic saline into
muscle or skin of awake human subjects, in 2009 we shall be submitting a Project Grant that extends this work
by examining the effects of tonic muscle pain, induced by intramuscular infusion of hypertonic saline. This
more closely approximates the onging pain associated with chronic pain.
Name of contact:
Prof Vaughan Macefield
Email/Phone no. of contact:
v.macefield@uws.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 350903
CIA Name: A/Pr James Brock
Admin Inst: University of New South Wales
Main RFCD: Peripheral Nervous System
Total funding: $408,000
Start Year: 2005
End Year: 2007
Grant Type: NHMRC Project Grants
Title of research award:
Mechanisms underlying disordered skin blood flow following nerve injuryMechanisms underlying disordered
skin blood flow following nerve injury
Lay Description (from application):
Many people who recover from traumatic injury or who have chronic conditions such as diabetes or neuropathy
from exposure to a toxic chemical suffer from peripheral vascular disorders leading to poor circulation in the
extremities. These conditions are characterised by impaired wound healing, cold hands and feet and ongoing
pain. These people must face a long life with progressively increasing disability. Even normal ageing can lead
to similar problems. This project is directed at understanding the role of the nerve supply to blood vessels in
the skin in these disorders. The experiments will be conducted in skin blood vessels of rats with various forms
of nerve lesion that will mimic these conditions in patients. We will use our knowledge of the structure and
behaviour of nerve/blood vessel connections to analyse the changes in the properties of vascular smooth
muscle and relate it to the state of the innervation. Skin arteries normally receive two types of nerve sympathetic (which release noradrenaline) and afferent ( which release peptides) - that have opposing actions
on the vessel (constriction and dilation respectively). We hypothesize that removal of part or all of the
innervation changes the contractile mechanism of the smooth muscle in the wall of the vessel so that it
becomes much more sensitive to calcium ions and produces larger and more prolonged contractions. We will
combine electrophysiology and contraction studies with immunohistochemistry and biochemical analysis to
define the relation between the nerve deficit and the vascular responses. The aim is to identify appropriate
drug targets for which local application in the affected region can alleviate the symptoms without causing
widespread side effects.
Research achievements (from final report):
Nerve injuries and neuropathies that cause loss of vascular innervation produce disordered regulation of skin
blood flow and are associated with altered skin function, including sensory disturbances and persistent skin
ulcers that are difficult to treat. In this project we have characterised the effects of surgically induced injuries to
the nerves that supply of blood vessels in skin. The findings demonstrate adaptions of nerves, rather than
changes in behavour of muscle within the artery wall, maintain neural control of blood vessels. This is
surprising because clinical assessments have used changes in responsiveness of the artery muscle to indicate
denervation in dieases such as diabetes. Deficits in the neural control of arteries only occur when greater than
50 % on the nerves are lost. The findings should change the clinical assessment of sympathetic nerve damage is
diseases such as diabetes.
Expected future outcomes:
The completed experimental work provides the groundwork for future studies investigating the changes that
underlie diabetes- and inflammation-induced changes in neural control of skin blood flow
Name of contact:
James Brock
Email/Phone no. of contact:
j.brock@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 351000
Start Year: 2005
CIA Name: Dr Shauna Sherker
End Year: 2009
Admin Inst: University of New South Wales
Grant Type: Early Career Fellowships (Australia)
Main RFCD: Public Health and Health Services not elsewhere classified
Total funding: $290,298
Title of research award:
A program of evidence-based sports injury prevention injuries.A program of evidence-based sports injury
prevention injuries.
Lay Description (from application):
Not Available
Research achievements (from final report):
There were many achievements in the research program of evidence-based sports injury prevention initiatives.
Research projects undertaken included: , - A review of NSW sports injury hospitalisation and deaths, Establishing a framework for review of motorsports injury in NSW, - Identifying risk and protective factors for
mild traumatic brain injury, - The role of alcohol, drugs and fatigue towards injury risk attitudes and
perceptions among high-risk sports participants, - Evaluating risk management training to improve the safety
activities of community sport, - Review of guidelines for prevention of heat illness in sport , - Encouraging
compliance with safety standards in local government playgrounds, - Evaluation of a national campaign to
reduce the risk of beach drowning
Expected future outcomes:
It is anticipated that this research will contribute to future evidence-based sports injury prevention initiatives.
Name of contact:
Shauna Sherker
Email/Phone no. of contact:
shaunasherker@gmail.com
NHMRC Research Achievements - SUMMARY
Grant ID: 400918
Start Year: 2006
CIA Name: Prof Elspeth McLachlan
End Year: 2008
Admin Inst: University of New South Wales
Grant Type: NHMRC Project Grants
Main RFCD: Neurosciences not elsewhere classified
Total funding: $457,268
Title of research award:
Delayed neuronal death after peripheral nerve and spinal cord injuryDelayed neuronal death after peripheral
nerve and spinal cord injury
Lay Description (from application):
After injury to the nervous system, even under optimal conditions for regeneration of broken nerve processes
(axons), there is little chance of normal function being restored because few regrowing axons will find
appropriate cells to connect with. The time taken for many regrowing axons to reach their targets can be so
long that both the axons and their targets lose the ability to recognize each other. Equally importantly, some
damaged nerve cells die over the months that follow an injury. This slow loss of nerve cells can lead to
progressive and ongoing deterioration. Given recent advances in our understanding of how to improve axon
regeneration, the degree of functional recovery could be disappointing unless we know more about how to
prevent these neurones from dying. This project will use rats as experimental animals to try to understand
which types of nerve cells are likely to die or survive after injury to peripheral nerve trunks or to the spinal
cord. We will investigate two regions of the nervous system that are commonly involved in injuries in people.
After injuries to limb nerves, people lose sensation and movement and can unpredictably develop chronic
conditions such as neuropathic pain (unrelated to the damage and often occurring spontaneously) as well as
poor blood flow and wound healing in the hands/feet. After most injuries to the spinal cord, the lower part of
the cord beyond the injury (in particular the lumbosacral cord controlling hindlimb movement and sensation
and the function of bladder, bowel and sexual organs) is often disconnected from the brain leading to paralysis
and disrupted control of pelvic organ function. We will identify and study specific populations of nerve cells
with sensory (mainly pain-sensing) functions and four identified groups of nerve cells in the lumbosacral cord
that project to the brain. Once we know which nerve cells do not survive, we will search for the likely causes
of their death and ways to prevent it.
Research achievements (from final report):
We have identified in experimental animals that at least half of the nerve cells in the spinal cord below a spinal
cord injury that normally project to the brain and upper parts of the spinal cord die within 2 months after their
long ascending processes are broken. Our analysis suggests that particular pathways are more vulnerable than
others. We have some evidence suggesting that the late influx of T-lymphocytes into the cord may be involved
in this type of cell death. , Studies on animals with peripheral nerve injuries have indicated that the small
sensory nerve cells that innervate the skin are particularly vulnerable and die over the months that follow the
lesion. These nerve cells are responsible for sensing painful stimuli. To try to identify the factors responsible
for the death of the injured nerve cells, we have labelled them at the time of injury and have followed their
survival over time. By analysing the effects of a series of distinct types of lesion, we plan to find out whether or
not the invasion of immune cells around the cell bodies of these cells is protective or destructive. We have
found increasing numbers of T-lymphocytes around the sensory nerve cells over the period of their death. We
hope to determine the nature of this relationship between the immune system and damaged nerve pathways.
Expected future outcomes:
If these findings apply in humans, they imply that the outcome of regenerative strategies after spinal cord
injury may not be successful if the time to reach the lower parts of the cord is prolonged. The loss of sensory
nerve cells that normally detect damaging stimuli may underlie neuropathic pain. Ways to protect against
degeneration of specific groups of nerve cells will need to be developed.
Name of contact:
Elspeth McLachlan
NHMRC Research Achievements - SUMMARY
Email/Phone no. of contact:
e.mclachlan@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 400941
CIA Name: Prof Stephen Lord
Admin Inst: University of New South Wales
Main RFCD: Geriatrics and Gerontology
Total funding: $355,878
Start Year: 2006
End Year: 2008
Grant Type: NHMRC Project Grants
Title of research award:
Understanding fear of falling and risk taking in older peopleUnderstanding fear of falling and risk taking in
older people
Lay Description (from application):
Fear of falling is a very significant issue for many older people. Estimates of the prevalence of fear of falling in
older community-dwelling people range from 29 to 92% in those who have suffered previous falls, and 12 to
65% in those have not. Fear of falling can lead to restriction and curtailment of activity, reduced quality of life,
anxiety, depression and social isolation. To date, all studies addressing fear of falling have simply considered
no fear to be "good" and presence of fear to be "bad", and have not attempted to assess whether this fear is
rational or irrational in relation to actual balance abilities or physical functioning. In this study, we aim to find
out which psychological, physical, health and lifestyle factors distinguish between older people with and
without an irrational fear of falling based on their actual physical falling risk. We also wish to understand the
role that fear of falling and other psychological factors (anxiety, depression and avoidance) play in causing
older people to fall; and to measure how falls can lead to increased fear of falling, anxiety and depression and
reduced physical functioning. The complex nature of psychological risk factors of falling and the limited
background information on this subject, hampers its integration in falls prevention programs. Although there is
growing awareness of this problem among health care providers, additional research is needed about why older
people develop a fear of falling in order to fully understand fear of falling and to tailor specific intervention
and prevention strategies.
Research achievements (from final report):
To date, all studies addressing falls efficacy have simply considered high falls efficacy to be "good" and low
falls efficacy to be "bad", and none have attempted to categorise people in relation to their actual balance
abilities or physical functioning. This is vital as it has important implications for understanding falls efficacy
and developing appropriate intervention strategies. , In this study 500 community-dwelling older people (age:
70+) were assessed. At baseline, participants completed assessments of fear of falling, physical functioning,
activity levels, depression, anxiety, health status, risk-taking behaviours and neuropsychological performance.
Participants were followed up monthly for falls and three-monthly for fear of falling over a one-year period,
with a final physical reassessment at 12 months. , For statistical purposes participants were categorised in
relation to how well their perceived fall risk (i.e. fear of falling) matched their actual fall risk (based on
physical tests). This resulted in four groups: adaptive, phobic, risk-taking and vigorous. , The findings indicate
that an excessive concern about falling increases the risk of falls. This elevated concern appears to be related to
anxiety, depression and reduced neuropsychological functioning. On the other hand, an underestimation of
concern does not appear to increase the risk of falls. Having a low concern of falling and a positive outlook on
life, irrespective of physical fall risk, appears not to lead to excessive risk taking and may promote an active
and healthy lifestyle.
Expected future outcomes:
We hope to develop an explanatory model of the association between fear and falls, in order to provide a solid
foundation from which treatment providers can put in place, safe, appropriate and effective interventions.
Name of contact:
Stephen R Lord
Email/Phone no. of contact:
S.Lord@powmri.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 400947
CIA Name: Prof David Tracey
Admin Inst: University of New South Wales
Main RFCD: Sensory Systems
Total funding: $262,959
Start Year: 2006
End Year: 2008
Grant Type: NHMRC Project Grants
Title of research award:
Does the complement system contribute to neuropathic pain?Does the complement system contribute to
neuropathic pain?
Lay Description (from application):
Nerve injury often results in increased sensitivity to painful stimuli and the perception of innocuous stimuli as
painful; it may also result in spontaneous pain. These disorders of pain sensation due to nerve injury are
common, debilitating and difficult to treat. They are symptoms of neuropathic pain. Pain is normally signalled
to the brain by sensory nerve cells called nociceptors. Following nerve injury, nociceptors are sensitised by
chemicals released by inflammatory cells. This contributes to neuropathic pain. We have evidence that
inflammatory responses play a key role in initiating neuropathic pain. Other evidence suggests that the
immune system contributes to neurological diseases and accompanying pain (e.g. Guillain-Barr syndrome and
multiple sclerosis). We plan to test the idea that a component of the immune system known as the complement
pathway contributes to the development of neuropathic pain following peripheral nerve injury. The outcome
of this work will be a better understanding of the way in which nerve injury leads to chronic disorders of pain,
including increased sensitivity to painful stimuli. This will lead in turn to the development of more effective
treatments for neuropathic pain.
Research achievements (from final report):
Neuropathic pain is a persistent pain often caused by nerve injury. Such pain is a debilitating condition that
lacks effective treatment and represents a significant health problem because it interferes with daily activities
leading to reduction in quality of life, reduced productivity and significant health care costs. Recently it has
become clear that interactions between the nervous system and the immune system play an important role in
neuropathic pain. In this project, we demonstrated that peripheral nerve injury induces C3 deposition and
activates the complement system. This contributes in turn to leukocyte recruitment and neuropathic pain.
Complement inhibition markedly suppresses C3 deposition and lymphocyte and macrophage recruitment to the
injured nerve and produces significant alleviation of neuropathic pain. This research benefits the scientific
community and the general population. This study significantly enhances our understanding of the immune
mechanisms underlying neuropathic pain and offers a new approach to therapeutic intervention by means of
complement inhibition. Findings have already been reported in international peer-reviewed journals and at
professional meetings in Australia and overseas, and are expected to attract considerable international attention
and thereby raise the profile of Australian science in the field of neuroscience.
Expected future outcomes:
Complement inhibitors including soluble complement receptor 1 (sCR1) have shown efficacy in controlling the
pathologic consequences of several disorders (e.g. reperfusion injury, rheumatoid arthritis, multiple sclerosis,
Alzheimer's disease and stroke) and our data support complement inhibition as a potential therapeutic approach
for neuropathic pain.
Name of contact:
Gila Moalem-Taylor
Email/Phone no. of contact:
gila@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 401102
CIA Name: Prof George Paxinos
Admin Inst: University of New South Wales
Main RFCD: Central Nervous System
Total funding: $441,750
Start Year: 2006
End Year: 2008
Grant Type: Established Career Fellowships
Title of research award:
Uncoupled Research FellowshipUncoupled Research Fellowship
Lay Description (from application):
Not Available
Research achievements (from final report):
Studies of the brain have the allure of discovering the cause and treatment of disorders such as schizophrenia,
depression and Alzheimer's disease. The aim of the fellowship was to provide the basic maps of the normal
human brain and spinal chord, and to establish the homologies, correspondencies, between the brains of
humans and experimental animals. , , The Atlas of the Human Brain, 3rd Edition, was published in 2008 (Mai,
Paxinos and Voss). This work is the most accurate atlas of the human brain available and is now used by
stereotaxic neurosurgeons when they want to accurately target small structures deep in the brain. The atlas is
also used to interpret the images in the clinic, and to identify areas activated in functional MRI experimental
studies. , , Under the present fellowship, I completed work started earlier: on the atlas of the avian brain (The
Chick Brain in Stereotaxic Coordinates) and the atlas of the developing mouse brain (Atlas of the Developing
Mouse Brain). In the Chick Brain Atlas we identified 180 areas that were either unknown to science or were
not known to be present in the bird (but were known to be present in mammals). I also did most of the work on
our spinal cord atlas., , The above atlases permit scientists to navigate seamlessly between the brains of humans
and experimental animals, to test hypotheses inspired by human considerations. I also published studies on the
human hypothalamus and autonomic control areas, as well as the echidna brain.
Expected future outcomes:
The maps that have been constructed in my laboratory are used internationally to map the brain and its
functions. Most scientists studying the relationship between brain and disease either in humans or experimental
animal models use these maps.
Name of contact:
George Paxinos
Email/Phone no. of contact:
g.paxinos@neura.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 401105
CIA Name: Prof Vaughan Macefield
Admin Inst: University of New South Wales
Main RFCD: Autonomic Nervous System
Total funding: $295,313
Start Year: 2006
End Year: 2008
Grant Type: Established Career Fellowships
Title of research award:
Uncoupled Research FellowshipUncoupled Research Fellowship
Lay Description (from application):
Not Available
Research achievements (from final report):
I have established world-class laboratories at the Prince of Wales Medical Research Institute and at the
University of Western Sydney where I undertake detailed human neurophysiological studies that are unique in
Australia. The research work involves recording from (or stimulating) individual nerve fibres via tungsten
microelectrodes inserted percutaneously into the peripheral nerves of human subjects (microneurography). I
work collaboratively with colleagues at a national and international level and my research is applied to
clinically relevant problems by establishing collaborations with clinical specialists. In addition to research
examining the changes in control of the autonomic nervous system following human spinal cord injury, my
research over the last 8 years has extended to clinical studies of various cardiovascular and respiratory disease
states: congestive heart failure, obstructive sleep apnoea syndrome, chronic obstructive pulmonary disease and
essential hypertension., During the tenure of my Fellowship I have hosted five sabbatical visitors to my
laboratory - three from overseas and two from Australian universities - and hosted six postdoctoral scientists
who have come with their own funding. My research group has grown from two in 1995 to eight by 2005. I
currently have four postdocs working with me and am also supervising one Honours and three PhD students., I
have written 65 papers and reviews that have been published in the leading international journals in their fields
(e.g. 15 papers in the Journal of Physiology), of which 36 have been published during the tenure of my
Fellowship.
Expected future outcomes:
Impacting positively on our quality of life as we age, research into the role of the sympathetic nervous system
and cardiovascular control using microneurography techniques and brain imaging (fMRI) will increase our
understanding of how normal blood pressure is maintained and how different disease states influence this
control.
Name of contact:
Prof Vaughan G Macefield
Email/Phone no. of contact:
v.macefield@uws.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 401189
CIA Name: Prof Nigel Lovell
Admin Inst: University of New South Wales
Main RFCD: Instruments and Techniques
Total funding: $199,105
Start Year: 2006
End Year: 2006
Grant Type: NHMRC Development Grants
Title of research award:
Development of a wearable triaxial accelerometer with embedded algorithms to detect and prevent falls in frail
older aduDevelopment of a wearable triaxial accelerometer with embedded algorithms to detect and prevent
falls in frail older adu
Lay Description (from application):
Not Available
Research achievements (from final report):
We developed a wireless ambulatory monitor called a 'PreventaFall' to assist in the detection, management and
assessment of falls risk in the elderly. The falls monitoring system is based on a sensor known as a triaxial
accelerometer. It can also be used to assess activity level and postural orientation. The device has an in-built
algorithm that can be used to automatically detect a fall or stumble and create a voice connection with a call
monitoring centre - thus performing the task of an advanced personal alarm system. Currently there are more
than 30,000 pendant alarm systems in use in Australia and approximately eight times this number in the UK.
Such systems are simple passive devices which need to be activated by the user for an alarm to be registered.
They can play no role either in preventing falls or in assessing the likely risk of an imminent fall, or to generate
an alarm automatically should a fall occur and the user is unconscious. In contrast, this PreventaFall device has
these capabilities.
Expected future outcomes:
We are currently working to allow the PreventaFall to prompt the wearer to perform a routine set of
movements. From these movements we hope to derive indicators of stability and ambulation and thus have a
device that can be used to assess and manage falls risk, with the end aim of creating a system that effectively
prevents falls.
Name of contact:
Prof Nigel Lovell
Email/Phone no. of contact:
N.Lovell@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 455215
CIA Name: Prof Simon Gandevia
Admin Inst: University of New South Wales
Main RFCD: Central Nervous System
Total funding: $365,105
Start Year: 2007
End Year: 2009
Grant Type: NHMRC Project Grants
Title of research award:
Novel assessments of the central and peripheral control of the human handNovel assessments of the central and
peripheral control of the human hand
Lay Description (from application):
This is a study of how the human hand works. The hand is supremely adapted for manual skills ranging from
writing and playing a musical instrument to non-verbal communications via gesture and pointing. How is the
range of hand skills achieved? We are motivated to study this because the ability of the hand to recovery from
some neurological disorders, particularly stroke, is very poor. One important element in virtually all activities
of the hand is precise movement of the thumb. The tip of the thumb is flexed by a single muscle, a muscle only
present in humans. We want to determine how this muscle works, and how the force it produces affects the
whole hand. We will use specialised neurophysiological techniques to do this in human volunteers. There is
no comparable animal model for this type of work due to significant differences at both the level of the brain
and the level of the muscle. Second, we want to understand better how the cells in the spinal cord which
control the hand (and other) muscles work. We have two new ways to do this, including a novel technique
which can activate these cells with a form of stimulation that may help us improve functional electrical
stimulation. Finally, with 27 bones and more than 25 muscles which operate it, the hand is not simple to
control. We will use a new apparatus to measure how well it is controlled, and we will directly stimulate the
motor areas of the brain to evaluate the control. From this, we will come up with new understanding, as well as
new stimulus and measurement techniques that can be applied to patients with impaired hand function, as
occurs all too often after stroke.
Research achievements (from final report):
This project aimed to reveal key principles involved in the central and peripheral control of the human hand at
the level of the muscles, the spinal motoneurone pools, and the motor cortex. W tried to find out (1) why the
control of the human thumb is special, (ii) how the various hand muscles are coordinated to produce strong
hand forces, and (iii) how the brain controls the muscles which extend the fingers to lift them from grasped
objects. We developed a new method for testing voluntary drive to the hand and examined novel ways that
muscle can produce force when stimulated electrically. This work will contribute to understanding hand
function and how it can be affected by disease.
Expected future outcomes:
N/A
Name of contact:
Professor Simon Gandevia
Email/Phone no. of contact:
s.gandevia@neura.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 455316
CIA Name: A/Pr Janet Taylor
Admin Inst: University of New South Wales
Main RFCD: Central Nervous System
Total funding: $393,201
Start Year: 2007
End Year: 2009
Grant Type: NHMRC Project Grants
Title of research award:
Corticospinal transmission in human subjectsCorticospinal transmission in human subjects
Lay Description (from application):
The corticospinal pathway is the major route from the brain to the spinal cord for the control of voluntary
movement in people. Little is known about how transmission through this pathway might alter with activity. It
is known that, elsewhere in the brain, connections between nerve cells can be made stronger or weaker by
specific patterns of activity and it is thought that such changes underlie learning and memory. We propose that
similar changes might happen in the spinal cord at the connection between the nerve cells which carry signals
from the brain and the nerve cells which carry the signals out to the muscle. This project will demonstrate that
the connections in the pathway from the brain to the muscle can be strengthened or weakened in a controlled
way by imposed patterns of activity. In addition, we know that after voluntary contractions, there are dramatic
changes in the way signals in this pathway are transmitted to muscles. After brief strong voluntary
contractions, muscle responses are immediately reduced. After longer contractions in which the muscles
become fatigued, the reduction is followed by an increase in responses which can last many minutes. Thus, this
project will also study changes in the pathway from the brain to the muscle after natural activity. The effects of
changes induced by artificial or natural activity on the control of voluntary movement will also be investigated.
Understanding how activity drives changes in the pathway that controls voluntary movement is important for
all situations that involve learning motor tasks. These include normal development and learning of motor
skills, as well as rehabilitation after all kinds of nerve or muscle injury. It is also important in understanding
motor changes that occur when activity is altered by disorders like spinal cord injury or stroke. Improved
understanding of the processes occuring should allow improvement in rehabilitation therapies.
Research achievements (from final report):
To deliberately move our limbs and bodies we send signals from the brain to activate nerve cells in the spinal
cord. In turn, these nerve cells signal the muscles. Our research concentrated on the connection between the
corticospinal tract, the main pathway which conveys movement signals from the brain, and the nerve cells that
convey the signal to the muscle. Our studies found that this connection is not a simple relay but can be changed
both by a person's voluntary activity and by artificial stimulation. The findings related to voluntary activity
suggest that changes at a spinal cord level influence our control of our muscles in the short-term, and in the
longer-term, the connections in the pathway from the brain to the muscles may adapt their strength and
behaviour to the way we use each of our muscles. We also developed a method which uses nerve stimulation in
a precisely timed way to modulate the strength of the connections. This demonstration of plasticity in the spinal
cord in the path that controls movement may lead to a rehabilitation technique to help strengthen connections
between the brain and the muscle when these have been reduced by injury.
Expected future outcomes:
Our work will help understand the role of the spinal cord in learning motor tasks. Further research will
determine whether our method to increase the strength of synaptic connections in the pathway between the
brain and muscles can help improve strength in patients who have incomplete spinal cord injury.
Name of contact:
Dr Janet Taylor
Email/Phone no. of contact:
j.taylor@neura.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 455368
CIA Name: Prof Stephen Lord
Admin Inst: University of New South Wales
Main RFCD: Geriatrics and Gerontology
Total funding: $530,741
Start Year: 2007
End Year: 2010
Grant Type: NHMRC Strategic Awards
Title of research award:
Identification and quantification of risk of falls in cognitively impaired older adultsIdentification and
quantification of risk of falls in cognitively impaired older adults
Lay Description (from application):
This study represents the first systematic approach to understanding the complex interaction of factors that
contribute to risk of falling in cognitively impaired older people. The results will provide much needed
information on how to intervene to prevent falls and fractures in this high risk population. In the last decade, 25
randomised controlled trials have been published which show it is possible to prevent falls in older people.
However, a major disappointing outcome of research in this field is that trials that have included or specifically
focused on older people with cognitive impairment have been unsuccessful in preventing falls. Cognitive
impairment has long been known to be a major risk factor for falls and fractures but little research has been
undertaken to understand the underlying mechanisms as to why this is the case. It is likely that previous falls
prevention trials involving people with cognitive impairment were unsuccessful because they did not directly
assess mechanisms for falls in this group and simply translated intervention strategies from studies undertaken
in cognitively intact older people. This study aims to develop our understanding of the important factors that
contribute to risk of falling in older people with cognitive impairment and dementia. Participants will be
recruited from a number of sources including hospitals, out-patient clinics, retirement villages, hostels etc.
Whilst some participants will be able to consent to take part, all participants must have a nominated "person
responsible". Consenting participants will undergo a series of assessments, the majority of which can be
undertaken in their own home. These will include medical and medication history, measures of gait and
balance and tests assessing performance of different regions of the brain. An MRI scan will allow us to
determine whether risk of falling relates to any specific pathology in different parts of the brain. We anticipate
that we will be able to identify which risk factors and underlying mechanisms are most strongly associated with
falling in cognitively impaired older people. We then hope to use the information to design targeted and
tailored intervention strategies to reduce falls and fractures in this high risk population.
Research achievements (from final report):
This project has systematically assessed falls risk in older people with cognitive impairment. It has provided
clear evidence of marked physiological deficits in this population that are potentially amenable to intervention strength, balance and reaction time. It appears that the physical deficits play a greater role in risk of falls than
any of the neurocognitive measures. However, neurocognitive performance is relevant in terms of potential
interventions for the future.
Expected future outcomes:
The study finished in March 2011 and a pilot study for intervention has also been undertaken and has provided
additional information on how to shape an intervention for the future. The next step is to undertake an
intervention study and funding is currently being sought.
Name of contact:
Jacqueline Close
Email/Phone no. of contact:
j.close@neura.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 455433
CIA Name: Prof Stephen Lord
Admin Inst: University of New South Wales
Main RFCD: Geriatrics and Gerontology
Total funding: $765,883
Start Year: 2007
End Year: 2011
Grant Type: Established Career Fellowships
Title of research award:
Uncoupled Research FellowshipUncoupled Research Fellowship
Lay Description (from application):
I am an applied physiologist determining risk factors for falls and strategies for prevention in older people and
clinical groups with balance disorders. I pursue this research primarily through epidemiological studies.
Research achievements (from final report):
As a Senior Principal Research Fellow I have pursued work in the areas of applied neurology, instability, falls,
fractures and transport injury in older people. In this period (since January 2007) I have published 100 original
peer-reviewed journal articles, 6 invited reviews, 5 other articles and 4 book chapters. With colleagues at
Neuroscience Research Australia (NeuRA) I also completed a second fully revised edition of our book on
Falling in Older People: Risk factors and Strategies for Prevention to be published by Cambridge University
Press. Overall, my papers have been cited over 7,000 times in the scientific literature and my H index is 47.,
Since 2007, I have been awarded $13.7 million grant funding from the NHMRC and $2.0 million from other
sources (total $15.7 million) as a chief investigator. I currently hold two NHMRC project grants, an NHMRC
capacity building grant in population health, 4 grants from other sources as and two recently awarded NHMRC
Partnership Grants which will provide the means of maintaining my research productivity into the future., I
have collaborated directly with health care providers both within Australia and overseas to incorporate
evidence-based risk assessment tools for use in clinical settings to identify high risk populations who might
benefit from interventions. My methodology and approach to the problem of physiological aging measurement
and falls-risk assessment has been adopted by many researchers around the world. Finally, I have played a key
role in developing health policy. I have contributed to policy development for NSW Health and was the Chair
of the Expert Panel for the development of the revised Best Practice Guidelines for Preventing Falls in the
Community, Hospitals and Residential Aged Care Facilities. These very significant developments greatly
enhance the translation of my research findings into policy and practice., ,
Expected future outcomes:
I am continuing to work as an NHMRC Senior Research Fellow. As outlined in my renewal application, I am
embarking on new projects aimed at understanding fall risk in older people and designing and implementing
fall prevention strategies. I continue to work actively in research translation.
Name of contact:
Stephen R Lord
Email/Phone no. of contact:
s.lord@neura.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 510110
CIA Name: Prof Stephen Lord
Admin Inst: University of New South Wales
Main RFCD: Preventive Medicine
Total funding: $564,727
Start Year: 2008
End Year: 2010
Grant Type: NHMRC Project Grants
Title of research award:
Impaired stepping as a risk factor for falls in older peopleImpaired stepping as a risk factor for falls in older
people
Lay Description (from application):
Stepping is often the last protective option to prevent a fall. This study will investigate stepping responses as a
risk factor for falls. Complementary studies of physiological and psychological contributions to stepping will
also be conducted. A path model will be used to examine the relative importance of physiological,
psychological and behvioural factors. An exercise program to imrpove stepping responses will be trialed.
Findings will inform future interventions for preventing falls.
Research achievements (from final report):
This study examined physiological and neurophyschological contributions to appropriate and impaired
responses to postural perturbations and determined the role that impaired stepping plays in predicting future
falls in a large cohort of older adults. We found older adults stepped earlier and with reduced force, compared
to young adults. Force thresholds for stepping were related to balance, strength and reaction time performance
and were predictive of future falls in older adults. Those who responded with multiple steps almost twice as
likely to fall in the future 12 months than those who responded with a single step. A secondary study was
performed to investigate the role of a cognitive dual-task on balance responses. Participants whose stepping
thresholds were reduced in the dual-task condition were over 4 times more likely to have an injurious fall in the
following 12 months than those who were unaffected. These studies have provided insight into how older
adults respond to unexpected balance responses, as well as the relationships with physiological and cognitive
functioning and future falls. Findings will inform future intervention studies to prevent falls in older people.
Expected future outcomes:
Findings highlight important physiological and psychological factors that underpin protective stepping
performance, which will directly inform exercise programs to facilitate appropriate stepping in prevent falls in
older people. Findings also indicate that a simple unexpected backward perturbation assessment may prove
useful in clinical practice to enhance falls risk assessment.
Name of contact:
Professor Stephen Lord
Email/Phone no. of contact:
s.lord@neura.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 510129
CIA Name: A/Pr Jane Butler
Admin Inst: University of New South Wales
Main RFCD: Motor Control
Total funding: $553,403
Start Year: 2008
End Year: 2014
Grant Type: NHMRC Research Fellowships
Title of research award:
Uncoupled Research FellowshipUncoupled Research Fellowship
Lay Description (from application):
I am a neurophysiologist in the field of human motor control. My primary research focus is on the neural
control of respiratory muscles in health and disease including obstructive sleep apnoea and spinal cord injury. I
also study a number of aspects of mu
Research achievements (from final report):
In my laboratory we are interested in the neural control of breathing in health and disease. We study many
aspects of this control in human volunteers. My work over the last 5 years has made significant inroads into the
understanding of the way neural drive to respiratory muscles is linked to their mechanical function. My lab has
also investigated the nature of voluntary control of respiratory muscles which recruits similar populations of
motoneurones as automatic breaything in a similar pattern. I have also extended my work to examine the neural
control of the upper airway in particular with th eaim to improve treatments for people with obstructive sleep
apnoea. In addition I have developed a novel method of electrical stimulation to evoke a functional cough in
people with cervical spinal cord injuries that I believe will reduce the high mortality and morbidity in this
group of people that results from respiratory complications such as pneumonia.
Expected future outcomes:
Potential future outcomes include i the extension of the newly described principl eof neuromechanical
matching ii further investigatio nof the interaction between voluntary and involuntary control of breathing and
iii the development of a commercially available electrical stimulkator that will evoke a functional cough.
Name of contact:
Jane Butler
Email/Phone no. of contact:
j.butler@neura.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 510201
CIA Name: Prof James Colebatch
Admin Inst: University of New South Wales
Main RFCD: Central Nervous System
Total funding: $225,357
Start Year: 2008
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
Vestibular reflexes evoked by brief lateral head acclerations: a new measure of utricular functionVestibular
reflexes evoked by brief lateral head acclerations: a new measure of utricular function
Lay Description (from application):
The vestibular (balance) organs are difficult to investigate as they lie deep within bone. Disease of these
organs may cause severe vertigo, imbalance and difficulty with vision. This project attempts to build on earlier
developments in my laboratory and thereby improve understanding and diagnosis of these disorders. This
grant relates to a new form of stimulation which may allow simple assessment of an important part of the
vestibular apapratus, the utricle.
Research achievements (from final report):
This series of experiments has extended our knowledge of the function of the vestibular apparatus (inner ear
balance organs), particularly the otolith organs, in both normal subjects and in disease. Achievements include
defining the properties of short latency vestibular reflexes to the eyes and neck evoked by brief lateral
accelerations and the evidence provided that these are likely to be mediated by the utricle (one of two otolith
organs). In addition, evidence has been found for differing resonant frequencies of the two otolith organs
through the tuning properties shown for neck reflexes (cVEMPs) and eye reflexes (oVEMPs). This proposal, if
substantiated, would be an important new finding for human vestibular physiology. We have shown the
changes occurring in short latency VEMPs in three diseases: superior canal dehiscence (in which VEMPs are a
particularly useful diagnostic technique), internuclear ophthalmoplegia (often seen in Multiple Sclerosis) and
vestibular neuritis (inflammation). These techniques have become internationally recognised as an important
new type of vestibular investigation and our current results extend these applications and provide important
new insights into vestibular otolith function in normal humans.
Expected future outcomes:
We expect these findings will prompt further application of VEMPs in diagnosis and in understanding a variety
of diseases affecting the labyrinth (inner ear) and its central pathways.
Name of contact:
Prof Jg Colebatch
Email/Phone no. of contact:
j.colebatch@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 510222
Start Year: 2008
CIA Name: Prof Skye McDonald
End Year: 2011
Admin Inst: University of New South Wales
Grant Type: NHMRC Project Grants
Main RFCD: Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology)
Total funding: $500,938
Title of research award:
Which treatment works? New approaches to treating emotion perception deficits after brain injuryWhich
treatment works? New approaches to treating emotion perception deficits after brain injury
Lay Description (from application):
Many people with traumatic brain injury (TBI) cannot recognise emotions in others. This makes appropriate
social behaviour impossible and leads to isolation and unemployment. In this project we compare training that
minimises errors (errorless learning) versus training that provides strategies for recognising emotions while
allowing errors to occur. Adults with severe TBI will be allocated to one of the two treatments, a social nontherapeutic group or to deferred treatment (waitlist control).
Research achievements (from final report):
, Being able to understand emotional expressions is critical to social competence. We read the emotions of
others in order to respond to them and to monitor their reactions to us. For many people with severe traumatic
brain injuries (TBI) this capacity is lost. This project evaluated treatment approaches to improving emotion
processes in people with TBI, focusing on emotion perception and decision making. In this study we had
several major acheivements:, We compared the efficacy of "errorless learning" where participants are
prevented from making mistakes to "self-instructional" training wherein participants are encouraged to develop
strategies for themselves in several treatment studies. , We developed a professional quality emotion
remediation kit distributed through ASSBI Resources , We examined whether alexithymia (poor self awareness
of emotions), disorders of emotion regulation, poor social decision making and insensitivity to ostracism were
also related to poor emotion perception. This helps us better understand what causes poor emotion perception
to refine targets for remediation. We experimentally manipulated attention as another potential remediation
technique . We also examined emotion perception in both normal adolescents and those with TBI . , The
outcomes for people with TBI will be practical and far-reaching, including:, - Improving their ability to read
and respond to the mood of others;, - Increase their social skills and social opportunities; and, - Lead to a better
quality of life for them, their families and the broader community.
Expected future outcomes:
It is expected that the results of this research will lead to significant improvements in the quality of life for
people with TBI. Specifically, improvements in their ability to read and respond to the moods of others and
their social skills and opportunities.
Name of contact:
Professor Skye Mcdonald
Email/Phone no. of contact:
s.mcdonald@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 510314
CIA Name: Prof Shane Darke
Admin Inst: University of New South Wales
Main RFCD: Central Nervous System
Total funding: $244,858
Start Year: 2008
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
Organic brain damage after non-fatal opioid overdoseOrganic brain damage after non-fatal opioid overdose
Lay Description (from application):
The study will provide the first data on the level and nature of brain damage due to opioid overdose. The extent
to which overdose survivors suffer brain damage has important implications for clinical management,
particularly in relation to behavioural problems. It will also provide the first data on brain damage and drug
treatment performance. Screening of those with an overdose history may lead to specialised management of
these individuals with the potential for improved treatment outcome.
Research achievements (from final report):
Not Available
Expected future outcomes:
N/A
Name of contact:
Professor Shane Darke
Email/Phone no. of contact:
s.darke@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 510326
CIA Name: Prof Skye McDonald
Admin Inst: University of New South Wales
Main RFCD: Central Nervous System
Total funding: $338,422
Start Year: 2008
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
Reinstating emotion perception after brain damage: An experimental approachReinstating emotion perception
after brain damage: An experimental approach
Lay Description (from application):
Many people with traumatic brain injury (TBI) cannot recognise emotions in others. This disrupts social
behaviour leading to isolation and unemployment. In this project we determine whether: (1) selectively
attending to a person's expression improves empathy and emotion recognition; (2) whether mimicking an
expression improves recognition of the emotion and; (3) whether poor recognition of emotional tone of voice
(prosody) and audiovisual displays is improved by focusing on voice or face alone.
Research achievements (from final report):
Being able to understand emotional expressions is critical to social competence. We read the emotions of
others in order to respond to them and to monitor their reactions to us. For many people with severe traumatic
brain injuries (TBI) this capacity is lost. The aim of this project was to examine several theoretically motivated
strategies to improve emotion perception deficits after TBI. We looked at whether poor recognition of
emotional expression is related to a failure to mimic that expression and conversely, whether mimicking can
improve accuracy. We found that people with TBI do fail to mimic but curiously, this is not related to
emotional accuracy although it is related to low self-report lowered empathy. Clearly mimicry does play a
communicative role that is lost post TBI although its exact role remains uncertain. We also examined whether
focusing on emotion in voice (and not the words) increases accuracy. We found that it did not - suggesting that
people with TBI are mainly having trouble recognising tone of voice per se so that is where remediation needs
to focus. These results provide important information to guide remediation efforts for emotion perception
deficits. The finding of impaired mimicry was dramatic. It suggests a basic deficit in affective responses that
might underpin, not only social responsiveness, but also emotion regulation. Emotion regulation is also
commonly disordered after TBI but, to date, very difficult to quantify. Our findings are thus relevant to both
emotiion perception and emotion regulation.
Expected future outcomes:
The results of this research will be used to guide the development of better remediation for emotion perception
and emotion regulation after TBI. This will greatly improve their social skills and psychosocial function and
lead to greater opportunities and quality of life
Name of contact:
Skye Mcdonald
Email/Phone no. of contact:
s.mcdonald@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 510375
CIA Name: A/Pr Richard Fitzpatrick
Admin Inst: University of New South Wales
Main RFCD: Motor Control
Total funding: $420,872
Start Year: 2008
End Year: 2011
Grant Type: Career Development Fellowships
Title of research award:
Human Sensorimotor PhysiologyHuman Sensorimotor Physiology
Lay Description (from application):
We stand without falling by using silent senses from muscles and the balance organs of the inner ear to
unconsciously detect and control our movements. Since the leg muscles provide both the force and the sense,
and critically rely on good circulation, they are vitally important. I propose to study how these sensory and
muscle functions are used to control balance, posture and stepping reflexes, making it easier to identify older
people who will fall and design new preventative strategies.
Research achievements (from final report):
Human balance during standing and walking requires the different senses to be combined properly. This
research investigates the fundamental physiology by which the three senses critical for movement, vision,
proprioception (body sense), and the vestibular sense of gravity create a unified perception of the body in the
world. The research is directed at understanding the causes of falls in older people and identifying specific
strategies to prevent them. A technique has been developed that allows us to stimulate the human vestibular
system electrically. With this we are investigating the sense of self-motion, orientation and balance. We have
shown how signals from the two vestibular organs are combined for balance control and revealed a long-term
adaptation of motion signals within the brain. Studying the proprioceptive sense we have shown that muscle
weakness impairs sensory signals from muscles, an interaction unknown previously and vitally important for
understanding age-related declining function. A major study has shown that the sense of force when muscles
are contracted arises through a return signal from the muscles rather than being generated within the brain
itself, as current theories propose. Applied research has shown that older people at risk of falls have difficulty
knowing when they are vertical and have problems knowing the precise location of objects that they might trip
on. Stepping is a critical reflex that prevents falls. We have identified a range of problems that are associated
with disordered stepping in older people and are progressing with studies to understand the mechanisms and
identify solutions.
Expected future outcomes:
Future work will: (i) identify basic physiology of the human stepping reflex and apply it to the problem of
falling in older people, (ii) use techniques developed to discover how the different sensory systems calibrate
each other, and (iii) explore the origin of the sense of muscular force and fatigue.
Name of contact:
Richard Fitzpatrick
Email/Phone no. of contact:
r.fitzpatrick@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 510385
Start Year: 2008
CIA Name: A/Pr Stuart Smith
End Year: 2012
Admin Inst: University of New South Wales
Grant Type: Career Development Fellowships
Main RFCD: Sensory Processes, Perception and Performance
Total funding: $387,490
Title of research award:
Multisensory determinants of postural instability and falls in older adults; prevention and
rehabilitationMultisensory determinants of postural instability and falls in older adults; prevention and
rehabilitation
Lay Description (from application):
With an increased longevity of the population, age-related health problems, such as falls, are a significant
socioeconomic issue to be addressed. Many sensory systems (e.g. vision, hearing, balance) are known to
gradually become disrupted as a consequence of ageing. This project will investigate the consequences of
declining sensory systems for balance control in older adults and to develop technology to prevents falls in
them.
Research achievements (from final report):
Have developed extensive linkages with industry partners to explore deveopment ofnovel, videogame based
approach to delivering fall risk assessment and fall prevention interventions into the homes of older adults.
Have published 11 peer reviewed articles on the use of technology for fall risk assessment and prevention.
Have estabished an international profile in the development of novel videogame-based approaches to falls in
particular, but health more generally. Have established a very strong national profile for Neuroscience
Research Australia around the application of NBN_enabled technology for delivery of health services.
Expected future outcomes:
Potential commercialisation of technologies developed to deliver fall risk assessment and fall prevention
training into the homes of older adults.
Name of contact:
Stuart Smith
Email/Phone no. of contact:
s.smith@neura.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 525411
CIA Name: Prof Helen Christensen
Admin Inst: University of New South Wales
Main RFCD: Mental Health
Total funding: $835,060
Start Year: 2009
End Year: 2013
Grant Type: NHMRC Research Fellowships
Title of research award:
Uncoupled Research FellowshipUncoupled Research Fellowship
Lay Description (from application):
I am a mental health researcher who designs and tests the effectiveness of methods to encourage help seeking,
to intervene early and prevent the development of psychiatric disorders, and who develops technological tools
to assist consumers to manage their
Research achievements (from final report):
My primary research achievements focussed on developing e health solutions for the early intervention of
anxiety anddepression. This involved the development of web and mobile phone applications which provide
self-help materials based on a variety of therapeutic techniques. A second area was prevention. This focussed
on how mental disorders such as depression and anxiety can be prevented. Prevention is a new area for mental
health. There are challenges that can be overcome to deliver interventions globally efficiently and cost
effectively. A third new area I developed over the course of the fellowship was suicide prevention. This led to a
new stream of work which focussed on trying to make contact with those who do not stay in contact with
mental health services. plus the combining of data sets to examine predictors of low base behaviours the
development of evidence based policy based on priorities for targetting particular groups. The primary
motivation for this research is that the Internet offers unprecedented opportunities to recruit individuals to
research trials a major problem given the low base rate and to disseminate interventions if these are found to be
effective.
Expected future outcomes:
My Fellowship led to the successful application for a John Cade Fellowship which allows me to continue work.
Name of contact:
Helen Christensen
Email/Phone no. of contact:
h.christensen@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 568626
CIA Name: A/Pr Richard Fitzpatrick
Admin Inst: University of New South Wales
Main RFCD: Motor Control
Total funding: $304,099
Start Year: 2009
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
Neurophysiology of human posture and balanceNeurophysiology of human posture and balance
Lay Description (from application):
Whether holding the arm still or standing, the brain uses a silent proprioceptive sense that unconsciously
detects and controls our movements. Key sensory receptors for this sense are located within the muscles that
are also contracting. This is a project to discover how proprioception is affected by muscle contraction and how
this affects postural control. This will improve the management of many common disorders that affect
movement and balance.
Research achievements (from final report):
We have shown how muscle activation both enhances and diminishing proprioceptive sensibility, and a
corresponding effect that muscle weakness impairs sensory signals that arise from muscles making relatively
weaker older adults have worse postural control. A major study has shown that the sense of muscle force arises
through a return signal from muscles rather than from within the brain, as current theories propose. By studying
subjects with a rare sensory loss, it was shown that a central effort mechanism exists and its gain was
measured. However, by fatiguing muscles differently in normal subjects, evidence is provided that a peripheral
signal dominates this sense. By paralysing muscles with curare it was shown that lifted objects feel lighter and
that this is through reafference from muscle spindle, contrary to current theories of spindle function. This result
is the target of current and planned studies. We have shown that the ability to control posture depends on the
elastic stiffness of the load being held and how muscle and tendon contribute to this. By muscle ultrasound, it
was shown that there is no simple relationship between muscle length and joint angle but that it is a dynamic
function of frequency depending strongly on load stiffness. At resonance, the load and joint oscillate on the end
of a compliant tendon without significant transfer of movement to the contractile portion, thus constituting an
effective proprioceptive and control blind spot. This muscle-tendon behaviour is a major determinant of muscle
reflexes and sets limits on human postural control.
Expected future outcomes:
Future work will: (i) explore the origin of the sense of muscular force and fatigue, (ii) explore the mechanisms
of adaptation in proprioceptive sensation identified in this project, and (iii) use techniques developed to
discover how the different sensory systems calibrate each other, .
Name of contact:
Richard Fitzpatrick
Email/Phone no. of contact:
r.fitzpatrick@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 568637
CIA Name: Dr Gila Moalem-Taylor
Admin Inst: University of New South Wales
Main RFCD: Peripheral Nervous System
Total funding: $470,052
Start Year: 2009
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
The role of proinflammatory interleukin-17 (IL-17) and IL-17-producing T cells in neuropathic painThe role of
proinflammatory interleukin-17 (IL-17) and IL-17-producing T cells in neuropathic pain
Lay Description (from application):
Peripheral nerve injury often results in persistent and debilitating neuropathic pain. My overall objective is to
understand the immunological mechanisms responsible for such pain. I plan to test the hypothesis that the
proinflammatory cytokine interleukin-17 promotes neuroinflammation and contributes to increased pain
sensitivity after nerve injury. This study promises to enhance our understanding of neuroimmune activation in
neuropathic pain and offers new opportunities for pain management.
Research achievements (from final report):
Neuropathic pain is a chronic pain caused by a lesion or disease of the somatosensory nervous system and
characterised by debilitating sensory abnormalities and increased pain sensitivity. Neuropathic pain affects 5%
of the general population, causes substantial disability, and lacks adequate treatments. Recent studies have
demonstrated that small signaling protein molecules, termed cytokines, play an important role in the
neuroimmune processes of neuropathic pain. In particular, an imbalance between algesic proinflammatory
cytokines and analgesic anti-inflammatory cytokines has been implicated. The fundamental aim of this research
is to elucidate basic immunological mechanisms responsible for neuropathic pain, with particular reference to
the role of the proinflammatory cytokine interleukin-17 (IL-17) in neuroinflammation and pain hypersensitivity
following injury to the nervous system. We found that mice deficient in IL-17 have significantly decreased
mechanical pain hypersensitivity as well as decreased infiltration of leukocytes to the injured nervous system
tissue following nerve injury. Further, administration of IL-17 into the hind-paw and the sciatic nerve of intact
animals caused pain hypersensitivity associated with significant inflammatory response. In addition, we found
that mice deficient in IL-17 have better locomotor recovery, smaller lesion size and decreased inflammatory
cell infiltration following spinal cord contusion injury. In summary, we have demonstrated an important role
for IL-17 in regulating neuroinflammatory responses, thus contributing to neuropathic pain after peripheral
nerve injury and secondary degeneration after spinal cord injury. This work identifies IL-17 as a potential
therapeutic target in neuropathic pain due to peripheral nerve injury and in recovery from spinal cord injury.
Expected future outcomes:
This study significantly enhances our understanding of the involvement of cytokines in nervous system injury
and offers hope for new approaches to therapeutic intervention by means of immune modulation. In particular,
new biologic drugs that block IL-17 may prove useful in the treatment of neuropathic pain and spinal cord
injury.
Name of contact:
Gila Moalem-Taylor
Email/Phone no. of contact:
gila@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 568700
Start Year: 2009
CIA Name: Prof Simon Gandevia
End Year: 2011
Admin Inst: University of New South Wales
Grant Type: NHMRC Project Grants
Main RFCD: Neurosciences not elsewhere classified
Total funding: $475,152
Title of research award:
NOVEL CENTRAL MECHANISMS IN HUMAN PROPRIOCEPTIONNOVEL CENTRAL MECHANISMS
IN HUMAN PROPRIOCEPTION
Lay Description (from application):
Proprioception is how we sense the position of our joints, the movements of our joints, and the forces generated
by our muscles. Disturbances of proprioception can cause major disruption of all movements and postures.
We will undertake novel studies of how signals generated in the brain which command our movements
contribute to all key aspects of proprioception. Finally we will unravel how the brain builds up the overall
'scheme' of our body which we need to make any accurate movement.
Research achievements (from final report):
The proprioceptive senses are critical for the performance of volitional tasks. These sensations must function
properly to allow normal control of movements and postures. Overall we aimed to determine novel neural
mechanisms underlying proprioception as this will provide insight into movement execution and its clinical
disturbances. A key feature of the first two aims of the grant was to assess the role of centrally generated
command signals in specific component sensations of human proprioception. Such signals are known to
contribute to force sensation but their role in other components in controversial., We have shown using local
paralysis with curare-like compound that motor command signals bias the sense of joint position when the
usual afferent proprioceptive signals are intact. This proprioceptive effect was graded with the level of motor
command. Other data also supported this view. We have determined that signals of command also generate
sensations of movement using ischaemic anaesthesia and paralysis to produce a phantom hand. , We examined
the illusory overestimation of force that occurs when it is generated passively on the skin compared with when
it is generated actively. Our work suggests that this force overestimation may have an alternative explanation to
the conventional one (based on a simple 'cancellation' model). , To understand the body image, we studied
experimental 'phantoms' produced by ischaemia. We have shown that there is not a default position of a
phantom arm. Further studies are underway.
Expected future outcomes:
This project has opened the way for new work on the lilnk between the 'body image' and proprioception. The
link is crucial for all our voluntary movements.,
Name of contact:
Professor Simon Gandevia
Email/Phone no. of contact:
s.gandevia@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 568702
CIA Name: A/Pr Janet Taylor
Admin Inst: University of New South Wales
Main RFCD: Motor Control
Total funding: $331,390
Start Year: 2009
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
Neural aspects of human muscle fatigueNeural aspects of human muscle fatigue
Lay Description (from application):
Muscle fatigue is common after exercise in healthy people. In many tasks, some muscles become more fatigued
than others. Thus, the nervous system must often coordinate fatigued muscles (which produce less force) with
unfatigued muscles. We will investigate how fatigue of one muscle alters the way the brain controls other
muscles that are engaged in the same task or in unrelated tasks. This will aid understanding of the failures of
coordination that lead to poor performance and injury.
Research achievements (from final report):
, Fatigue produced by exercise involves changes in muscle itself but also in the nervous system at spinal and
cortical levels. The "central" contribution to fatigue is substantial and is particularly prominent during
sustained weak contractions. Studies in this project developed a new way to examine the behaviour of the
motor nerve cells in the human spinal cord while participants perform fatiguing muscle contractions. This
technique showed that the motor nerve cells become harder to activate with fatigue and that this likely depends
on repetitive activity of the cells. This suggests that mechanisms at a spinal level contribute to fatigue with
exercise, whereas testing of the brain region that controls movement did not show changes that would lead to
reduced output. Other studies examined the contribution of sensory feedback from the muscle on people's
ability to drive the muscles maximally. Contrary to expectations, muscle pain produced experimentally was
found to have surprisingly little effect on the ability of people to produce muscle force. However, sensory
feedback related to fatigue did reduce drive to the muscle, and this occurred whether the feedback came from
the tested muscle or a different muscle in the limb. These results suggest that sensory feedback related to
metabolites produced by muscle work contributes more generally to central fatigue and that the pathway
conveying muscle pain may differ from that conveying fatigue sensations.
Expected future outcomes:
Understanding the specific mechanisms which lead to fatigue with exercise is important in directing
interventions for patients who suffer excessive fatigue in performing the tasks of daily life (e.g. after stroke or
cancer), as well as directing exercise for fitness in the general population and maximising athletic performance.
Name of contact:
Janet Taylor
Email/Phone no. of contact:
j.taylor@neura.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 568724
CIA Name: Prof Stephen Lord
Admin Inst: University of New South Wales
Main RFCD: Preventive Medicine
Total funding: $390,394
Start Year: 2009
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
Development of a novel intervention for training stepping ability to reduce the risk of falls in older
adults.Development of a novel intervention for training stepping ability to reduce the risk of falls in older
adults.
Lay Description (from application):
Stepping is often the last protective option to prevent a fall. This study will first modify and validate an
interactive system for training stepping ability in older adults. The system will be also provide the capability
of acquiring indeices of stepping ability in the home. We will investigate the effect of an in-home training
program using this system on stepping ability and falls risk. Findings will inform future interventions for
preventing falls.
Research achievements (from final report):
This project has enabled us to develop and evaluate a novel telehealth technology for delivery of strength and
balance training exercses to reduce the risk of falls directly into the homes of older adults. Furthermore our
technology will enable remotely located researchers and clinicians to track indices of fall risk at regular
intervals overtime. Our technology has leveraged existing exercise-based videogame technology that is readily
available to the consumer. As such we are beginning to explore a method for delivering fal prevention training
programs at scale. , We have established that the way in which older adults play exercise videogames, like a
modified version of Dance Dance Revolution, suggests the possibility for tracking a proxy measure for fall risk
over time. Results of our initial exploration of this have been published in the British Journal of Sports
Medicine, 45(5), 441-445, Furthermore, we have been able to develop a technology solution based on Dance
Dance Revolution that enables us to measure a correlate of fall risk, previously only possible from laboratorybased measurement, in the homes of older adults. We have published a validity and reliability study of a dance
mat-based Choice Stepping Reaction Time (CSRT) test in the Archives of Physical Medicine and
Rehabilitation, 92(6), 947-953., In a recent pilot study where we randomised older adults into an 8-week step
training intervention or usual care control group, participants completing the intervention (n=15) were
significantly faster on the CSRT measure of stepping performance and performed better on sway and contrast
subtest of the Physiological Profile Assessment for fall risk that those participants completing in the control
(n=17). In the intervention group around half also self reported improvement in balance confidence (8/15) and
balance performance(7/15). No adverse incidents were reported suggesting that our approach is a safe method
for delivering unsupervised fall prevention training.
Expected future outcomes:
We aim to extend these initial investigations to address dose-response effects on fall risk. We also aim to
address the effect of building social connectivity tools around the step training system to increase compliance
with exercise interventions. Our technology can be translated to other research questions and we are currently
looking to trial our device in people living with Multiple Sclerosis.
Name of contact:
Stuart Smith
Email/Phone no. of contact:
s.smith@neura.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 568769
Start Year: 2009
CIA Name: Dr Nicole Jones
End Year: 2012
Admin Inst: University of New South Wales
Grant Type: NHMRC Project Grants
Main RFCD: Pharmacology not elsewhere classified
Total funding: $293,230
Title of research award:
Hypoxia-inducible factor-1 (HIF-1): Pharmacological and molecular insights into its role in brain
protectionHypoxia-inducible factor-1 (HIF-1): Pharmacological and molecular insights into its role in brain
protection
Lay Description (from application):
At present, there are no effective therapies for reducing brain damage which can occur after acute brain insults
including birth asphyxia. This project aims to study whether increasing a naturally occurring protective protein
(HIF) in the brain can minimize brain damage in a model of perinatal brain injury. We plan to validate HIF as
a novel therapeutic target for reduce brain injury and promote brain repair processes.
Research achievements (from final report):
, Hypoxia is an important feature of many neurological conditions. While severe hypoxia causes brain cell
death, it is known that exposure to mild hypoxia can induce tolerance and protect the brain against a
subsequent injury. Key events in this protective phenomenon are regulated by the transcription factor hypoxiainducible factor-1 (HIF-1), its regulatory enzymes (HIF-1 prolyl hydroxylases (PHDs)) and its many target
genes. , - We showed that two of the PHD inhibitors tested ((DFX), and EDHB)) can protect astrocytes, via
increasing HIF-1 and VEGF and this work resulted in 1 publication (Chu et al, 2010)., - We also found that a
number of PHD inhibitors tested in vivo (EDHB, DFX, CoCl2) can reduce brain tissue loss at 5 days after HI
injury . , - Studies have also determined that expression of PHD enzymes are differentially altered in response
to HI injury, and PHD3 appears to be involved with cellular injury process. , - Post injury treatment with
EDHB (200mg/kg) can improve long term functional impairment up to 5 weeks after HI injury and may also
affect cell proliferation.
Expected future outcomes:
We have 1 published manuscript and a book chapter based on work generated by this grant and we have 3
additional manuscripts in preparation.
Name of contact:
Nicole Jones
Email/Phone no. of contact:
n.jones@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 570872
CIA Name: Prof Rob Herbert
Admin Inst: University of New South Wales
Main RFCD: Health and Community Services
Total funding: $221,873
Start Year: 2009
End Year: 2013
Grant Type: NHMRC Project Grants
Title of research award:
Passive mechanical properties of muscle fascicles and tendons of people with contracture and healthy
controlsPassive mechanical properties of muscle fascicles and tendons of people with contracture and healthy
controls
Lay Description (from application):
Muscle contracture - abnormal stiffening of muscles - is common in many conditions, including stroke, spinal
cord injury and multiple sclerosis. Contractures can be very disabling. The mechanisms of muscle contracture
are poorly understood. This study will determine whether contractures of calf muscles in people with stroke,
spinal cord injury and multiple sclerosis are due to changes in the mechanical properties of muscle fascicles or
tendons.
Research achievements (from final report):
A new method was developed for non-invasive measurement of the passive length-tension properties (i.e.,
extensibility) of human muscles in vivo. This method was used to show that people who have ankle
contractures after stroke have muscles that are stiffer, but not shorter, than control subjects who do not have
contracture. Incidental findings suggested a previously unrecognised mechanism that determines the passive
properties of skeletal muscles in vivo.
Expected future outcomes:
The findings may lead to a new understanding of the determinants of the passive properties of human muscles,
and might ultimately provide insights into the nature of contractures which are a major cause of disability.
Name of contact:
Professor Rob Herbert
Email/Phone no. of contact:
r.herbert@neura.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 571178
CIA Name: Dr Wei Du
Admin Inst: University of New South Wales
Fellowships
Main RFCD: Epidemiology
Total funding: $349,407
Start Year: 2009
End Year: 2012
Grant Type: International Exchange Early Career
Title of research award:
Translation of effective interventions in injury prevention and trauma care to a Chinese settingTranslation of
effective interventions in injury prevention and trauma care to a Chinese setting
Lay Description (from application):
Evidence informed injury policy is not currently well developed in China. This research project will provide
measures of the effectiveness of both a trauma care protocol in a hospital setting, and an intervention program
for novice driver education/training in China, and will therefore contribute to the building of an evidence based
injury prevention capacity in China.
Research achievements (from final report):
The project aims to address a major and growing public health problem in China, road trauma, by a partnership
between Australian experts with internationally recognized track records in road safety research and key
Chinese agencies and Chinese researchers. Road trauma is emerging as a leading cause of death, disability, and
injury in China, and this is forecast to increase, as China is under rapid motorization. Reducing road trauma, by
translating effective interventions in road trauma prevention into the current Chinese setting, where proper
knowledge, legislation, and practice are missing, is thus a high priority for global health. Specifically, this
project has two key components, i.e., 1) developing and implementing a cost-effective kindergarten based
parental educational intervention to encouraging the correct use of age appropriate child restraints for young
children while travelling in cars; and 2) developing and evaluating an on-road driver education and training
program to reduce novice driver crashes. Both programs were trialed in Beijing of China, and if successful,
they could be straightforwardly extended to other similar settings across China.
Expected future outcomes:
The compulsory use of child restraint for young child car passengers is expected to be trialed in Shanghai soon,
and nation wide legislative change as to the introduction of compulsory child restraint use is currently under
review.
Name of contact:
Wei Du
Email/Phone no. of contact:
kelvindu@gmail.com
NHMRC Research Achievements - SUMMARY
Grant ID: 632921
CIA Name: A/Pr Teresa Senserrick
Admin Inst: University of New South Wales
Main RFCD: Epidemiology
Total funding: $394,460
Start Year: 2010
End Year: 2013
Grant Type: Career Development Fellowships
Title of research award:
Road traffic injury prevention among disadvantaged youth, Indigenous communties and low income
countriesRoad traffic injury prevention among disadvantaged youth, Indigenous communties and low income
countries
Lay Description (from application):
Media Summary not available
Research achievements (from final report):
Road traffic injuries are a leading cause of death globally and the leading reason young Australians die or
acquire a disability in Australia. I contributed to research showing that while young driver deaths are
decreasing, this is only true in urban areas (not rural or remote areas) and disadvantaged youth are over
involved. I identified several new reasons why young drivers crash and determined which of several current
initiatives could reduce their crashes and what policies for licensing from learner to provisional to full licence
were best. I found Aboriginal and Torres Strait Islander injury prevention programs were scarce and not wellevaluated and was able to show best practice road safety approaches could be applied even in remote
Aboriginal communities. I helped conduct the first representative road safety survey of Aboriginal people and
advised on a new licensing suport program. These findings will help with policy and practice developments
that will reduce young driver crashes and disabilities in Australia, with this work also shared internationally. I
also developed a training program to help new drivers in China, with this and other changes in licensing policy
helping reduce new driver crashes in China.
Expected future outcomes:
This work helped promising Australian initiatives for reducing young driver crashes to receive on-going
funding and for licensing policy changes to be considered that should significantly reduce youth crashes and
injuries in the future. New support programs for disadvantaged learners and Aboriginal people will help them
get a driver licence.
Name of contact:
Teresa Senserrick
Email/Phone no. of contact:
t.senserrick@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 1000674
CIA Name: A/Pr Leslie Foster
Admin Inst: University of New South Wales
Main RFCD: Medical Devices
Total funding: $213,125
Start Year: 2010
End Year: 2011
Grant Type: NHMRC Development Grants
Title of research award:
Application of Sutureless Technology 'SurgiLux' for Dura Mater Repair: A Proof of Concept StudyApplication
of Sutureless Technology 'SurgiLux' for Dura Mater Repair: A Proof of Concept Study
Lay Description (from application):
A unique technology that combines biomaterials and lasers to effectively close and seal wounds could replace
sutures in delicate surgery close to the brain. Wound closure in the cranium is still reliant upon sutures or
'stitches' and these have complications; a major one being leakage of cerebro spinal fluid (CSF). The
application of 'SurgiLux' technology will both close and seal these wounds quickly and easily, with significant
health and economic benefits.
Research achievements (from final report):
Current procedures for the closure of the dura mater remain reliant upon sutures. Leakage of cerebrospinal
fluid (CSF) is a common and expensive complication of certain operations that often requires inclusion of
prophylactic preoperative lumbar drains. CSF leakage is associated with high additional costs while research
has shown that a significant reduction of these costs can be achieved through the use of sealants. However,
despite considerable research in the area, commercial adhesives and sealants are inappropriate and unused.
Thus, there is an identified health requirement for a surgical device to effectively close and seal the dura mater
after surgery. Thin films of 'SurgiLux' were found to readily seal incisions in the dura mater and prevent
leakage. Irradiation of the SurgiLux with a near-infrared laser effectively bound the film to the tissue while
showing no thermal damage. The procedure of cutting SurgiLux to size and its irradiation were found to be up
to seven times faster than the current procedure using sutures. However, feedback from surgeons and research
results have highlighted the requirement for the development of a pulse laser system to reproduce these results
using current surgical procedures.
Expected future outcomes:
results have highlighted the requirement for the development of a pulse laser system to reproduce these results
using current surgical procedures.
Name of contact:
A/Prof. L.J.R. Foster
Email/Phone no. of contact:
J.Foster@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 100967
CIA Name: A/Pr Amanda Baker
Admin Inst: University of Newcastle
Main RFCD: Psychiatry
Total funding: $217,465
Start Year: 2000
End Year: 2002
Grant Type: NHMRC Project Grants
Title of research award:
Evaluation of cognitive-behaviour therapy for alcohol and other drug problems among people with a psychotic
illnessEvaluation of cognitive-behaviour therapy for alcohol and other drug problems among people with a
psychotic illness
Lay Description (from application):
Abuse of alcohol and other drugs among people with a major psychiatric illness is a serious public health
problem and cost-effective treatments need to be developed and assessed. The aim of this project is to evaluate
the effectiveness of a counselling intervention. 180 individuals with a psychotic illness and concurrent alcohol
and other drug (AOD) problems will be randomly assigned to counselling or usual treatment and followed up
for a period of 12 months. The indicators of interest include: current drug use; psychiatric symptoms; selfharm; social functioning; and use of health services. Findings from the proposed study will assist in the
selection of particular treatment strategies and will aid the overall development of services for people with both
major mental illness and substance abuse.
Research achievements (from final report):
This trial has led to significant advances in research design for people with co-occurring psychotic illness and
drug and alcohol problems. It has highlighted the co-occurrence and treatability of the specific co-occurring
condition of cannabis and psychosis and has indeed seeded a further postgraduate research project in this area. ,
It is important that the treatment offered in this trial be transferred into routine clinical practice, particularly
among cannabis users who have a psychotic condition. The treatment evaluated in this trial offered an
integrated approach, where mental health problems (psychosis) and drug and alcohol use were addressed
within the one framework. This integrated approach warrants further examination., The results of this trial have
helped inform future research directions, whereby the team will be evaluating a stepped care approach to
treating co-occurring mental health and drug and alcohol conditions, so that treatment is stepped up according
to response.,
Expected future outcomes:
CONCLUSION:, There was a strong retention rate over
the 10 treatment sessions with a typically challenging sample, with evidence of overall improvement over time
for alcohol consumption, poly-drug use and an aggregate hazardous day's use score. There was evidence of
improvement by group for cannabis, amphetamine, depression and global functioning.
Name of contact:
Dr Amanda Baker
Email/Phone no. of contact:
(02) 49246605
NHMRC Research Achievements - SUMMARY
Grant ID: 351140
CIA Name: Prof Leonie Ashman
Admin Inst: University of Newcastle
Main RFCD: Oncology and Carcinogenesis
Total funding: $454,500
Start Year: 2005
End Year: 2007
Grant Type: NHMRC Project Grants
Title of research award:
Role of the tetraspanin CD151 in epithelial biology and cancerRole of the tetraspanin CD151 in epithelial
biology and cancer
Lay Description (from application):
A cell surface protein identified in this laboratory has been linked to cancer progression and metastasis. This
project aims to examine the molecular basis of the action of the protein in regulating cell migration, and to
establish model systems to provide definitive evidence as to its role in the development and progression of
cancer. The models will also provide systems for future studies to evaluate the potential of antibodies and
other inhibitors of the action of this protein as therapeutics in a range of human cancers.
Research achievements (from final report):
This project used resources (monoclonal antibodies, gene knock-out mice) previously developed in the
laboratory to investigate the function of the CD151 protein in vivo. The most significant results were
demonstration of a role for CD151 in skin wound healing and in kidney function. These studies were
complemented by analysis of CD151 function in tissue culture models. The CD151 gene knock-out was backcrossed for 10 generations onto a different mouse strain suitable for analysis of the role of CD151 in breast and
prostate tumour initiation and progression and these experiments were initiated.
Expected future outcomes:
This and follow-on projects will improve our understanding of mechanisms of tissue repair and tumour
metastasis and will lead to new biomarkers for classification of breast and prostate cancer and potentially new
approaches to treatment. The unexpected demonstration of a role for CD151 in kidney function will be
followed up and should give new insights into the pathogenesis of human renal disease
Name of contact:
Professor Leonie Ashman
Email/Phone no. of contact:
leonie.ashman@newcastle.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 401244
CIA Name: Prof Robert Callister
Admin Inst: University of Newcastle
Main RFCD: Sensory Systems
Total funding: $441,473
Start Year: 2007
End Year: 2008
Grant Type: NHMRC Project Grants
Title of research award:
Descending control of pain pathwaysDescending control of pain pathways
Lay Description (from application):
Current treatments for chronic pain are limited in their success. This emphasises the need for new insights into
the basic mechanisms and nervous system circuitry underlying altered or chronic pain states. Work in animals
and patients with chronic pain shows that certain brainstem centres communicate, via descending spinal cord
pathways, with small nerve cells in the superficial dorsal horn (SDH) of the spinal cord. These SDH neurones
receive and process pain-signalling information from the skin and internal organs, and receive inputs from
descending pathways. This descending input can either inhibit or enhance the activity of SDH neurones and
subsequent pain perception. Till now it has been difficult to "directly" examine how descending pain pathways
influence the small SDH neurones in the spinal cord. A new approach, which has been developed in our
laboratory, now allows us to record from these very small SDH neurones in the spinal cord of an intact deeply
anaesthetized mouse. In addition, our technique allows us to examine the recorded SDH neurone s responses
to functionally relevant stimuli (brushing or pinching the hindpaw) as well as its physiology and anatomy. This
project will use our new techniques to examine the effects of activating descending brainstem pathways that
alter the way painful stimuli are processed in the spinal cord. The effects of altered levels of inhibition in the
spinal cord will also be studied by using mice with naturally occurring mutations in their inhibitory glycine
receptors. We believe a more complete understanding of pain processing mechanisms will be achieved by
examining the role of descending pathways in an intact animal preparation. Such data are essential for the
development of drug therapies that can successfully target pain syndromes.
Research achievements (from final report):
This focus of this application was to study the effects of stimulating nerve fibres, originating in the brain or
skin, on the responses of nerve cells in the region of the spinal cord involved in pain. We can now do this
routinely in the laboratory mouse. Because the mouse is the species of choice for genetic technologies (ie,
making transgenic and knockout mice) the methods and results of the project have tremendous potential for
exploring the roles of genes in pain processing. Major outcomes were:, 1) We can now routinely obtain
recordings from spinal neurons AND record their responses after stimulating nerve cells in the brain or
periphery of the mouse., 2 We know how recording temperature affects responses of spinal neurons. This is
important, as a major goal of this project was to relate new information recorded intact animals (ie, in vivo at
37 degrees C) to the huge literature obtained in spinal cord slices (recorded at 23 degrees C)., 3) We have also
published the first study where the effects of a genetic mutation are examined in single neurons within the
nervous system of an intact mouse., 4) We also developed a horizontal spinal cord slice preparation that allows
recording in spinal cord neurones while stimulating pathways from the barin. This preparation will be
invaluable for future detailed pharmacological analysis of the synaptic mechanisms at connections between
brainstem and SDH neurones. This sort of analysis cannot be carried out in slice preparations. , 5) We have
established when, during development, the circuitry and neurons within the SDH can be considered
functionally mature., 6) Written a major review on the spinal neurons involved in pain processing.
Expected future outcomes:
We will continue to use our in vivo mouse preparation to examine the effects of altered genes on spinal cord
pain processing mechanisms.
Name of contact:
Robert Callister
Email/Phone no. of contact:
NHMRC Research Achievements - SUMMARY
robert.callister@newcastle.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 455527
Start Year: 2007
CIA Name: A/Pr Jonathan Hirst
End Year: 2009
Admin Inst: University of Newcastle
Grant Type: NHMRC Project Grants
Main RFCD: Foetal Development and Medicine
Total funding: $450,703
Title of research award:
Neurosteroid mediated protection after birth: approaches for maximising protective steroid levels in the
neonatal brainNeurosteroid mediated protection after birth: approaches for maximising protective steroid levels
in the neonatal brain
Lay Description (from application):
Complications during pregnancy, birth asphyxia or premature birth can lead to neurological impairment in the
newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neurosteroids
are a group of steroids that regulate brain activity. These steroids protect brain cells from damage caused by an
inadequate supply of oxygen by suppressing toxicity caused by excessive activity. We have shown that the
levels of these protective steroids are remarkably high in the fetal brain and levels rise further in response to
fetal stress. The placenta contributes steroid precursors that help maintain these high neurosteroid levels. This
placenta-fetal brain interaction comprises an internal mechanism that protects the fetal brain from adverse
events during pregnancy. At birth, however, there is a dramatic decline in neurosteroid concentrations in the
brain after the loss of the placental precursor supply. The fall in concentrations is even greater in animals that
are born growth restricted. This suggests that newborns, particularly those from compromised pregnancies, are
at increased risk of brain damage due to low neurosteroid levels. We believe that certain commonly used
steroid therapies may also lower steroid levels in the brain and result in increased vulnerability to brain damage
during birth or in the early neonatal period. Alternatively, we propose that replacement of neurosteroid
precursors in the newborn may raise brain neurosteroid levels and protect against brain damage. In the
proposed studies we will evaluate treatments that can raise the concentration of steroids and determine the best
strategy for reducing brain injury following complications during pregnancy, at birth and during the early
newborn period. This work will determine the best therapeutic approaches for maximising neurosteroidinduced brain protection and for reducing the risk of brain damage.
Research achievements (from final report):
The objectives of the work were to examine the neurosteroid responses at the fetal to neonatal transition
and to determine if these responses are required for neuroprotection and are defificent in compromised
pregnencies. This work required the establishment of a model of intrauterine growth restriction (IUGR) in
guinea pigs. We found that of growth restriction reduced levels of key 5alpha-reductase enzymes, in the
placenta and brain. This result suggests that reduced expression in the brain may continue after birth and lead
to the reduced neurosteroid levels neonates. We also found if neurosteroid production was reduced by 5alphareductase inhibition there was a marked increase in cell death in the fetal brain supporting a neuroprotective
action for these steroids. We also established a model of birth asphyxia that markedly increased apoptotic cell
death in the brain if the fetus was already growth restricted. We found that administration of allopregnanolone
prevented the asphyxia-induced increase in cell death and improved outcome after asphyxia in the IUGR fetus.
We then explored if preterm birth leaves the neonatal brain more vulnerable to hypoxia due to reduced
neurosteroid synthesis. We found that the expression of both 5alpha-reductase isoforms was lower in the
human placenta collected after preterm labour, suggesting that preterm birth increases the risk of brain injury
due to the lower neurosteroid exposure. Together, this suggests that the preterm neonate may be at risk of brain
injury due to their lower capacity to produce neurosteroids around the time of birth. The more marked effect
we found with male fetuese may explain their greater vulnerability.
Expected future outcomes:
, , , The results of this project support the proposal that steroid supplementation may be valuable in protecting
the brain after preterm birth. Future studies will evaluate different steroid treatments. We showed that the
preterm neonates have deficient in neurosteroid concentrations in the brain increasing vulnerability to siezures,
which could be treated using neurosteroid replacement.
NHMRC Research Achievements - SUMMARY
Name of contact:
Jonathan Hirst
Email/Phone no. of contact:
Jon.Hirst@newcastle.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 569206
CIA Name: Prof Robert Callister
Admin Inst: University of Newcastle
Main RFCD: Systems Physiology
Total funding: $469,768
Start Year: 2009
End Year: 2012
Grant Type: NHMRC Project Grants
Title of research award:
Spinal mechanisms underlying neck painSpinal mechanisms underlying neck pain
Lay Description (from application):
Chronic neck pain is difficult to treat and can result in a complex set of symptoms, including dizziness,
disturbed vision, and exaggerated pain responses in the upper torso and arms. Thus, there is a need to develop
new treatments for this debilitating condition. This project will study how damage to structures in the neck
alters the excitability of nerve cells in the upper cervical spinal cord. The results will provide a foundation for
development of therapies to treat chronic neck pain.
Research achievements (from final report):
This project asked whether the properties of spinal neurons that process sensory information differs in the
upper cervical and lumbar spinal cord under normal conditions and following inflammation. Our results show
the intrinsic properties of these nerve cells are generally concerved across spinal cord segments, however,
nerve cells in the upper cervical cord differ in the expression of potassium channels and the way they fire
action potentials. When structures in the neck are inflammed nerve cells in the upper cervical cord are clearly
activated, yet their intrinsic properties are unchanged by acute inflammation. Together these data suggest the
intrinsic properties of neurons in the spinal cord are not as suseptible to the well-characterised plasticity that
occurs in synaptic inputs. These data will be of use for future modelling of the responses of spinal circuits to
altered input from the periphery. In essence, the contribution of intrinsic properties to altered information flow
through the part of the spinal cord involved in pain signalling can be considered as realtively constant or
unchanging. During the course of this study we also showed that one of the ion channels that determines the
intrinsic properties of SDH neurons, a type of hyperpolarisation-activated current (Ih), may serve as an
"anatomical" marker for neuronal populations that fire tonically. Such neurons comprise >50% of the neurons
in the spinal cord dorsal horn and our data now provide a method to identify these cells quickly and at the
population level of analysis.
Expected future outcomes:
We have now established a baseline dataset on the properties of spinal neurons that receive information from
stuctures in the neck. These data are essential for future studies on the response of spinal circuits to peripheral
insults.
Name of contact:
Robert J Callister
Email/Phone no. of contact:
robert.callister@newcastle.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 569265
CIA Name: Prof Kypros Kypri
Admin Inst: University of Newcastle
Main RFCD: Epidemiology
Total funding: $408,413
Start Year: 2009
End Year: 2012
Grant Type: Career Development Fellowships
Title of research award:
Reducing the injury and disease burden attributable to alcohol: methodological, aetiological and intervention
studies.Reducing the injury and disease burden attributable to alcohol: methodological, aetiological and
intervention studies.
Lay Description (from application):
The research examines the influence of individual, social and environmental factors on drinking behaviour, and
seeks to determine the effectiveness of strategies to prevent alcohol-related harm, with a particular focus on
youth drinking. A series of studies is proposed, examining the validity of methods for measuring drinking
behaviour; social and environmental factors, and interventions. The findings will have relevance to reducing
the burden of alcohol-related injury and disease in Australia.
Research achievements (from final report):
The Award enabled a programme of research in four interconnected streams focussed on the epidemiology and
prevention of alcohol-related disease and injury, namely: Methodology, Prevalence and Risk Factors,
Intervention Trials, and Policy Evaluation. National and international competitive grants were obtained to
conduct studies in each stream. Highlights include a series of experimental studies of Research Participation
Effects, a novel conceptualisation of ways in which aspects of study design and implementation can bias the
identification of disease risk factors, and estimates of intervention effect. A world-first cohort of 2000 childparent dyads was established and to investigate the role of parental supply of alcohol on adolescent risky
drinking. A world-first clinical trial of web-based alcohol screening and brief intervention for hospital
outpatients was initiated. An epidemiological investigation of the effects of changes in pub trading hours on
assault rates was conducted, and an evaluation of the effects of reducing the alcohol minimum purchasing age
in New Zealand was initiated. The findings were disseminated in 45 papers, reviews, and commentaries
published predominantly high impact general medical, public health and addiction journals; to practitioner and
professional groups, policy makers, and the general public via national news media. There were demonstrable
changes to policy and preventive medical practice arising from the research. Several academic staff and
postgraduate students received training through their involvement in the research programme, including
substantial involvement in the acquisition of competitive grants, publications, and research translation. The
work was recognised in a prestigious international award and served as the basis of a successful application for
a NHMRC Senior Research Fellowship.???
Expected future outcomes:
The research initiated during the Award period continues and has given rise to new projects including an
epidemiological study of the longer term effects of restrictions in pub trading hours; and pilot research on the
provision to hospital outpatients of genetic feedback on risks for alcohol dependence and certain cancers to
reduce unhealthy alcohol consumption.
Name of contact:
Professor Kypros Kypri
Email/Phone no. of contact:
Kypros.Kypri@newcastle.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 142931
Start Year: 2001
CIA Name: Prof Jenny Strong
End Year: 2003
Admin Inst: University of Queensland
Grant Type: NHMRC Project Grants
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $105,794
Title of research award:
Inter-rater reliability and predictive validity of a new functional capacity evaluation for chronic back painInterrater reliability and predictive validity of a new functional capacity evaluation for chronic back pain
Lay Description (from application):
Back pain costs the Australian community tens of billions of dollars. Back pain is one of the main causes of
work injury and lost time from work. The longer a person is off work, the harder it is to get them back to work.
Workers' compensation systems around Australia aim at getting the injured worker with back pain back to
work as soon as possible. One of the difficulties in this process is determining what the person with back pain
can physically do in the workplace. An evaluation technique, called functional capacity evaluation (known as
FCE), is one method used to find out what the person with back pain physically can and cannot do. In a FCE, a
trained health professional such as an occupational therapist, observes the person performing a range of
physical activities like the ones he or she may have to perform in a job. The therapist closely observes the
person performing activities such as lifting, carrying, kneeling, crouching, balancing, and walking and notes
any limitations in the person's ability to complete the activities. The therapist makes comments about what
difficulties the person may have on the job and recommendations about how these could be reduced or
eliminated. The information gained from these evaluations can be valuable for the treating doctor in deciding
whether the person is ready to go back to work and what duties the person can and cannot do on the job.
Because of such value they provide, FCE is commonly used in rehabilitation programs endorsed by workers'
compensation systems around Australia. This widespread use and endorsement of FCE occurs despite limited
research on the soundness of the ratings made from these evaluations. There is a need to see whether
recommendations made from FCEs are consistent between therapists (i.e. reliable) and to see if the FCE
accurately predicts the person's physical capacity for work. This research will examine these issues with injured
workers with back pain.
Research achievements (from final report):
This project has made a major advance in the development of a new, safe and reliable approach to evaluating
the ability of people with back injuries causing pain, to return to the workforce. The approach, known as the
Gibson Approach to Functional Capacity Evaluation, or GAPP FCE, has now been through a series of tests,
using both healthy volunteers and people with back injuries, and has been found to be both safe to use and to
provide a reliable evalaution. Functional capacity evaluation is an important tool for rehabilitation
professsionals who assist workers who have had injuries, to return to the workforce. They are considered to
provide more useful data than can be obtained from clinical impression or self-report alone. Previously
however, there were limited data to support the psychometric properties of commonly used FCEs. We have
found the GAPP FCE to be safe, through the use of a prescribed pre-screening procedure, and through the
monitoring of biomechanisical, physiological and psychophysical parameters during the performance of tasks.
We found the results from the GAPP FCE to be reliable when silently observed by multiple therapists, that is,
the overall recommendations for return to work made by independent therapists had reliability ratings (ICC
[2,1]) of 0.73 and 0.75.
Expected future outcomes:
Since publication of key papers in peer reviewed journals in 2005, dialogue with other research groups has
begun, to enhance the science of FCEs. Our research team will continue to work on developing the FCE so it
can be available for day-to-day use in many settings around Australia. The team is meeting to plan the steps in
the commercialisation process over the coming months.
Name of contact:
Professor Jenny Strong
NHMRC Research Achievements - SUMMARY
Email/Phone no. of contact:
j.strong@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 142958
CIA Name: Prof Mark Forwood
Admin Inst: University of Queensland
Main RFCD: Orthopaedics
Total funding: $301,018
Start Year: 2001
End Year: 2003
Grant Type: NHMRC Project Grants
Title of research award:
Prostaglandin G/H synthase-2 (PGHS-2) is a key regulator of skeletal adaptation and remodellingProstaglandin
G/H synthase-2 (PGHS-2) is a key regulator of skeletal adaptation and remodelling
Lay Description (from application):
Knowledge of the biology underlying bone formation is important for developing novel approaches to
stimulate new bone formation in skeletal diseases associated with ageing or disability, or for maintenance of
new bone around orthopaedic or dental implants. The discovery that a prostaglandin enzyme (PGHS-2) is a key
factor in activity-related bone formation and normal bone turnover, as well as a pharmacological target for
reducing inflammation, has considerable clinical significance. Specific inhibition of PGHS-2 by recent antiinflammatory drugs avoids formation of gastric ulcers, but their influence on normal bone remodelling and
fracture repair is not known and must be investigated. Many such inhibitors are in advanced clinical trials, but
their effect on bone metabolism has not been published. This project is important because it employs novel
experimental models to advance our knowledge of prostaglandin biology in skeletal adaptation, and elucidates
important clinical consequences for specific inhibition of PGHS-2 in the skeleton. This project will investigate
the regulation of prostaglandin production by PGHS enzymes following mechanical loading in vivo. It will use
cell, molecular and histochemical techniques to determine if the genes that regulate the enzymes are influenced
by mechanical stimuli, and if they are dependent on other molecules, associated with structural proteins (stress
fibres) within the cell. It will investigate if inhibition of PGHS-2 by antiinflammatory drugs or stress-fibre
inhibitors, depresses normal bone turnover and healing responses. The outcome of these experiments could
indicate new approaches to stimulate bone formation, preserve bone mass, or minimise adverse skeletal effects
of anti-inflammatory treatments related to orthopaedic or dental procedures.
Research achievements (from final report):
The experiments showed that PGHS-2 (or COX-2) gene expression (normally related to inflammation) is
increased in bone tissue following loading. It also provided experimental evidence that PGHS-2 inhibition
reduces bone turnover which can prevent menopause related bone loss. This was shown to be related to
decreases in osteoclast surface and activity - the cells that remove bone. PGHS-2 inhibitors (anti-inflammatory
drugs) also slowed the remodelling and consolidation of woven bone on the periosteal surface following
loading. This would lead to increased healing time for fractures, but would not jeopardise the strength of those
healing fractures. The findings above suggest that there is a clinical implication for COX-2 inhibition in terms
of regulating bone turnover, but this has not yet been translated into a direct clinical outcome.
Expected future outcomes:
Evidence that new antinflammatory drugs not only reduce inflammation, but may have a role in managing and
regulating bone diseases associated with rapid bone loss, will be investigated. The role of COX-2 in bone
biology is being pursued in mice producing excess levels of this enzyme to study whether this exacerbates
conditions of bone loss or enhances adaptive mechanisms associated with loading
Name of contact:
Mark Forwood
Email/Phone no. of contact:
m.forwood@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 143021
CIA Name: Prof Justin Kenardy
Admin Inst: University of Queensland
Main RFCD: Mental Health
Total funding: $185,889
Start Year: 2001
End Year: 2003
Grant Type: NHMRC Project Grants
Title of research award:
A prospective study of traumatic stress in children involved in motor vehicle accidentsA prospective study of
traumatic stress in children involved in motor vehicle accidents
Lay Description (from application):
Motor vehicle accidents (MVAs) are relatively frequent major life trauma that represent significant life
threatening experiences. Not surprisingly evidence suggests that MVAs represent a frequent trigger for the
development of post traumatic stress disorder (PTSD), although studies have typically focussed upon adult
survivors. Local statistics indicate a significant proportion of children will experience a MVA of sufficient
severity to warrant attendance at hospital. This project is of significance because it will provide badly needed
information about the prevalence and course of emotional and behavioural problems in children following
exposure to a serious MVA. More broadly the study should provide valuable information on post-traumatic
stress responses in children. Furthermore, it will enable us to identify the factors that place children at
particular risk of developing psychological problems following a MVA. This will provide information to help
design of interventions to prevent the development of PTSD and other forms of psychopathology following
MVAs. Such data will also permit identification of those children who are at particular risk of psychological
morbidity after MVA trauma and for whom preventive interventions are most likely to be beneficial.
Research achievements (from final report):
This project investigated the prevalence of post traumatic stress reactions in children injured in accidents, with
follow-up of families occurring within two weeks after the child's accident, at one month after the accident and
again at six months after the child's accident. Children were aged 7 to 15 at the time of the accident. The
research employed measures of child functioning as well as parental functioning. The study found that although
a significant number of children suffered initial distress at two weeks after the accident, the majority of
children made a relatively good psychological recovery. However, children who suffered significant distress at
one month after the accident were likely to still suffer from post traumatic symptomatology at six months after
the accident. This indicates that early identification of children suffering significant psychological distress
allows for early treatment of children who are unlikely to recover without intervention.
Expected future outcomes:
The outcomes of this research will form the basis of development of an intervention program aiming to prevent
and/ or minimise development of post traumatic stress disorder and other psychological disorders in children
injured in accidents. The risk factors identified in the original study allow early identification of children at risk
for development of these disorders.
Name of contact:
A/Prof. Justin Kenardy
Email/Phone no. of contact:
jkenardy@somc.uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 143054
CIA Name: Prof John Mattick
Admin Inst: University of Queensland
Main RFCD: Medical Bacteriology
Total funding: $407,546
Start Year: 2001
End Year: 2003
Grant Type: NHMRC Project Grants
Title of research award:
Genetic dissection of the biogenesis and function of type IV fimbriae of Pseudomonas aeruginosaGenetic
dissection of the biogenesis and function of type IV fimbriae of Pseudomonas aeruginosa
Lay Description (from application):
Pseudomonas aeruginosa is a common bacterium which causes serious life-threatening infections of individuals
with cystic fibrosis, AIDS or who have suffered severe burns or are undergoing cancer chemotherapy. This
pathogen, and a number of other important infectious bacteria use surface filaments, called fimbriae, like
grappling hooks to attach to the cells of the body and to move across host tissues. These fimbriae are produced
in response to environmental conditions, and are assembled by a process that is also used in the export of toxins
and other pathogenic molecules. This project will characterise genes which specify and control this system, as
a means to design better treatments against such bacteria, many of which are resistant to antibiotic treatment.
Research achievements (from final report):
Twitching motility occurs in most if not all bacterial pathogens. It is mediated by surface filaments termed type
IV pili and is central to the infection process, as well as to protective immunity - strains with non-functional
pili are non-infectious and antibodies against type IV pili prevent disease. The model experimental organism
for this system is Pseudomonas aeruginosa, which is an important pathogen in its own right affecting
individuals with cystic fbrosis, burns, or who are suffering HIV-AIDS or undergoing cancer chemotherapy.
Other pathogens with type IV pili are those causing gonorrhea, menigitis, and conjunctivitis. During the course
of this project we discovered several new genes controlling twitching motility in Pseudomonas aeruginosa,
bringing the number of genes and proteins known to be involved to over 40. We also discovered that
extracellular DNA is required for biofilm formation, a process that is itself central to host colonization and
which involves twitching motility. This discovery was published in the leading journal Science with wide
accompanying publicity, and will open up new avenues for preventing biofilm formation and disease. We also
discovered that, contrary to previous reports, quorum sensing is not required for twitching motility but rather
that mutants in this system create regulatory imbalances that favour mutations in other regulators, including
those controlling twitching motility, with important ramifications for how mutational studies are interpreted in
bacteriology as a whole. We also characterized two regulatory systems which control twitching motility,
including a chemosensory system that includes the most complex signal transduction protein yet described in
any organism. Finally as acknowledged leaders in this field we were invited to publish a comprehensive review
on type IV pili and twitching motility by the Annual Review of Microbiology, which will stand for some time
as the definitive reference on the subject.
Expected future outcomes:
New protocols for screening for antibiotics that inhibit twitching motility. New approaches to the rational
design of antibiotics against twitching motility. New approaches to preventing bactertial biofilm formation.
Name of contact:
Professor John Mattick
Email/Phone no. of contact:
j.mattick@imb.uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 143061
Start Year: 2001
CIA Name: Prof Peter Koopman
End Year: 2003
Admin Inst: University of Queensland
Grant Type: NHMRC Project Grants
Main RFCD: Genetic Development (incl. Sex Determination)
Total funding: $468,564
Title of research award:
Transcriptional control of blood vessel development by Sox18Transcriptional control of blood vessel
development by Sox18
Lay Description (from application):
Blood vessels play an essential role in maintaining the supply of nutrients to every organ and tissue in the body.
Improper development of blood vessels in the embryo can compromise survival of the embryo, and defects in
the ability of blood vessels to grow, regenerate and adapt to change during adult life can be life-threatening.
The growth of new blood vessels (angiogenesis) is also an important factor in the ability of solid tumours to
grow during the progression of cancer. It is therefore of fundamental importance in the health sciences to gain
an understanding of how blood vessels form and regenerate. As a result of our collaborative research efforts,
we have discovered a gene, Sox18, that appears to regulate blood vessel development by controlling the
formation and/or behaviour of endothelial cells, which line the blood vessels and make them impermeable. Our
research so far indicates that MICE WITH DEFECTS IN SOX18 DIE FROM VASCULAR DEFECTS,
underlining the importance of this gene. THIS PROJECT IS CONCERNED WITH FINDING OUT HOW
SOX18 WORKS - exactly what goes wrong in mice lacking this gene, whether Sox18 can influence
endothelial cell behaviour in cell culture, how Sox18 comes to be active in endothelial cells, what genes are
switched on by Sox18, and what genes Sox18 co-operates with in its role in endothelial cells. The answers to
these questions will not only provide fundamental basic information about how blood vessels development is
controlled, but also sow the seeds for possible future therapies in which blood vessel development could be
stimulated (eg in wound healing) or suppressed (eg in tumour progression) through pharmaceutical
intervention.
Research achievements (from final report):
We are researching the genetic mechanisms by which blood vessels form - an issue of critical importance to
normal embryo development, physiological functioning and many diseases including cancer. We have
discovered one of the key genes in the process, a gene called Sox18. In this project we discovered a wealth of
information regarding what Sox18 does, how it achieves its roles in the cell, and how it contributes to
development, wound healing and cancer. Our data raise the exciting possibility that future therapies aimed at
speeding up or slowing down blood vessel development could be based on the Sox18 gene.
Expected future outcomes:
We are now exploring further the link between Sox18 and cancer, with a view to developing new therapies
involving inhibiting growth of blood vessels.
Name of contact:
Neville Young
Email/Phone no. of contact:
n.young@imb.uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 157085
CIA Name: Prof Paul Hodges
Admin Inst: University of Queensland
Main RFCD: Motor Control
Total funding: $168,958
Start Year: 2001
End Year: 2005
Grant Type: NHMRC Project Grants
Title of research award:
Physiology and pathophysiology of trunk control mechanismsPhysiology and pathophysiology of trunk control
mechanisms
Lay Description (from application):
The overall aim of this series of experiments is to understand how the spine is controlled and how this changes
in disease. Altered control has been identified in people with low back pain, yet we still know very little about
the normal mechanisms for protection and support of the spine. Back pain is a common affliction that affects
about 5% of Australians each year and is the most common and expensive work-related injury in western
society. An understanding of normal control and the mechanism of dysfunction is critical for identification of
risk factors and development of strategies for rehabilitation and prevention. The experiments are divided into
two series. The first series addresses normal spinal control. The questions to be asked deal with how the brain
copes with the challenge of using trunk muscles for breathing and spinal control at the same time, how the
activity of the trunk muscles is affected by input from sensory receptors in the joints, ligaments and muscles of
the spine, and whether intra-abdominal pressure can support the trunk. The second series deals with clinical
populations. The first aim is to identify whether people with respiratory diseases use trunk muscles for spinal
control and breathing at the same time. If they cannot, we predict that they will be more prone to low back
pain. We will test this in a large study of incidence of low back pain in people with and without respiratory
disease. The second study will investigate the pelvic floor muscles which are important for continence and
assist with spinal control. We will investigate whether people with incontinence have poor spinal control and
whether this leads to back pain. The final experiment will identify whether people with low back pain interpret
sensory information from the spine differently. By answering these questions we hope to intervene in the
enormous personal, social and economic consequences of LBP which affects between 60-90% of the
population at some stage in their life.
Research achievements (from final report):
This project involved a series of clinical and experimental studies to investigate the strategies used by the
nervous system to control the spine and changes that occur in pain and disease. The studies provide a range of
important outcomes that can guide the management and prevention of low back and pelvic pain. Key outcomes
include: , . Injury to a disc in the lumbar spine causes unexpectedly rapid atrophy of back muscles. This is
likely to compromise control of the spine. These data provide a physiological rationale for exercise in back
pain. This study was awarded the ISSLS prize, the premier international award for spine research. , . A novel
series of experiments studied the consequences of competition between the contribution of the spinal muscles
to control of movement and stability and the contribution of these muscles to respiration and continence. The
results show that increased demand for breathing and continence, due to disease or a function-specific
challenge (e.g. breathing increased carbon dioxide, increased bladder volume), is associated with compromised
control of the spine. This was linked to epidemiological data that showed an increased risk for development of
back pain in individuals with breathing difficulties and incontinence. , . Studies also show that low back pain,
when induced experimentally, leads to dramatic changes in coordination of spinal muscles. , The studies
provide evidence of factors that compromise control of the spine. These findings have led to changes in
evaluation and management of back pain. Ongoing work aims to assess the efficacy of these refined
interventions.
Expected future outcomes:
The studies completed in this program provide a basis for a range of strategies that have the potential to refine
the management and prevention of low back and pelvic pain. Future studies are required to determine the
magnitude of the clinical effect.
NHMRC Research Achievements - SUMMARY
Name of contact:
Paul Hodges
Email/Phone no. of contact:
p.hodges@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 157203
CIA Name: Prof Paul Hodges
Admin Inst: University of Queensland
Main RFCD: Not Allocated
Total funding: $484,676
Start Year: 2001
End Year: 2005
Grant Type: Established Career Fellowships
Title of research award:
Physiology and pathophysiology of trunk control mechanismsPhysiology and pathophysiology of trunk control
mechanisms
Lay Description (from application):
Not Available
Research achievements (from final report):
The work undertaken during the 5 years of the Research Fellowship involved investigation of the physiology
and pathophysiology of movement control in people with a range of conditions including low back pain,
respiratory disease and incontinence. Using physiological and epidemiological methods in human and animal
experiments the studies provide novel data of a range of factors that challenge the control of the trunk muscles,
and have led to the development of intervention strategies. Examples include: , . Animal experiments showed
that injury to an intervertebral disk leads to rapid atrophy of the deep back muscles. , . Evaluation of a large
population of Australian women showed that incontinence and breathing disorders are a risk factor for the
development of back pain. Other studies suggest that this may be due to competition between the contribution
of the trunk muscles to spinal control, continence and breathing. , . Studies show that pain and fear of pain lead
to complex changes in the control of the trunk muscles. This suggests that patients who are fearful of injury
control movement as if they have pain. These studies point to changes in control of the muscles, rather than
strength and endurance. , . Similar changes in muscle control were also identified in people with neck pain,
knee pain and shoulder pain. , . Clinical trials of exercise strategies based on these studies provided evidence of
clinical efficacy in people with back, neck and knee pain. Other studies showed that the improvement in
symptoms is associated with improvements in muscle control.
Expected future outcomes:
The completed studies have provided evidence of a range of factors that are candidates as risk factors for the
development and recurrence of low back pain. Current and future work aims to determine whether clinical
interventions can change these factors and improve the long term prognosis for those at risk for back pain.
Name of contact:
Paul Hodges
Email/Phone no. of contact:
p.hodges@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 210146
CIA Name: Dr James St John
Admin Inst: University of Queensland
Main RFCD: Sensory Systems
Total funding: $256,320
Start Year: 2002
End Year: 2004
Grant Type: NHMRC Project Grants
Title of research award:
Defining the role of EphA5 in olfactory axon growth, guidance and fasciculationDefining the role of EphA5 in
olfactory axon growth, guidance and fasciculation
Lay Description (from application):
The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life
and it can regenerate even after injury. It therefore provides an excellent model for examining the growth,
development and maintenance of nerve cells. This project will examine the effects on the organisation of the
olfactory system when some guidance signals are altered. Information we obtain about how this system
develops and regenerates may be useful in treating brain disorders and spinal injuries In the current project we
will examine the effects of specific nerve cell guidance molecules by generating transgenic mice that produce
these molecules only in the olfactory system. We can then determine what changes occur to the nerve cells
when these extra molecules are produced. In addition, we will also examine the behaviour of live cells as they
are growing. In the past all attempts to understand how nerve cell connections are formed in the olfactory
system have used dead tissue that has been permanently preserved. In this project we have the unique
opportunity to visualise living nerve cells to enable us to determine how the cells react to the guidance signals.
The advantage of this approach is that it allows us to identify important interactions as they occur, rather than
attempting to decipher them after they have occurred. An analogy would be watching a football game live and
observing how goals were scored and appreciating the performance of individual players versus trying to guess
from the final score how the game was played and who the key performers were. The results of these
experiments will provide important information on the regeneration of olfactory nerve cells, as well as on the
initial growth and targeting of these nerve cells.
Research achievements (from final report):
The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life
and it can regenerate even after injury. It therefore provides an excellent model for examining the growth,
development and maintenance of nerve cells. This project has examined the effects on the organisation of the
olfactory system when some guidance signals are altered. Nerve cells find their appropriate target by following
a combination of guidance cues. However different guidance molecules are likely to present in the young
animal compared to the adult and therefore regeneration may be different in animals of different ages. We have
examined how nerve cells find their targets following widespread regeneration in the adult and found that
targeting is often inaccurate with nerve cells terminating in numerous inappropriate sites. These results support
the notion that the coordinated expression of a suite of guidance cues is required for correct nerve cell targeting
during development and during regeneration in the adult. Our results have provided an excellent understanding
of how the sense of smell develops and regenerates and these results may be useful in treating brain disorders
and spinal injuries.
Expected future outcomes:
Design of drug and cell-based therapies for brain and spinal regeneration
Name of contact:
James St John
Email/Phone no. of contact:
james.stjohn@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 210347
Start Year: 2002
CIA Name: Dr Tamara Ownsworth
End Year: 2006
Admin Inst: University of Queensland
Grant Type: Early Career Fellowships (Australia)
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $214,230
Title of research award:
Impaired self-awareness & employment outcome following acquired brain injury: Evaluation of an
employment rehabilitationImpaired self-awareness & employment outcome following acquired brain injury:
Evaluation of an employment rehabilitation
Lay Description (from application):
Not Available
Research achievements (from final report):
This 4 year project investigated the relationship between metacognitive skills (i.e., self-awareness and selfregulation) and functional outcomes following acquired brain injury (ABI). In the first stage of the project 86
individuals with ABI were involved in a 12-month longitudinal study of return to work and other psychosocial
outcomes. In the second stage of the project a series of rehabilitation interventions were evaluated involving
approximately 38 individuals, and included a case series (n=3), single case experimental designs (n=2) and a
randomised controlled trial (n=33)., The key findings of the project were as follows:, - Impaired metacognitive
skills were associated with poor problem solving and error self-regulation;, - Impaired metacognitive skills and
depression predicted employment outcome and independent living skills;, - Improvement in self-awareness
over time was associated with obtaining employment;, - Individuals with ABI were distinguished into 4
clusters according to awareness. These include: (1) poor self-awareness due to executive dysfunction, (2) high
defensiveness and low symptom reporting, (3) high symptom reporting and low defensiveness and (4) good
self-awareness. These clusters predicted emotional well-being and psychosocial outcomes., - Metacognitive
skills can be enhanced through group rehabilitation and individual occupation-based programs in the
community. This training leads to significant clinical gains in goal attainment, emotinal well-being and
psychosocial adjustment., , From a clinical perspective, the findings highlighted the importance and
effectiveness of training metacognitive skills during rehabilitation to enhance return-to-work outcomes,
independent living skills and interpersonal relationships. Our evidence-based practice guidelines for
rehabilitation are published in leading journals such as Clinical Psychology Review, Journal of the
International Neuropsychological Society, and Neuropsychological Rehabilitation.
Expected future outcomes:
Various publications are in press and continue to be submitted as a result of the project. The randomised
controlled trial which commenced during the NHMRC project is near completion (funded by CONROD) and
will be submitted for publication. International collaborative research, involving the application of the research
methodology to other clinical populations, is ongoing.
Name of contact:
Dr Tamara Ownsworth
Email/Phone no. of contact:
t.ownsworth@griffith.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 252771
Start Year: 2003
CIA Name: Prof Gwendolen Jull
End Year: 2005
Admin Inst: University of Queensland
Grant Type: NHMRC Project Grants
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $264,750
Title of research award:
Physiological mechanisms of efficacy of cervical flexor muscle retrainingPhysiological mechanisms of
efficacy of cervical flexor muscle retraining
Lay Description (from application):
Neck pain is a significant problem in society and its frequency is beginning to match the proportions of back
pain, probably reflecting our increasingly sedentary lifestyles. Several problems have been identified in the
muscle system in persons who suffer from neck pain. Therapeutic exercise has been found to have benefit in
preventing and relieving pain and improving the neck function. Currently there are several, quite different
methods of exercise and there is controversy regarding how therapeutic exercise works. It has been argued that
parameters such as changes in muscle strength, endurance, joint position sense or muscle coordination may be
responsible for the clinical efficacy. It is difficult to disentangle the effective component of exercise strategies
and thus prescribe the most effective exercise strategies. This series of experiments will evaluate the
physiological factors that change with a specific exercise intervention and to compare different exercise
modalities in order to identify the most effective means to induce these changes. Cervical muscle training,
using a proven exercise intervention strategy for chronic neck pain and headache, has been chosen as the model
to investigate these questions. This exercise strategy has been chosen not only because it has been shown to be
effective, but also because it does not conform to contemporary rationales for strength or endurance training.
Thus while effective in relieving pain, it is unlikely to produce changes in these parameters. Thus other
mechanisms are likely to be responsible for the clinical change. This research stands to make a significant
contribution to exercise therapeutics by identifying the effective components of different exercise methods and
investigating the pain relieving effects of the specific exercise. This knowledge will lead to the construction of
a research based exercise program for neck pain patients, rather than have the current situation of often
arbitrary choice of exercise.
Research achievements (from final report):
Neck pain is a significant problem in society and its frequency is beginning to match the proportions of low
back pain. Changes in neck muscle function have been identified in people with neck pain and therapeutic
exercise programs designed to address these deficits, have demonstrated efficacy in relieving neck pain.
However, several, quite different methods of exercise have been proposed and there is controversy regarding
optimal exercise selection and how exercise achieves pain relief. It has been argued variously that parameters
such as changes in neck muscle strength, endurance, joint position sense or muscle coordination may be
responsible for the clinical efficacy. , A series of experiments was undertaken to evaluate the effect of various
exercise regimes on physiological measures of neck muscle function which are known to be impaired in people
with neck pain. The results indicated that specificity in training is required to most effectively change neck
muscle impairment. This knowledge has translated to the construction of a research based, progressive exercise
program for neck pain patients, rather than the current situation of an arbitrary choice of exercise. The efficacy
of this exercise approach is currently being tested in a randomised clinical trial for neck pain following a
whiplash injury.
Expected future outcomes:
The results of the research will guide further development of specific therapeutic exercise interventions for the
management and prevention of neck pain, based scientifically on the physiological responses to training.
Name of contact:
Gwendolen Jull
Email/Phone no. of contact:
NHMRC Research Achievements - SUMMARY
g.jull@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 252829
CIA Name: Prof Brian Key
Admin Inst: University of Queensland
Main RFCD: Sensory Systems
Total funding: $440,250
Start Year: 2003
End Year: 2005
Grant Type: NHMRC Project Grants
Title of research award:
A molecular approach to constructing the olfactory systemA molecular approach to constructing the olfactory
system
Lay Description (from application):
The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life
and it can regenerate even after injury. It therefore provides an excellent model for examining the growth,
development and maintenance of nerve cells. This project will examine the effects on the organisation of the
olfactory system when some guidance signals are altered. Information we obtain about how this system
develops and regenerates may be useful in treating brain disorders and spinal injuries In the current project we
will examine the effects of specific nerve cell guidance molecules by generating transgenic mice that produce
these molecules only in the olfactory system. We can then determine what changes occur to the nerve cells
when these extra molecules are produced. The results of these experiments will provide important information
on the the initial growth and targeting of these nerve cells which may have implications for regeneration of
these as well as other nerve cells.
Research achievements (from final report):
This project has led to a better understanding about how one of the most regenerative regions of the nervous
system forms during development and matures into old age. The region of the nervous system associated with
smell is called the olfactory system. It is unique because its nerve cells are continually dying throughout life
and being replenished by progrenitor cells that mature into new nerve cells. In contrast, in other regions of the
nervous system nerve cells typically die with age and are never replenished. This makes the olfactory system
interesting for regneratine purposes. In this project we have begun to understand how the olfactory nerve cells
are able to conitunally grow throughout life. It is hoped that this infromation will lead to the design of
therapeutic approaches ot injury in the nervous system.
Expected future outcomes:
The long term outcomes of this work is the developemnt of strategies to assist in repairing nervous systems
damaged by either physical insult or due to disease and pathologies. An important future outcome is to induce
growth and regeneration in other regions of the nervous system at levels comparable to that observed in the
olfactory system.
Name of contact:
Brian Key
Email/Phone no. of contact:
brian.key@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 276415
CIA Name: A/Pr Edith Gardiner
Admin Inst: University of Queensland
Main RFCD: Endocrinology
Total funding: $496,500
Start Year: 2004
End Year: 2006
Grant Type: NHMRC Project Grants
Title of research award:
Anabolic Bone Gene PathwaysAnabolic Bone Gene Pathways
Lay Description (from application):
Osteoporosis is a major health burden resulting from bone fractures in older men and women due to
progressive loss of bone and weakening of the skeleton. Although there are currently therapies to reduce bone
loss, no current treatment effectively reconstructs lost bone. In this project, which is designed to identify new
genes that may in the future be targeted by drugs to reverse osteoporosis, we have identified specific sets of
genes that appear to work together to increase bone formation. This proposal is aimed at characterising these
genes and the ways in which they work to determine whether they may be good targets for new osteoporosis
treatments. We will examine the patterns of these genes in bone. We will also use cell cultures in which bone
forming cells develop and function, to determine when the genes are expressed and how they function. We will
test the ability of the candidate genes to cause an increase in the amount of bone forming activity in these cell
cultures. An increase in bone formation may be caused by an increase in the number bone-forming cells, an
increase in the activity of the cells, a decrease in cell death, or a combination of these changes. Each possibility
will be tested. This research is important because of the need for new osteoporosis therapies to repair
weakened bones. The knowledge resulting from this proposal has the potential to provide an important
contribution to skeletal health and thus aged health worldwide.
Research achievements (from final report):
Osteoporosis is a condition in which bones are fragile, at least in part because of a decrease in bone mass. In
osteoporosis research, the Wnt regulatory pathway is being studied because it can increase bone mass by
increasing the activity of osteoblasts, which are the bone forming cells. How the Wnt pathway stimulates
osteoblast activity is not well understood, however, and in this project we have unexpectedly discovered that
under some circumstances, Wnt pathway activation can inhibit the bone forming activity of osteoblasts. In
experiments designed to explain how this unusual observation could occur, we have demonstrated that Wnt can
alter the expression of key genes that control the development and maturation of osteoblasts. We have also
discovered a novel mechanism of interaction between the Wnt pathway and another major regulator of
osteoblasts, the vitamin D response pathway. The knowledge gained in these experiments is important because
any future osteoporosis therapies based on Wnt pathway activation must take into account the potential
negative as well as positive effects of such interventions. Better understanding of the range of consequences of
Wnt activation including the effects on the osteoblastic vitamin D response will aid in the development of
effective strategies for both Wnt and vitamin D based therapies.
Expected future outcomes:
Future studies will determine why the negative effects of Wnt activation on bone formation occur under some
circumstances but not others.
Name of contact:
Edith Gardiner
Email/Phone no. of contact:
e.gardiner2@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 301026
CIA Name: Prof Brian Key
Admin Inst: University of Queensland
Main RFCD: Cellular Nervous System
Total funding: $447,750
Start Year: 2004
End Year: 2006
Grant Type: NHMRC Project Grants
Title of research award:
Molecular and cellular mechanisms of axon guidance in the vertebrate nervous systemMolecular and cellular
mechanisms of axon guidance in the vertebrate nervous system
Lay Description (from application):
There are, at least, two major obstacles that have to be overcome in the design of therapies to assist the repair
of injured brain tissue. First, the nerve cells that are damaged have to be encouraged to regrow - typically this
regrowth is inhibited in the brain; and second, this regrowth has to be directed so that the correct connections
are re-established. This project will begin to unravel some of the mechanisms that nerve cells use to wire up
together during development. This information can be used to assist in trying to modulate and facilitate
directed regrowth following injury.
Research achievements (from final report):
There are, at least, two major obstacles that have to be overcome in the design of therapies to asssist the repair
of injured brain tissue. First, the nerve cells that are damaged have to be encouraged to regrow - typically this
regrowth is inhibited in the brain; and second, this regrowth has to be directed so that the correct connections
are re-established. This project has begun to unravel some of the mechanisms that nerve cells use to wire up
together during development. This information will be used to assist in trying to modulate and facilitate
directed regrowth following injury. We have been the first to characterise the interaction between three
molecules during the period in early development when a template of the nerve connections is being formed.
This work has contributed significantly to our understanding of how genes control nerve fiber growth.
Expected future outcomes:
This work will lead to a better understanding of how molecules regualte the growht of nerve fibres in the brain.
It is expected that techniques will be developed that will allow these molecules to be regualted both in time and
space so as to facilitate the repair of damaged tissue in the brain following either direct injury or disease states.
Name of contact:
Brian Key
Email/Phone no. of contact:
brian.key@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 301037
Start Year: 2004
CIA Name: Prof Bill (Guglielmo) Vicenzino
End Year: 2006
Admin Inst: University of Queensland
Grant Type: NHMRC Project Grants
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $192,625
Title of research award:
Foot orthotics in the treatment of patellofemoral pain syndrome: A randomised control trial in primary
careFoot orthotics in the treatment of patellofemoral pain syndrome: A randomised control trial in primary care
Lay Description (from application):
Musculoskeletal conditions account for the third leading cause of health systems expenditure in Australia.
Patellofemoral pain syndrome or pain about the knee cap is such a condition and is often treated in primary
care. Both the individual and community are affected by this condition with an estimated 1 in 4 suffers still
having problems and pain up to 20 years after first being afflicted. Importantly it interferes with activities such
as walking, jogging, gym classes and aerobics, which are often prescribed to prevent serious conditions of the
heart, diabetes and obesity. Hence it negatively impacts on the health and well being of our nation. Two
popular treatment options that are commonly prescribed for the management of patellofemoral pain syndrome
are physiotherapy and foot orthotics. To date there is some evidence supporting physiotherapy, especially
current best practice methods such as a combined program of therapeutic exercise, manual therapy and kneecap
taping. There is a lack of evidence for the use of orthotics in treating patellofemoral pain syndrome. This
project will conduct a randomised clinical trial to evaluate the relative benefits of orthotics as the sole treatment
of patellofemoral pain syndrome and also when combined with physiotherapy. Factors associated with
predicting the results of orthotic therapy will be studied to see if there are any tests that a health care
practitioner can perform to provide information early on in a consultation regarding possible treatment
outcomes. A cost-benefit analysis will also be conducted to calculate the relative economic merits of the
treatments. A tangible outcome of this project will be the development of clinical guidelines for the most
effective method of treating patellofemoral pain syndrome in primary health care.
Research achievements (from final report):
Patellofemoral pain syndrome (pain at the front of the knee) is a common musculoskeletal condition that
substantially interferes with physical activity (e.g., walking on flat, stairs or hills; jogging; cycling) and may
last for many years. This project addressed the issue of timely managing this condition by systematically
reviewing reports of other up to date research as well as conducting the first full scale clinical trial of the role
of physical treatments, such as, foot orthoses and physiotherapy. Previous research identified in the systematic
reviews indicated that there might be a beneficial effect of foot orthoses, but that the findings of those
preliminary studies were not conclusive. To the contrary physiotherapy in the form of exercises, manual
therapy and taping was beneficial. Our clinical trial tracked 179 patients over 12 months and found a poorer
prognosis for those who had severe pain for longer and had lower functional levels, irrespective of their age,
gender or general body shape. This trial also evaluated the clinical benefits of treatment with pre-formed foot
orthoses in 179 patients and found that foot orthoses were more effective than flat shoe inserts in the shortterm, but that they were not substantially different to physiotherapy (or combined orthoses and physiotherapy)
over 12 months. Interestingly, the foot orthoses were more almost twice as effective in people with mobile feet
who were relatively older, shorter and had less severe pain. In summary, it would appear that foot orthoses
might be used to hasten recovery in patellofemoral pain syndrome.
Expected future outcomes:
The clinical trial was published in a high impact medical journal and has attracted attention (e.g., reprinted in
British Journal of Sports Medicine, invitation to speak at national and international conferences), which sets a
platform for uptake of this research in clinic and research - with downstream improved health of active young
people, thereby preventing complications of inactivity.
Name of contact:
Bill Vicenzino
NHMRC Research Achievements - SUMMARY
Email/Phone no. of contact:
b.vicenzino@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 301099
CIA Name: A/Pr Helen Cooper
Admin Inst: University of Queensland
Main RFCD: Cellular Nervous System
Total funding: $432,750
Start Year: 2004
End Year: 2006
Grant Type: NHMRC Project Grants
Title of research award:
Dissecting the molecular mechanisms driving cell migration during neurulation triggered by the netrin receptor,
neogeninDissecting the molecular mechanisms driving cell migration during neurulation triggered by the netrin
receptor, neogenin
Lay Description (from application):
In humans, abnormalities in brain and spinal cord formation during early embryogenesis result in congenital
syndromes such as spina bifida and anencephaly. These defects occur at a rate of 1/1000 pregnancies and are
therefore a major contributor to pre- and perinatal deaths. In the early embryo, the brain and spinal cord begin
as a hollow tube of cells (the neural tube) that subsequently expands into the complex structures seen at birth. It
is known that the neural tube is formed by a complex process in which early neural cells migrate toward the
midline of the embryo and subsequently coalesce. This project seeks to determine the function of one
molecular signaling pathway (the neogenin pathway) that has been implicated in driving these cell migration
events. We will initially use the frog, Xenopus laevis, as our embryonic model since the developmental
processes that form the Xenopus neural tube closely parallel those ocurring in the human embryo. This model
will allow us to identify the molecules in the neogenin signaling pathway. We will also create mice that carry a
mutation in the neogenin gene so that we can study neogenin function in the mammal. We anticipate that these
studies will provide important insights into the development of the central nervous system and also into the
aberrant molecular processes underlying neural tube defects in man.
Research achievements (from final report):
Cell migration is one of the principal events in laying out the architectural plan of the central nervous system
during embryogenesis. The netrins and their receptor, Neogenin, are now emerging as a major guidance system
driving neural migration the embryo. Our recent studies have used Xenopus (frog) embryos as our
developmental model to demonstrate that Neogenin is a key receptor responsible for the correct formation of
the neural tube, the earliest identifiable brain structure. We have shown that loss of Neogenin impairs neural
migration resulting in significant morphological abnormalities in the neural tube. Furthermore, these
abnormalities eventually suppresses neuron production throughout the developing brain. Similar abnormalities
are seen during human neural tube formation leading to anencephaly and spina bifida. Such failures in neural
tube development occur in 1/1000 human pregnancies. Therefore, understanding the role of Neogenin in neural
tube development is providing new insights into prevalent human central nervous system developmental
abnormalities.
Expected future outcomes:
We have identified a possible novel molecular drug target for the prevention of neural tube defects in the
embryo. We are now exploring this idea further.
Name of contact:
Helen Cooper
Email/Phone no. of contact:
h.cooper@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 301103
Start Year: 2004
CIA Name: Prof Justin Kenardy
End Year: 2006
Admin Inst: University of Queensland
Grant Type: NHMRC Project Grants
Main RFCD: Health, Clinical and Counselling Psychology
Total funding: $482,250
Title of research award:
Cognitive impairments and post traumatic stress symptoms in children with traumatic brain injury: A
longitudinal studyCognitive impairments and post traumatic stress symptoms in children with traumatic brain
injury: A longitudinal study
Lay Description (from application):
Traumatic brain injury in children is common with more than 2000 new cases a year in Queensland and
Victoria alone. Many children who experience a brain injury go on to have long-term difficulties such as
significant educational and social problems. Post-traumatic stress occurs in children following traumatic
physical injury. However it is not clear to what extent this is so for children who have received a traumatic
brain injury. Furthermore, when there is a traumatic brain injury and traumatic stress, it is not clear how these
interact, how they influence long-term outcomes, and what factors such as pre-injury functioning and family
support and distress mediate outcomes. These issues are very important since effective rehabilitation of
children following traumatic brain injury is essential to maximise long-term functioning and minimise
disability. To be effective, rehabilitation must be guided by the knowledge about key factors that determine the
recovery process. This study aims to provide answers to these questions by following two cohorts of children
(aged 6-14) over 18 months after receiving a traumatic brain injury. In total 240 children will be recruited from
Brisbane and Melbourne hospitals. They will be assessed at three, six, twelve and eighteen months post-injury
using measures of cognitive, psychological and social functioning. Information on parent distress and
behaviours will also be obtained. The information obtained will provide the basis for the development of a
specific rehabilitation strategy for children with traumatic brain injury, including information on strategies to
help prevent any confounding impact of post-traumatic stress on recovery.
Research achievements (from final report):
The primary aim of this research was to investigate the psychological and cognitive sequelae of traumatic brain
injury (TBI) in children to examine the relationship between cognitive impairment and post-traumatic stress,
adjustment to injury, and the long-term impact on recovery. This study aims to describe the changing
relationships among key factors predicting outcome from childhood TBI (injury factors, pre-morbid child
characteristics, and family factors) up to 18 months post-injury. The recruitment of children with TBI was
completed at the end of 2006. During 2007 the first four assessment time points (pre-injury, three, six, and
twelve months) were completed and we are in the final stages of completing the eighteen month assessments.
This study is the largest head injury study with children in the world examining both cognitive and emotional
outcomes. To date, five papers have been presented at both national and international conferences. Two of the
conference presentations are being developed into papers for submission to peer-reviewed journals. The results
indicate a) children's pre-injury behaviour does not appear to influence the severity of children's TBI, b) the
psychological responses of children following TBI are better assessed with clinical interviews (CAPS-CA) in
comparison to self report measures (TSCC), c) among children with TBI executive functioning deficits include
speed of information processing and high-order cognitive flexibility, but no apparent deficits in goal setting or
reasoning, and, d) parental distress is associated with the severity of children's TBI and children's psychological
reactions but not their neuropsychological outcomes.
Expected future outcomes:
Final assessments (18-months) will be completed by end of 2008. The next stage of data analysis is to examine
post traumatic stress symptoms over time, the relationship between PTSD and cognitive and behavioural
outcomes, and PTSD and TBI severity, and to explore theoretical issues such as the diagnosis of PTSD in
children with TBI.
Name of contact:
NHMRC Research Achievements - SUMMARY
Professor Justin Kenardy
Email/Phone no. of contact:
j.kenardy@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 301137
Start Year: 2004
CIA Name: Prof Jennifer Stow
End Year: 2006
Admin Inst: University of Queensland
Grant Type: NHMRC Project Grants
Main RFCD: Protein Targeting and Signal Transduction
Total funding: $470,750
Title of research award:
LPS-regulated SNAREs and control of cytokine secretion in macrophages.LPS-regulated SNAREs and control
of cytokine secretion in macrophages.
Lay Description (from application):
TNF(tumour necrosis factor alpha) is a potent proinflammatory cytokine secreted by immune activated
macrophages. TNF has essential roles in host defense, tumour killing and energy metabolism. Excessive
secretion of TNF in acute and chronic inflammatory conditions, such as septic shock, Crohn s disease,
rheumatoid arthritis and in cancer has many severe, even fatal, consequences. Improved anti-TNF therapeutics
are needed for clinical management in all of these conditions. Our studies are focused on investigating how
macrophages synthesize and secrete TNF, with the ultimate goal of characterizing the molecules and vesicles in
the TNF secretory pathway. Our recent findings show the expression of SNARE proteins, part of the vesicle
docking and fusion machinery, is regulated in concert with cytokine secretion and other trafficking changes in
activated macrophages. We identified the proteins Syntaxin4, Munc-18c and SNAP-23 as the specific tSNARE complex that regulates TNF delivery to the cell surface. In the proposed studies we will investigate
how SNAREs are regulated during macrophage activation by studying their gene expression and protein
modifications. We have developed a single-cell assay to measure TNF trafficking in macrophages; this allows
the identification of molecules with roles in TNF secretion and it will be used in a series of experiments to
identify the specific v-SNARE proteins that partner the t-SNARE for TNF delivery. Finally we will use live
cell imaging to investigate how and where TNF is delivered to the macrophage cell surface and membrane
fractionation to examine a role for membrane microdomains in organizing SNARE-mediated TNF secretion.
Manipulation of SNAREs, using data generated by these studies, holds potential for the development of new
anti-TNF therapies.
Research achievements (from final report):
We have discovered new and unexpected cellular pathways that lead to the releae of cytokines or chemical
messengers from immune cells. These cytokines have necessary roles in inflammation and describing their
pathways for release generates a new level of understanding in this area. However the excess secretion of these
cytokines, TNF and IL-6, causes the chronic symptoms of inflammatory dieases like IBD and arthritis. Our
findngs identify, for the first time, molecules important for cytokine secretion that can potentiallly be targeted
by drugs for alternative and improved approaches to treating inflammation.
Expected future outcomes:
Our findings uncover potentially drug targets and strategies for blocking TNF secretion that could lead, in the
future, to new medicines for inflammatory disease.
Name of contact:
Jennifer Stow
Email/Phone no. of contact:
j.stow@imb.uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 301143
CIA Name: Prof Mark Forwood
Admin Inst: University of Queensland
Main RFCD: Endocrinology
Total funding: $440,750
Start Year: 2004
End Year: 2006
Grant Type: NHMRC Project Grants
Title of research award:
Investigation Of COX-2 Regulation Of Bone Turnover And Mechanically Induced Bone Formation By Genetic
overexpression.Investigation Of COX-2 Regulation Of Bone Turnover And Mechanically Induced Bone
Formation By Genetic overexpression.
Lay Description (from application):
This project is important because it uses novel experimental models to advance our knowledge of prostaglandin
biology in normal and pathological bone remodelling, and the response of the skeleton to increased physical
activity. We expect that a genetic modification in mice to increase the normal production of key prostaglandin
enzymes, cyclooxygenase-2 (COX-2), in bone cells will increase the number of cells that remove bone
(osteoclasts), and increase bone loss and the rate of bone turnover when compared to normal mice. We believe
this will occur via the effect of prostaglandins on expression of genes that control osteoclast formation. This
will be tested by examining the structure of the skeleton, and the expression of certain genes, in transgenic
mice at different ages from 2-8 months. These effects may be exacerbated in conditions of increased bone
turnover, such as postmenopausal bone loss. This will be tested by examining the bone structure and gene
expression in adult mice following removal of their ovaries. Due to the role of COX-2 in adaptation of bone to
mechanical loading, we also expect the load-bearing skeleton to be more sensitive to increased weight-bearing
activity. We will investigate this hypothesis by applying mechanical loads to the tibiae of mice in a controlled
manner and then analysing the bone structure. Knowledge of specific pathways by which bone formation can
be stimulated is important for developing novel approaches to induction and augmentation of osteogenesis in
skeletal diseases associated with ageing or disability, or for maintenance of new bone around implants. The
discovery that COX-2 is a key enzyme in mechanotransduction and osteoclastogenesis in bone, and a
pharmacological target for modulating inflammation, has considerable clinical significance. Exploiting this
knowledge requires precise knowledge of the role of this enzyme in bone remodelling and adaptation and our
experiments will contribute significantly to that knowledge
Research achievements (from final report):
This project used novel experimental models to advance our knowledge of prostaglandin biology in bone
health and disease. We used a genetic modification in mice that allowed us to increase the normal production
of prostaglandins in bone cells, alone. This was done by increasing the synthesis of an important enzyme in
bone resorbing cells called osteoclasts. The enzyme, cyclooxygenase-2 (COX-2) is normally found during
inflammation, but is also crucial for bone cell function. We observed that osteoclasts from these mice did
indeed express high levels of COX-2 when cultured in vitro. Importantly, using micro-computed tomography,
preliminary analysis of bone architecture of these mice revealed an osteoporotic phenotype compared to control
mice, suggesting the importance of this enzyme in such diseases. We believe this is mediated via the effect of
activated osteoclasts to increase bone turnover. This is now being tested. Generated in this project, COX-2
over-expressing mouse models could also be extremely valuable for evaluation of the in vivo effects and
efficacy of new, as well as existing, inhibitors of COX-2 activity. It is also possible that overexpression of
COX-2 in either or both cell types of bone can become a useful model(s) of disorders of bone turnover and
remodelling, e.g. osteoporosis.
Expected future outcomes:
We will use these mice to test the physiological role of COX-2 in the skeleton in these conditions where it is
being overexpressed. These experiments will examine the response of bone to mechanical loading, the loss of
bone following ovariectomy, and the role of COX-2 during fracture healing.
Name of contact:
Mark Forwood
NHMRC Research Achievements - SUMMARY
Email/Phone no. of contact:
m.forwood@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 301239
Start Year: 2004
CIA Name: Prof Gwendolen Jull
End Year: 2004
Admin Inst: University of Queensland
Grant Type: NHMRC Development Grants
Main RFCD: Therapies and Therapeutic Technology
Total funding: $110,633
Title of research award:
Cranio-Cervical Dynamometry in the Rehabilitation of Neck PainCranio-Cervical Dynamometry in the
Rehabilitation of Neck Pain
Lay Description (from application):
Research has demonstrated that exercising particular neck muscles in a specific manner is effective in reducing
painful neck symptoms. A device has been developed to quantify the performance of specific neck muscles,
permitting more precise rehabilitative exercise, tailored to an individual’s abilities and needs. The effectiveness
of this device in the rehabilitation of chronic neck pain will be tested in a clinical trial against other commonly
used forms of neck exercise.
Research achievements (from final report):
Neck pain is a common and costly problem in the community. Training of neck muscles has been shown to be
effective in reducing neck pain and disability. This study compared a new tecnology for rehabilitating the
muscles of the neck to other commonly used methods in clinical practice. Results have shown the new
technology was as effective as other commonly used methods of rehabilitation in reducing painful symptoms,
as well as demonstrating some superior results in neck muscle performance gains compared to the other
methods. The new technology was also adaptable for use in home setting, which has increased its commercial
potential.
Expected future outcomes:
The Neckmetrix technology has undergone further development to refine the commercial attractiveness of the
device. Negotiations with potential licencees are in progress. Further clinical trials are planned.
Name of contact:
Dr Shaun O'leary
Email/Phone no. of contact:
s.oleary@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 351408
Start Year: 2005
CIA Name: Prof Gwendolen Jull
End Year: 2007
Admin Inst: University of Queensland
Grant Type: NHMRC Project Grants
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $382,550
Title of research award:
Effective management of acute whiplash injuries requires a pragmatic approach: An RCT with stratified
treatmentsEffective management of acute whiplash injuries requires a pragmatic approach: An RCT with
stratified treatments
Lay Description (from application):
Whiplash injuries from a motor vehicle crash continue to incur substantial personal and financial costs to the
community and the insurance industry. The current approaches to an acute whiplash injury in Australia and
internationally have failed to lessen the rate of how many people develop chronic neck pain. Between 40 and
60% still have pain 6 months after injury. Motor Accident Insurance Commission (Qld) figures indicate that
20% of patients with chronic whiplash account for 60% of the costs. Transition from an acute to a chronic
condition must be prevented. A new direction in management in the acute stage is urgently required as once the
pain has become chronic, it is difficult to help. This research will conduct a novel randomised controlled trial
for acute whiplash. It will test individually prescribed multi-professional management against usual care with
the aim to lessen the numbers who go on to develop chronic pain. It will be the first clinical trial that
acknowledges from the outset that the whiplash injuries and affects people in different ways. Our previous
research with acute whiplash patients has documented the variations in presentation from physical,
physiological and psychological perspectives. In this trial, management will be prescribed as directed by
measurable pain, muscle and psychological impairments in the individual, rather than regard all patients as the
same as in other trials. This trial will offer individualised treatments; medical, physiotherapy and/or
psychological using an empirically derived treatment algorithm. Cost-effectiveness of the program will be
evaluated against that incurred during usual care. It is predicted that early multi-professional management will
be less expensive in the long term than existing approaches. This RCT stands to extend knowledge in the
management of whiplash associated disorders (WAD).
Research achievements (from final report):
The presentations of persons who suffer an acute whiplash injury from a motor vehicle crash vary
significantly,from minor neck pain only to severe pain which can be accompanied by considerable distress and
post-traumatic stress. Symptoms may persist for many years. Currently guidelines for management of acute
whiplash are general and focus broadly on activity and exercise, without considering variability in presentation.
This clinical trial examined whether a multiprofessional approach (medical, physiotherapy and/or health
psychology) provided to the particiant as indicated by their individual presenting complaints would be better
than current usual care in alleviating the condition and preventing ongoing symptoms. The costs of care were
also investigated. The results of the trial indicated that the pragmatic multiprofessional approach overall
offered no significant benefits over usual care in the short or long term, although there were indications that
persons who reported high levels of pain and disability following the whiplash injury benefited more with
multiprofessional managment. Multiprofessional management cannot be justified for the acute whiplash state
for the majority of patients.
Expected future outcomes:
Prospective studies have shown that high inital pain and disability is one of the strongest prognostic indicators
for poor outcome following injury. The results of this clinical trial would suggest that this group be the target
of future research into multiprofessional management methods.
Name of contact:
Professor Gwendolen Jull
Email/Phone no. of contact:
NHMRC Research Achievements - SUMMARY
g.jull@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 351479
CIA Name: Prof Andrew Boyd
Admin Inst: University of Queensland
Main RFCD: Central Nervous System
Total funding: $491,000
Start Year: 2005
End Year: 2007
Grant Type: NHMRC Project Grants
Title of research award:
Is EphA4 the major molecular regulator of axonal regeneration?Is EphA4 the major molecular regulator of
axonal regeneration?
Lay Description (from application):
Spinal cord injury affects a substantial number of Australians each year. Around half the number of spinal
cord injury cases result in quadriplegia, with loss of function to a varying degree in the upper as well as the
lower limbs. The limited degree of repair of spinal axons following injury means that such paralysis is usually
permanent. Although the inability to walk is a serious issue, the limited function of the arms and hands results
in a loss of independence which is a major factor contribuing to the enormous personal, financial, and
community costs of this problem, estimated to cost the Australian community $200 million a year. In recent
years advanced anatomical and molecular approaches to the problem of repair of the central nervous system
have provided great insights into the neuronal and glial reactions to neural damage that appear to govern the
success or failure of neural regeneration. Our preliminary data indicate that a receptor tyrosine kinase, EphA4,
which is important for axonal pathfinding in the developing nervous system, is a potent inhibitor of neural
regeneration following spinal cord injury. In this project we will determine the mechanisms by which EphA4
exerts its inhibitory effects, and examine the effect of neutralizing EphA4 signalling on neural regeneration.
Success in achieving this result will lead to the development of a therapeutic intervention that we will test in
mouse models.
Research achievements (from final report):
This project sought to investigate whether EphA4 was a dominant target for therapy in spinal cord injury. We
have shown that blocking EphA4 by use of soluble Eph inhibitors promotes significant re-innervation and
functional recovery following 2 weeks of treatement. We also showed that the dominant effect of therapy is to
enable re-innervation rather than inhibiting the gliotic response.
Expected future outcomes:
These studies pave the way to the development and testing of therapies for use in human spinal cord and brain
injury.
Name of contact:
Andrew Boyd
Email/Phone no. of contact:
Andrew.Boyd@qimr.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 351519
CIA Name: Dr Sheree Cross
Admin Inst: University of Queensland
Main RFCD: Intensive Care
Total funding: $342,375
Start Year: 2005
End Year: 2007
Grant Type: NHMRC Project Grants
Title of research award:
Management of burn injury: Fluid dynamics and antibiotic pharmacokineticsManagement of burn injury: Fluid
dynamics and antibiotic pharmacokinetics
Lay Description (from application):
It is well known that major burns, as well as being relatively common injuries, are notoriously difficult to
manage. Patients exhibit significant variability due to a combination of anatomic, physiologic, hormonal and
immunologic alterations occurring both at the wound site and, more importantly, in other body compartments
and vital organ systems. Skin burn injury results in the release of multiple inflammatory mediators in addition
to significant fluid loss. The distribution of inflammatory mediators and wound bacteria to central organs can
cause complex physiological changes that may lead to multiple organ failure, with serious infections occurring
in around 50% of patients with serious burns. Antibiotic distribution kinetics, such as bioavailability,
clearance, volume of distribution, elimination half-life and unbound fraction in plasma can be significantly
altered in burn patients. Without detailed knowledge of changes and relationships between factors such as
wound pH, tissue oxygenation, protein concentrations of fluid leaked from the local wound microvasculature,
tissue binding, oedema and changes in burned and non-burned tissue induced by resuscitation therapies, the
optimisation of both local and systemic infection contriol therapies can hardly be expected to advance. This
project aims to determine how changes the physiology of burn patients, in particular in the burn wound
environment, affect antibiotic penetration and distribution into tissues. We also believe that these changes will
vary between patients and are aiming to determine whether certain parameters can be used to give an indication
of the best antibiotic dosing regimens for individual patients.
Research achievements (from final report):
Patients with severe burns are at great risk of life threatening infections. Effective antibiotic therapy is crucial
to the survival of patients with extensive burns and to the optimal operation of hospital burns units. Burn
patient physiology is very complex and changes dramatically over the first week of treatment. Before
commencement of this project there was a lack of scientific data on the use of antibiotics in burn surgery. We
applied a combination of cutting-edge and time-honoured research techniques to thoroughly investigate the
pharmacokinetics of antibiotics during burn debridement operations. We were able for the first time to monitor
local tissue levels of antibiotics throughout burn surgery. The results permitted scientifically qualified
recommendations on perioperative burn antibicrobial prophylaxis to be published. The study identified key
predictors of sub-optimal antibacterial dosing in burn patients and made recommendations for intra-operative
redosing during surgery. Our clinical research was backed by an extensive program of healthy volunteer studies
and laboratory science which has lead to additional evaluative publications in scientific and clinical journals.
Expected future outcomes:
This research is expected to contribute significantly to future optimisation of antimicrobial usage in patients
with burns.
Name of contact:
Sheree Cross
Email/Phone no. of contact:
s.cross@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 351678
Start Year: 2005
CIA Name: A/Pr Deborah Falla
End Year: 2008
Admin Inst: University of Queensland
Grant Type: Early Career Fellowships (Overseas)
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $280,742
Title of research award:
An investigation of the mechanisms of cervical muscle impairment in people with chronic neck pain.An
investigation of the mechanisms of cervical muscle impairment in people with chronic neck pain.
Lay Description (from application):
Not Available
Research achievements (from final report):
Neck pain is a common complaint which affects up to 70% of individuals at some point in their lives with an
increasing incidence. Neck pain is associated with impairment of muscle performance which can be assessed at
a functional level. Functional deficiencies reflect altered mechanisms of muscle control and changed muscle
properties. Although the basic physiological mechanisms underlying pain have been extensively investigated
and the functional impairments associated with neck pain are well documented, the cause-effect relationship
between neck pain and impaired neuromuscular control is poorly understood. This is due to the difficulty in
translating basic physiological findings into the variable and complex scenario of clinical pain conditions.
Given the difficulties in interpreting the relationship between pain and motor control in clinical studies, the
work undertaken during this Fellowship involved experimental induction of neck pain in healthy individuals
with the aim of improving our understanding of the immediate effects of pain on neck muscle function. The
experimental studies conducted have clarified both the direct and indirect effects of neck pain on
neuromuscular function and have assisted in interpreting clinical findings. The results of this research have
contributed to the development of contemporary exercise programs for the management of neck pain. These
exercises have been evaluated in randomized controlled trials and have proven to be effective for reducing neck
pain and disability and for improving neuromuscular control of the spine in people with neck pain.
Expected future outcomes:
It is expected that this work will result in a number of future studies including the evaluation of specific
exercise as a component of a multimodal / multidisciplinary intervention for the management of neck pain and
evaluation of the effect of this intervention on the recurrence of neck pain. ,
Name of contact:
Deborah Falla
Email/Phone no. of contact:
deborah.falla@bccn.uni-goettingen.de
NHMRC Research Achievements - SUMMARY
Grant ID: 353619
Start Year: 2005
CIA Name: Prof Boris Martinac
End Year: 2007
Admin Inst: University of Queensland
Grant Type: NHMRC Project Grants
Main RFCD: Therapies and Therapeutic Technology
Total funding: $424,500
Title of research award:
Bacterial mechanosensitive channels as novel targets for antibacterial agentsBacterial mechanosensitive
channels as novel targets for antibacterial agents
Lay Description (from application):
The focus of this research is the development of new antibiotics to combat bacterial antibiotic resistance. Since
their discovery antibiotics have had a profound effect on the health and well being of mankind, providing ready
effective treatment for otherwise intractable infections. Although pencillin was initially effective against a large
range of infections by the 1950s it was apparent that some bacterial strains had become resistant to this
antibiotic. Partially in response to this resistance new antibiotics such as streptomycin, chloramphenicol and
tetracycline were developed. These new drugs were potent against both Gram-positive and Gram-negative
bacteria. However, there were early signs that resistance to these drugs was also emerging. For example, in
1953, during a Shigella outbreak in Japan, a strain of the dysentery bacillus was isolated which was multi-drug
resistant, exhibiting resistance to chloramphenicol, tetracycline, streptomycin and the sulfanilamides.
Multidrug-resistance in pathogenic strains of bacteria has in the last decade presented an increasing problem in
treatment of bacterial infections and diseases. In 1994 a Melbourne public hospital reported a new antibiotic
resistant strain of bacteria. This bacterium was resistant to vancomycin (the antibiotic used when all others
have failed) and is known as VRE or vancomycin resistant enterococcus. Now strains of "golden staph"
resistant to all antibiotics have appeared. The re-emergence of tuberculosis (TB), which kills more than 3
million people annually and which is spreading rapidly throughout the world, is also a serious threat,
particularly as many strains are now multi-drug resistant. New antibiotics are needed that overcome bacterial
drug resistance. It is anticipated that this research will lead to new antibiotics by exploiting molecular
components of bacteria that have only recently been identified.
Research achievements (from final report):
In this project we have completed a series of experiments testing a number of different compounds including
parabens (alkyl esters of p-hydroxybenzoic acid) as well as eriochrome cyanine R and its derivatives in
functional patch-clamp experiments and shown that they acted as bacterial MS channel (MscL and MscS)
openers (Nguyen et al., 2005). Using in silico ligand docking and ligand database canning of 2000 compounds
we have identified 20 further compounds, which could serve as lead compounds in development of novel
antibiotics targeting MscL channels. Several of these compounds were tested in vitro by the patch clamp, in
vivo (growth assays) experiments and by electron spin resonance (EPR) spectroscopy. A PhD thesis describing
a project based on this research was accomplished last year (T. Nguyen: The pharmacology of the
mechanosensitive channels of Escherichia coli. PhD thesis, University of Western Australia, 2007). An
Honours (First Class) project on in silico studies of several of the 20 compounds was accomplished in 2005 (R.
Boulos: Bacterial mechanosensitive channels as novel targets for anti- bacterial agents, Honours thesis,
University of Western Australia, 2005). This has been followed by chemical synthesis of novel compounds in a
PhD project (R. Boulos) that started at the beginning of 2006. We also used two different testing methods, the
checkerboard and the disk diffusion methods, to compare in vivo efficacies of eriochrome cyanine in
combination with macrolides, aminoglycosides and penicillins against two pathogens, E.faecalis and S.aureus.
In addition, we tested by the patch clamp the effect of the spider peptide GsMTx4 shown to have antibacterial
properties on the activity of MS channels of small conductance of E. coli.
Expected future outcomes:
Further screening and investigations of potential lead compounds for novel type of antibiotics targeting MS
channels of bacterial pathogens based on this project should in not too distant future result in patentable
compounds, which could be tested in animal cells and animal models.
NHMRC Research Achievements - SUMMARY
Name of contact:
Prof Janet M Wood, University Of Guelph, Canada
Email/Phone no. of contact:
jwood@uoguelph.ca
NHMRC Research Achievements - SUMMARY
Grant ID: 401553
CIA Name: Prof Mark Forwood
Admin Inst: University of Queensland
Main RFCD: Orthopaedics
Total funding: $412,653
Start Year: 2007
End Year: 2008
Grant Type: NHMRC Project Grants
Title of research award:
Molecular and histopathological investigation of stress fracture healing and effects of anti-inflammatory
drugs.Molecular and histopathological investigation of stress fracture healing and effects of anti-inflammatory
drugs.
Lay Description (from application):
Stress fractures are debilitating injuries affecting children, adolescents and adults in sport, and army recruits.
They also occur in horse and greyhound racing, often resulting in euthanasia of the animals involved. They
incur considerable costs in medical expenses, time lost from sport and interruption to military training. But,
there is almost no information on the mechanism of healing of these fractures. Non-steroidal anti-inflammatory
drugs (NSAIDs) are still the most widely used medication in management of musculoskeletal injuries, yet their
effect on healing of stress fractures is unknown. NSAIDs delay fracture healing, but until recently there has
been no standardised way of studying stress fractures. We have created, for the first time, a well-characterised,
non-invasive model of stress fractures in the forearm of rats that closely resembles the clinical situation. This
provides a novel and unique opportunity to determine the histological and molecular mechanism of stress
fracture healing, and to investigate effects of antiinflammatory/analgesic medications on this process. Rats will
have an experimental stress fracture produced in one forelimb, and its healing will be examined up to ten
weeks using microscopic investigation and analysis of the genes that are turned off or on to initiate the process.
Groups of rats will also be treated with antiinflammatory drugs such as ibuprofen, specific COX-2 inhibitors
and a new class of drugs that target early immune responses called C5a receptor antagonists. The analgesic
Paracetamol will also be investigated as an alternative to the NSAIDs described above. There is widespread use
of anti-inflammatory agents in managing stress fractures, so it is vital that their effects on stress fracture
healing be examined. This project has enormous significance for optimising approaches for clinical
management of stress fractures and for understanding the interaction of anti-inflammatory or analgesic agents
in that process.
Research achievements (from final report):
1. We have provided the first detailed analysis of the biological mechanisms of healing of stress fractures., 2.
We have reported original observations on gene expression for molecules that are important to signal new bone
remodelling that is targeted towards healing the stress fracture. These data were accepted for oral presentation
at the Annual Meeting of the American Society of Bone and Mineral Research, the largest international
meeting in the field at which only 30% submissions achieve orals. This work attracted a New Investigator
Award for Ms Lisa Kidd who presented the data (these data accepted for publication in the journal Bone)., 3.
We demonstrated that non-steroidal anti inflammatory drugs retard the rate of healing of stress fractures, with
distinct effects on bone formation or resorption depending on the specificity of their action., 4. We
demonstrated that osteoporosis drugs like bisphosphonates retard the early resorption phase of remodelling of
stress fracture healing., These outcomes provide unique insights in to the mechanisms of healing of stress
fractures that may inform approaches to surgical intervention in the case of non-healing stress fractures. They
also highlight the potential for altered healing when common aniinflammatory drugs are used, or stress
fractures occur in the context of anti-resorption therapy.
Expected future outcomes:
Based on these data, we are investigating an approach to re-activate bone remodelling at sights where stress
fracture healing is incomplete
Name of contact:
Mark Forwood
NHMRC Research Achievements - SUMMARY
Email/Phone no. of contact:
m.forwood@griffith.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 401565
CIA Name: Prof Brian Key
Admin Inst: University of Queensland
Main RFCD: Sensory Systems
Total funding: $496,321
Start Year: 2007
End Year: 2008
Grant Type: NHMRC Project Grants
Title of research award:
Deciphering the mechanisms for constructing the olfactory systemDeciphering the mechanisms for
constructing the olfactory system
Lay Description (from application):
The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life
and it can regenerate even after injury. It therefore provides an excellent model for examining the growth,
development and maintenance of nerve cells. This project will examine the effects on the organisation of the
olfactory system when some guidance signals are altered. Information we obtain about how this system
develops and regenerates may be useful in treating brain disorders and spinal injuries The results of these
experiments will provide important information on the the initial growth and targeting of these nerve cells
which may have implications for regeneration of these as well as other nerve cells.
Research achievements (from final report):
The essential steps in forming a normal functioning brain occur during life as an embryo. If these processes go
haywire, there can be serious repercussions for life after birth. This project has understand how the brain forms
during embryonic stages so that better treatments and procedures can be developed to deal with developmental
problems.
Expected future outcomes:
There is know the opportunity to identify particular molecules that are responsible for key developmental
events in brain formation. These molecules are potential drug targets that could be used for therapeutic
purposes.
Name of contact:
Brian Key
Email/Phone no. of contact:
brian.key@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 401579
CIA Name: A/Pr Peter Noakes
Admin Inst: University of Queensland
Main RFCD: Cellular Nervous System
Total funding: $463,145
Start Year: 2007
End Year: 2008
Grant Type: NHMRC Project Grants
Title of research award:
The role of central and peripheral synaptic activity in the developmental death of motoneurons.The role of
central and peripheral synaptic activity in the developmental death of motoneurons.
Lay Description (from application):
Information processing in the nervous system relies on the effective communication between neurons and their
target cells which make up our neuronal circuitry. At the centre of all this is the synapse, the specialized
contact between a neuron and its target cell, be it another neuron in the brain or a target organ such as skeletal
muscle. Our primary goal is to determine how the formation of synaptic connections during development
regulates neuronal survival. In this proposal we have focussed on the neuromotor system as it is a well
characterised part of the nervous system. During development, 50% of motoneurons die at a time when they
are making contact with skeletal muscle, and when contacts onto motoneurons by other neurons are being
established. We believe that the formation of effective synaptic contacts onto motoneurons, as well as
connections by motoneurons onto muscle are the key regulators of motoneuron survival. We are in a position
to be able to address what regulates motoneuron death; as we have a number of mice which lack key molecules
needed for the formation of specialisations that allow neuronal contacts to be made between motor neurons and
their muscle, and with other neurons within the spinal cord. By examining the function of motoneurons,
counting them and screening for molecular changes in these mice, we will be able to dissect out the mechanism
of how a motoneurons' fate is determined during developmental motoneuron death. This research could help in
developing strategies aimed at improving neuronal connections to improve neuronal viability. Our research will
have important implications for our understanding about the basis of adult neuro-degenerative diseases, such as
motor neuron disease and Alzheimer's, which are in part characterised by a molecular breakdown in neuronal
connections that ultimately result in neuronal death.
Research achievements (from final report):
The role of synaptic activity in determining motoneuron (MN) survival is a key question in the developing
neuromotor system. In this grant, we have shown that genetic manipulation of neuromuscular synaptic activity
shows that relay of central synaptic activity to the periphery (muscle) is important. We have also demonstrated
that glycinergic and to a lesser extent GABAergic transmission, plays an essential role in regulating central
neural circuit activity, during the development of the neuromotor system. Specific achivements include: , 1)
Mice missing postsynaptic specializations at neuromuscular synapses shows increased MN survival during
development. We are writing this up. By contrast, mutations to genes that encode for transcription factors that
govern the number of post-synaptic receptor (e.g. Gabp-a) in muscle doesn't alter innervating MN numbers.
This we have published (PN12)., 2) Mice lacking GABAergic transmission show regional changes in MN
numbers. This change is depends upon the switch from excitatory to inhibitory transmission for this
neurotransmitter, which occurs in a rostral to caudal sequence during development. We are examing if altering
Glycinergic and GABAergic transission during developent leads to changes in MN morphology within the
spinal cord. Such changes are likely to determine the number of pre-synaptic connections made onto MNs by
other neurons within the spinal cord. We expect to write later this year (2009). Parts of this work was presented
at the following meetings: Soc. Neurosci (USA) 2007; 4th Internat. Congress of Federation of Asian and
Oceanic Neurosci. Soc. Hong Kong (2006); ComBio Conf. (2007; 2008); and Aust. Soc. Neurosci.(2009).
Expected future outcomes:
1) Submit for publication the above mentioned papers ( 2to 3 publications). , 2) Create novel mutant lines of
mice that will allow us to determine if there is a direct influence of pre-synaptic connections on the
development and survival of motoneurons, independent of muscle feedback to motoneurons.
Name of contact:
NHMRC Research Achievements - SUMMARY
Peter G. Noakes
Email/Phone no. of contact:
p.noakes@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 401598
Start Year: 2006
CIA Name: Prof Paul Hodges
End Year: 2008
Admin Inst: University of Queensland
Grant Type: NHMRC Project Grants
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $296,453
Title of research award:
Pain and trunk muscle control: Effects, mechanisms and consequencesPain and trunk muscle control: Effects,
mechanisms and consequences
Lay Description (from application):
Twenty-one percent of Australians report long-term back problems. This makes back pain the most common
chronic pain in Australia and most prevalent disorder among the National Health Priority Areas. For the
majority with recurrent and chronic problems, the cause is unknown but changes in control of the spine are
thought to be important. It is well accepted that pain and injury to the low back affect the way that we control
the back muscles and this leads to changes in spinal function. However, despite considerable investigation of
this problem, there is a distinct lack of consensus for how the control of movement is changed during pain, why
it changes, and whether these changes lead to further problems in the long term. The objective of this series of
studies is to determine how the adaptation to pain changes the control of the spine. We will use a range of
techniques that include tests of the strategies used by the brain to control the spine and mathematical models to
estimate the effect that these changes have on the spine when people are given back pain by injecting sterile
salty water into the back muscles. These studies will be backed up by measures of mechanical properties of the
spine and by comparison to people with clinical pain. This combination of methods has not been used
previously and is likely to help resolve the problem of how muscle control is chaged in back pain. We will also
test a range of hypotheses regarding how pain has its effect on muscle activity. A final series of studies aims to
determine whether the failure of these changes in muscle control to resolve after an epiosde of back pain leads
to increased recurrence of pain in the long-term. The importance of this project is highlighted by the
significance of back pain as a major health issue, the lack of consensus regarding the effect and mechanisms of
pain on trunk muscle control (despite extensive investigation), and the potential for the findings to guide
rehabilitation and management.
Research achievements (from final report):
The results of this program of research have redefined the understanding of how movement changes in people
with back pain. In recent years there has been an explosion of exercise interventions that aim to make the spine
more stable. Terms like "core stability" and "stabilisation exercise" are commonly used to describe exercise for
back pain in gyms and the media. This exercise approach is based on the assumption that the spine is unstable.
We proposed a different hypothesis, that many people with back pain use strategies to increase spine stability
to prevent further pain and injury, and that these "protective" strategies may be problematic in the long-term.
This series of studies developed novel methods to study mechanical spine properties and control of trunk
muscles in healthy individuals, and people with clinical or experimentally induced back pain. Results showed
that rather than being unstable, people with back pain have increased stiffness and this is associated with
increased muscle activity consistent with protection of the spine. Other studies provide understanding of the
underlying mechanisms for these changes and the potential negative consequences. The studies also provide
the first evidence that dynamic control is compromised in back pain, which is a new target for intervention. In
summary this research challenges the assumptions of a very common clinical intervention and provides new
directions for future developments for management of people with back pain, which is one of the most
common and costly health conditions in Australia.
Expected future outcomes:
This work has provided the basis for a new program or research that aims to investigate the association
between spine control and recurrence or persistence of back pain, and the association with psychological and
social parameters. The research also opens avenues for development and refinement of rehabilitation strategies.
Name of contact:
NHMRC Research Achievements - SUMMARY
Paul Hodges
Email/Phone no. of contact:
p.hodges@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 401599
Start Year: 2006
CIA Name: Prof Paul Hodges
End Year: 2010
Admin Inst: University of Queensland
Grant Type: Established Career Fellowships
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $664,574
Title of research award:
Uncoupled Research FellowshipUncoupled Research Fellowship
Lay Description (from application):
Not Available
Research achievements (from final report):
Movement is changed in pain, but the mechanism underlying this change has been poorly understood. Works
undertaken over the five years of this Principal Research Fellowship has led to a new understanding of not only
the mechanisms that cause movement to change (culminating the development and publication of a new theory
to explain the movement adaptation in pain), but also the development of new interventions to treat pain related
to the spine and the limbs, clinical trials that confirm the efficacy of these approaches, trials that show why
these interventions are effective, and initial evidence of techniques to identify individuals who may derive
greatest benefit from the exercise programs. The work highlighted changes in the function and organisation of
the nervous system including the motor regions of the brain in people with pain, and the potential for this to be
resolved with exercise. Long-term studies revealed that conditions that compromise the function of the back
muscles, such as incontinence and breathing disorders, are associated with development of spinal pain,
providing potentially modifiable risk factors for pain. Other work has identified changes in coordination of leg
muscles in triathletes at risk of stress fracture, changes in control of back muscles in older people with
osteoporosis and fractures of the spinal vertebra, mechanisms for back pain in horses, an new understanding of
mechanisms for the control of continence in men and women.
Expected future outcomes:
Future work, based on the foundations set during the Principal Research Fellowship, is anticipated to identify
clinical techniques to identify individuals with back pain who are likely to benefit most from exercise
interventions and methods to best individualise treatments. Other work aims to identify men at risk for urinary
continence after prostatectomy and more effective methods for treatment.
Name of contact:
Paul Hodges
Email/Phone no. of contact:
p.hodges@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 455836
CIA Name: Prof Matthew Brown
Admin Inst: University of Queensland
Main RFCD: Quantitative Genetics
Total funding: $677,383
Start Year: 2007
End Year: 2011
Grant Type: Established Career Fellowships
Title of research award:
Uncoupled Research FellowsUncoupled Research Fellows
Lay Description (from application):
I am a clinican-scientist and rheumatologist studying genetic determinants of common chronic human
musculoskeletal diseases. My research aims are to define for key genes how specific genotypes promote diease
phenotypes, using in vitro and in vivo approac
Research achievements (from final report):
I have developed human gene mapping approaches using genomewide association studies and next generation
sequencing. In doing so I have identified genetic loci associated with a wide variety of common and rare
diseases including ankylosing spondylitis, rheumatoid arthritis, osteoporosis, multiple sclerosis, psoriasis, and
ocular diseases. I have contributed to the development of study designs for genetic studies, and pioneered the
use of sequencing based approaches in human genetics. My group has also determined mechanisms underlying
genetic associations with disease, notably in ankylosing spondylitis investigating the mechanisms of
association of the genes IL23R and ERAP1, from which therapies are either in use or in development
respectively.
Expected future outcomes:
I expect my research will lead to the development of curative therapies for the common autoimmune disease
ankylosing spondylitis, and likely psoriasis and inflammatory bowel disease.
Name of contact:
Matthew Brown
Email/Phone no. of contact:
matt.brown@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 455863
Start Year: 2007
CIA Name: Prof Paul Hodges
End Year: 2012
Admin Inst: University of Queensland
Grant Type: Centre of Clinical Research
Excellence
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $2,007,200
Title of research award:
CCRE in Spinal Pain, Injury and HealthCCRE in Spinal Pain, Injury and Health
Lay Description (from application):
Spinal complaints present the greatest social and economic burden of musculoskeletal conditions in Australia.
This reflects current realities: the cause remains unknown; 80% of the population is affected; and isolated
professions perform a staggering array of interventions. The CCRE aims to target these realities and improve
Australia's capacity to prevent and manage spinal disorders by supporting innovative interdisciplinary research
and training. This community- and university-based centre will align highly successful clinical and basic
researchers in collaboration with a national network of spine scientists to foster interdisciplinary clinical
researcher training, develop new diagnostics and therapeutics, and translate findings to the community.
Through clinical research the centre aims to: (i) Advance understanding of physiology and pathophysiology of
spinal pain (ii) Translate findings from basic research to clinical practice (iii) Establish coordinated
multidisciplinary research to reduce the burden of spinal pain (iv) Predict and prevent the transition from acute
to chronic states (v) Train a new generation of transdisciplinary clinical scientists (vi) Rapidly assess new
treatment possibilities in pre-clinical studies (vii) Develop innovative technologies for diagnostics and
therapeutics (viii) Encourage Australian commercialisation opportunities for new discoveries (ix) Encourage
community-user participation in direction of research programs (x) Disseminate new findings and information
of evidence-based practice to patients, clinicians, insurers, government and the scientific and wider community
Research achievements (from final report):
The Centre of Clinical Research Excellence in Spinal Pain, Injury and Health (CCRE SPINE) aimed to
improve the outcomes for people with spinal pain through research, research training, and translation of
research findings to practice. Highlights include the following. Major research outcomes include identification
of novel brain changes in spinal pain (awarded the major international back pain prize), identification of
mechanisms for transition from acute to chronic pain, and evaluation of efficacy of treatments. A key research
achievement involved organisation of two "Summit" meetings of world experts to establish consensus opinion,
a research agenda and new collaborations to address; (i) mechanisms of transition from acute to chronic pain,
and (ii) relationships between spine control, spine pain and rehabilitation. Outcomes were published as a major
text (Elsevier) and a special issue of the leading journal (Spine). Multiple papers, grants and new initiatives
evolved from new collaborations. Training not only supported doctoral students and post-doctoral researchers,
but also a unique program to involve clinicians in research. Twelve clinicians were supported to undertake
research. Outcomes include published papers, conference presentations, and enrollment of clinicians in
doctoral programs (three completions to date).Translation of research findings to patients and clinicians was a
major focus. Major achievements include completion of a patient-focused website to enable people with
whiplash associated disorders to compare evidence for treatments in a clear understandable manner, extensive
research regarding the information needs of patients with low back pain, and patient forums and clinician
training in Australia, Europe and North America.
Expected future outcomes:
New collaborations arising from "Summit" meetings have produced novel multidisciplinary research
paradigms and grants. Training programs enhanced clinician involvement in research as a foundation to narrow
the gap between clinical practice and research. Extensive qualitative research laid the foundation for
development of a patient centered web resource for back pain.
Name of contact:
Paul Hodges
NHMRC Research Achievements - SUMMARY
Email/Phone no. of contact:
p.hodges@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 455941
CIA Name: Dr Allison Pettit
Admin Inst: University of Queensland
Main RFCD: Orthopaedics
Total funding: $564,964
Start Year: 2007
End Year: 2009
Grant Type: NHMRC Project Grants
Title of research award:
Role of bone-associated macrophages in bone remodelling and bone diseaseRole of bone-associated
macrophages in bone remodelling and bone disease
Lay Description (from application):
Musculoskeletal diseases, including osteoporosis and osteoarthritis, are a national and international health and
research priorities. Over 3 million Australians suffer from arthritis and musculoskeletal conditions and their
social and economic impact is expected to dramatically increase in the next 20 years as a result of the aging
population. Early diagnosis, prevention and treatment of many musculoskeletal diseases are currently
inadequate. Consequently, there is a high demand for effective treatment options. This project grant application
proposes a novel line of scientific investigation that will provide greater understanding of the contribution of
macrophages (a cell type that has important roles in normal tissue maintenance and defense against infection)
in bone remodelling and disease. Bone is continuously remodelled and replaced to maintain skeletal strength
and mineral metabolism. We have shown that a population of macrophages is intimately associated with bone
and propose that these cells play an important part in regulating bone remodelling. Macrophages have been
implicated in many diseases that have damaging consequences on bone, including osteoporosis and several
forms of arthritis, linking aberrant macrophage function to disease-associated bone damage. This project aims
to characterize this population of bone-associated macrophages and determine their ability to influence the
function of other cells integrally involved in bone remodelling. We will also undertake studies in animal
models to determine whether these cells are required for bone remodelling and/or damage. Detailed description
of the novel role of macrophages in bone biology will facilitate the development of superior therapeutics,
preventatives and cures for bone diseases.
Research achievements (from final report):
Bone diseases and injury have substantial social and economic impact both nationally and internationally.
Osteoporotic hip fractures alone are predicted to cost $240 billion annually by 2045 in the USA. These
statistics clearly indicate the importane of maintaining lifelong bone health and preventing and/or improving
fracture repair. There are few effective bone building treatments available and their development is a clear
research priority. Research undertaken during this project grant showed that a discreet population of
macrophages (traditionally an immune cell) reside in the specilized tissues associated with bones. We
designated this macrophage population 'osteomacs'. Data indicated that osteomacs are unlikely to be a
precursor population for the related osteoclast cell (specilized cell that removes bone). Strikingly, osteomacs
were stratigically located at sites of new bone formation. Presence of osteomacs in both mouse and human
tissues was confirmed using a combination of macrophage specific marker molecules and cell location. Using
multiple approaches molecular markers that distinguished osteomacs from other closely related macrophage
populations were not yet discovered. However, specific cell culture conditions were developed to generate an
osteomac-like population that promoted bone generation by osteoblast (specialized bone building cells).
Subsequently osteomac-expressed factors that potentially induce this bone formation outcome were identified.
In a bone injury model, osteomacs were required for optimal bone formation during healing. Notably, treatment
with a factor that increased osteomacs within bone injury sites also increased bone formation and accelerated
bone repair. This study demonstrated that osteomacs are an unexpected and important cell participant in bone
formation.
Expected future outcomes:
Osteomacs are prime cellular targets for promoting bone repair and development of treatments that either
enhance or replicate osteomac function will improve outcomes in bone diseases and fracture repair.
Identification of osteomacs reveals greater links between the immune and bone systems and the potential for
both benefit and detriment of immune contributions to bone disease/injury.
NHMRC Research Achievements - SUMMARY
Name of contact:
Allison Pettit
Email/Phone no. of contact:
a.pettit@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 456003
CIA Name: A/Pr Geoffrey Goodhill
Admin Inst: University of Queensland
Main RFCD: Biophysics
Total funding: $493,305
Start Year: 2008
End Year: 2009
Grant Type: NHMRC Project Grants
Title of research award:
The dynamics of gradient sensing by growth cones: timelapse imaging and mathematical modellingThe
dynamics of gradient sensing by growth cones: timelapse imaging and mathematical modelling
Lay Description (from application):
Problems in the wiring up of the brain underlie several nervous system disorders. The goal of this project is to
understand better how this wiring normally forms. This will ultimately lead to a better understanding of what
can go wrong with brain wiring, and how to fix such problems. It will also lead to a better understanding of
how to make axons regenerate after injury. Our approach is to use a combination of timelapse imaging of
neurons in culture, and mathematical modelling, to understand how the tips of the wires growing between
neurons sense their environment. By comparing our experimental measurements with our theoretical results we
will arrive at a detailed and accurate model of this sensing process. This will allow us to make predictions
about how these developmental events normally occur in vivo, and what can go wrong.
Research achievements (from final report):
Axon guidance by molecular gradients plays a crucial role in wiring up the nervous system. However, the
mechanisms axons use to detect gradients are largely unknown. This project combined theoretical modelling
with quantitative experimental measurements of axon trajectories and the behaviour of neuronal growth cones
in precisely controlled molecular gradients. Firstly, we developed a Bayesian "ideal observer" analysis of
gradient detection by axons, based on the hypothesis that a principal constraint on gradient detection is intrinsic
receptor binding noise. Secondly, from this model we derived an equation predicting how the degree of
response of an axon to a gradient should vary with gradient steepness and absolute concentration. Thirdly, we
confirmed this prediction quantitatively by performing the first systematic experimental analysis of how axonal
response varies with both these quantities, using the response of rat dorsal root ganglia to gradients of nerve
growth factor as a model system. We found experimentally that a measurable response can be seen to gradients
as shallow as 1 molecule per millimetre, a degree of sensitivity much higher than previously reported for any
chemotacting system. Together these results reveal both the quantitative constraints that must be satisfied for
effective axonal guidance and the computational principles that may be employed by the underlying signal
transduction pathways, and allow predictions for the degree of response of axons to gradients in a wide variety
of in vivo and in vitro settings.
Expected future outcomes:
N/A
Name of contact:
Prof Geoffrey Goodhill
Email/Phone no. of contact:
g.goodhill@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 456040
CIA Name: A/Pr Helen Cooper
Admin Inst: University of Queensland
Main RFCD: Cellular Nervous System
Total funding: $513,947
Start Year: 2007
End Year: 2009
Grant Type: NHMRC Project Grants
Title of research award:
Wnt-Ryk signaling in the establishment of major axon tracts in the embryonic mouse brainWnt-Ryk signaling
in the establishment of major axon tracts in the embryonic mouse brain
Lay Description (from application):
The corpus callosum is the major interhemispheric commissure in the human brain, comprising approximately
3 million myelinated fibers which connect homologous regions in the neocortex. To date more than 50
different human congenital syndromes have been described in which the corpus callosum does not form
leading to epilepsy and mental retardation. We have identified a new guidance molecule (Ryk) which is crucial
for corpus callosum formation. This project aims to dissect that molecular mechanisms controlling Ryk
signaling during corpus callosum development. Our analysis of Ryk function will advance our understanding
of the molecular mechanisms underlying the formation of this important commissure.
Research achievements (from final report):
This project has provided fundamental insights for basic researchers interested in identifying the molecular
pathways controlling the formation of the mammalian brain. Identification of these signaling molecules will
lead to a better understanding of how nerve fibres grow and precisely navigate to their correct targets elsewhere
in the nervous system. Moreover, this knowledge will enhance our undestanding of stem cell biology and the
production of new neurons in both the embryo and adult., This project will also benefit clinicians, as well as the
general public, as it will provide important knowledge for understanding the aberrant molecular mechanisms
underlying the failure of nerve tract formation in the brain. Such failures lead to autism, many forms of mental
retardation, and epilepsy. We have also identifed new compounds that may enhance the regrowth of axons after
injury due to trauma or neurodegeneration.
Expected future outcomes:
Our discoveries will: , o
provide the groundwork for more
detailed studies on the fundamental molecular mechanisms underlying brain development., o provide a
greater understanding of the mechanisms reponsible for autism, mental retardation and epilepsy., o identify
novel drugs with the potential to promote regeneration of nerve tracts after injury.
Name of contact:
Helen Cooper
Email/Phone no. of contact:
h.cooper@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 456106
CIA Name: Prof Roy Kimble
Admin Inst: University of Queensland
Main RFCD: Surgery
Total funding: $209,669
Start Year: 2007
End Year: 2009
Grant Type: NHMRC Project Grants
Title of research award:
First aid for burns: the use of ice water and ice?First aid for burns: the use of ice water and ice?
Lay Description (from application):
Millions of people worldwide receive burn injuries every year and last year the Royal Children's Hospital in
Brisbane alone treated more than 500 children with new burn injuries. Many of these children with burn
injuries will heal burn wounds with unsightly scars and impaired skin function. Cooling burns as first aid has
been used since ancient time and is proved to be the most effective way to reduce skin temperature, lessen pain,
minimize the depth of injury, and ultimately improve wound healing outcome. However, despite the evidence
that cooling burns using ice water <4 C may be beneficial to burns, current first aid recommend to only use
cold water 8-25 C and the use of ice/ice water is strongly discouraged for fear of the potential to cause
hypothermia and deepen the existing burn injury. In this application we will examine the effect of ice/ice water
2 C on wound healing outcome compared to 15 C water as first aid, in an in vivo model. The wound healing
will be clinically assessed by experienced clinicians weekly for six weeks, and then will also be assessed
histologically and mechanically at week six. We will also determine the optimal cooling temperature and
duration for injured tissue in burn wounds to recover and the conduction of cold through skin. With the coming
new knowledge we wish to design an optimal cooling burn treatment which will maximize the beneficial of
cooling to the burns but avoid adverse effect of excessive cooling. The success of this project will advance our
knowledge on first aid treatment or burn cooling treatment and also wound healing process. It will enable us to
offer better first aid treatment which may lead to wound healing with less scars, otherwise can not achieved by
other current available treatments. The better healing of burn wounds will significantly improve burn patients'
lives, particularly children with burn injuries. It will also release the burden on much needed health funds.
Research achievements (from final report):
This project has provided in vivo evidence to support the use of first aid on burns using a large animal model
where skin closely resembles humans and has advanced our current knowledge and the mechanism of the first
aid on burn wound healing., The findings from this project support the current first aid guidelines of immediate
application of cold tap water (approximately 15C) for 20 minutes and recommend the delay application of cold
tap water even up to 3 hours post-burn. Additionally, it finds that 2C water is beneficial to burn wound healing
and, nonetheless, has limited clinical application as first aid due to its close association with hypothermia. Ice
should not be used as first aid for burns. This project also shows that other popular alternative first aid, such as
aloe vera and tea tree oil, has no beneficial effect on burn wound healing. The findings of this project
demonstrate unknown factors other than reducing the temperature of burns may contribute to the better
outcome of burn healing for cold running water, since both ice and 2C running water can equally and
effectively cool burns and ice does not enhance burn wound healing. This project does not find that ice/ice
water is detrimental to burn wounds as some suggested in this field., The findings from this project re-define
the burn first aid and reinforce the importance of the proper application of burn first aid. This valuable
information will be available to relevant regulatory bodies for the formulation of optimal burn first aid. This
information will also reach to general public through media and awareness campaigns.
Expected future outcomes:
The findings from this project will lead to revised guidelines for burn first aid which will then be used to
educate the public. The increased application of optimal burn first aid will be followed in general public and in
hospitals. This will ultimately leads to significantly less scarring from burn healing and consequently improve
burn patients' lives, particularly children with burn injuries.
Name of contact:
Roy Kimble
NHMRC Research Achievements - SUMMARY
Email/Phone no. of contact:
royk@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 511161
Start Year: 2008
CIA Name: A/Pr Michel Coppieters
End Year: 2011
Admin Inst: University of Queensland
Grant Type: NHMRC Project Grants
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $370,069
Title of research award:
Clinical efficacy and physiological mechanisms of nerve and tendon gliding exercises for carpal tunnel
syndromeClinical efficacy and physiological mechanisms of nerve and tendon gliding exercises for carpal
tunnel syndrome
Lay Description (from application):
Compression of one of the major nerves at the wrist (carpal tunnel syndrome) is a very common condition that
significantly impacts on the well-being of the patient. To date, there is no good evidence that traditionally
advocated interventions are effective in the long term. This project will evaluate the effects of a novel, active
treatment strategy and will investigate the underlying mechanisms that may be associated with exercises that
aim to mobilise the nerve and tendons at the wrist.
Research achievements (from final report):
As anticipated, the program of studies of Project Grant 511161 has significantly improved our understanding of
the conservative management of carpal tunnel syndrome (CTS), which is the most common nerve entrapment
(prevalence ~3% in the general population). A successfully conducted, large randomised clinical trial revealed
that both multimodal physiotherapy and an electrophysical agent (ultrasound) significantly improved pain and
function, but physiotherapy was more efficient (9 versus 20 treatments). Interestingly, although wearing a wrist
splint at night and during aggravating activities is widely recommended by hand therapists and GPs, the
clinical trial revealed that wearing a splint was actually associated with poorer outcome. An expansion of this
trial, not proposed in the original application, revealed that - other than commonly assumed - the majority of
patients with clinical signs and symptoms of CTS, but a negative nerve conduction test, have unfavorable
outcomes at long term follow-up (1 to 3 years). A series of physiological studies revealed that nerve and tendon
gliding exercises were able to reduce intraneural oedema and nerve compression. Other studies not proposed in
the original grant application, but closely linked and facilitated by the grant, revealed that ergonomic computer
divices commonly advocated for patients with CTS (and widely implemented) did not alter the physiological
processes they are believed to influence (such as limiting the increase in carpal tunnel pressure during
computer operation).
Expected future outcomes:
The data from the randomised clinical trial are currently mined to identify factors associated with poor
outcome. Since the commencement of the trial, new insights in CTS have emerged (e.g., identification of
central nervous system sensitisation in CTS). Clinical signs of central sensitisation are incorporated in the
prognostic study and are anticipated to be associated with poor outcome.
Name of contact:
Michel W Coppieters
Email/Phone no. of contact:
m.coppieters@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 511212
CIA Name: Prof Perry Bartlett
Admin Inst: University of Queensland
Main RFCD: Central Nervous System
Total funding: $622,361
Start Year: 2008
End Year: 2010
Grant Type: NHMRC Project Grants
Title of research award:
The use of soluble antagonists of EphA4 in spinal cord injuriesThe use of soluble antagonists of EphA4 in
spinal cord injuries
Lay Description (from application):
Permanent and limited recovery of function following spinal cord injury is a direct result of the lack of nerve
regrowth through the injury. Our preliminary data suggest that antagonising the effects of EphA4, a protein
involved in brain development, leads to substantial functional recovery simultaneous with nerve regrowth. In
addition to designing new, more effective blockers of EphA4, we will study the signalling pathways that
EphA4 activates to inhibit nerve regrowth.
Research achievements (from final report):
Spinal cord injuries result in movement and sensory deficits for individuals. With no successful drug or
treatment to improve recovery from spinal cord injuries currently available, suffers of spinal cord injuries
generally experience permanent movement and sensory loss. We have previously shown that mice lacking the
EphA4 receptor display remarkable functional recovery after a lateral cut to their spinal cord. In addition, these
mice demonstrate nerve regeneration across the cut site. In this grant, we generated and tested a recombinant
protein, EphA4-Fc, for its use as a future therapeutic. EphA4-Fc blocks the EphA4 receptor, preventing its
activation. When EphA4-Fc is delivered after injury in normal mice, their functional recovery is significantly
improved compared to untreated mice, duplicating the effects we observed in mice that lack the EphA4
receptor. We have now tested this protein in rats with a contusive spiinal cord injury. This injury more closely
mimics that which is observed in humans. Treated rats also show significant improvements in their functional
outcomes compared to untreated rats. EphA4-Fc does not show any adverse side effects during or after
treatment. Antagonists of EphA4 are proving to be promising candidates for therapeutics for not only spinal
cord injury, but possibly other traumatic central nervous system injuries as well.
Expected future outcomes:
We have demonstrated that EphA4-Fc has considerable therapuetic potential for the treatment of spinal cord
injuries. We are currently performing optimisation and other pre-clinical studies that will justify the significant
investment to proceed to clinical trials.
Name of contact:
Professor Perry Bartlett
Email/Phone no. of contact:
pa@qbi.uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 511238
Start Year: 2008
CIA Name: Prof Guglielmo Vicenzino
End Year: 2012
Admin Inst: University of Queensland
Grant Type: NHMRC Project Grants
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $373,394
Title of research award:
Optimising corticosteroid injection for lateral epicondylalgia with physiotherapy: a randomised placebo control
trial.Optimising corticosteroid injection for lateral epicondylalgia with physiotherapy: a randomised placebo
control trial.
Lay Description (from application):
Tennis elbow affects just under 1% of patients seeing a doctor and on average 10-30% need to take 12 weeks
off work. Two popular treatments are physiotherapy and corticosteroid injections. We have recently shown that
whilst injection is superior in the short term (3 weeks) compared to physiotherapy, it is responsible for 9 times
more recurrences. We seek a solution for the downside to steroid injections, by studying the effects of adding
physiotherapy; as such it will address a major problem.
Research achievements (from final report):
This project found that adding a previously proven program of physiotherapy to a corticosteroid injection for
tennis elbow did not alter the path to recovery or recurrence of the injection as it was anticipated from clinical
opinion. In addition, the corticosteroid effects were superior to that of placebo in the short term, but inferior in
the longer term when considering recovery and recurrence rates. These results caution against use of
corticosteroid injections as a first line treatment for tennis elbow even when combined with a course of
physiotherapy.
Expected future outcomes:
Clinical guidelines for tennis elbow should reflect that corticosteroid injections with or without physiotherapy
ought not be the first line of treatment. Patients' informed consent should include both short term success
weighed against risk of delayed recovery and recurrence.
Name of contact:
Bill Vicenzino
Email/Phone no. of contact:
b.vicenzino@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 519702
CIA Name: Prof Jeffrey Lipman
Admin Inst: University of Queensland
Main RFCD: Intensive Care
Total funding: $612,859
Start Year: 2008
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
Antibiotic dosing in theAntibiotic dosing in the
Lay Description (from application):
The appropriate dosing of antibiotics for patient admitted to ICU after a traumatic injury is poorly defined and
based on intuition rather than evidence. Doctors need to predict which patients may develop very high
antibiotic clearances and dose accordingly so that potentially life-threatening infections do not occur. Given
these patients are unknown, this research seeks to identify such patients and recommend which antibiotic and
which dose is appropriate to ensure adequate treatment.
Research achievements (from final report):
This study has collected extensive physiological and pharmacokinetic data in critically ill patients and the work
will be cited frequently by major papers trying to understand why critically ill patients need different antibiotic
dosing approaches to other patient groups. Various publications in high impact factor journals have also been
made possible by this grant. The results of this project would be considered of landmark significance. The
potential benefits of this research are manifest initially in improved antibiotic treatment in patients with high
morbidity and mortality, that is critically ill patients with sepsis and with significant trauma. The other potential
benefits include industry partnerships to develop equipment and software to develop evidence based predictors
of antibiotic dosing for these 'at risk' patient groups. This translational work could also then be extended to
other difficult patients such as burns, febrile neutropenic patients.
Expected future outcomes:
Translational research that accurately predicts antibiotic dosing requirements for critically ill patients without
the need for therapeutic drug monitoring data to guide drug dosing.
Name of contact:
Prof Jeffrey Lipman
Email/Phone no. of contact:
j.lipman@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 519716
CIA Name: Prof John Fraser
Admin Inst: University of Queensland
Main RFCD: Systems Physiology
Total funding: $455,160
Start Year: 2008
End Year: 2010
Grant Type: NHMRC Project Grants
Title of research award:
Hyperpolarized Helium MRI to quantify regional lung damage and ventilation for improvement of recruitment
strategy.Hyperpolarized Helium MRI to quantify regional lung damage and ventilation for improvement of
recruitment strategy.
Lay Description (from application):
Many lung injuries need mechanical ventilation to reopen collapsed lung airspaces and supply oxygen to the
patient. This study uses two methods to monitor the lungs during ventilation: Hyperpolarised helium MRI to
image the airspace, and electrical impedance tomography to measure lung volume. This information will allow
adjustment of ventilator pressure to maximize oxygen transfer without increasing lung damage. Quicker repair
of lung damage and patient recovery are the benefits of this study.
Research achievements (from final report):
This grant has allowed the development and comparison of two techniques of imaging of the lung in ventilated
patients., , Hyperpolarised Helium MRI was successfully carried out in the rat using a high resolution MRI.
Whilst this is not the first time this has been done, our group is the only Australsian group who can do this, and
one of the few to have developed in house hyperpolarisation of helium combined with a custom designed
rodent ventilator allowing the maximum polarisation time to be achieved and all the 3He to be used in
imaging., , Electrical Impedance Tomography (EIT) was successfully undertaken in the same rats as
Hyperpolarised Helium MRI. We are the first group to perform EIT reliably in the rat and the first group to be
able to compare the two imaging techniques. This is of great significance as, while Hyperpolarised Helium
MRI can be seen as a "gold standard", it cannot be applied at the bedside or done frequently. Whereas, EIT is a
somewhat novel technique that can be done on a continuous basis at the bedside.
Expected future outcomes:
Three additional publications are under submission and review currently., , Sadly, the worldwide supply of
Helum 3 dramatically reduced during the course of this grant, which greatly restricted the number of studies
that could be performed. However, should Helium 3 become more readily available, we have identified how
this methodology could e used to optimise ventilation in the criticilly ill.
Name of contact:
John Fraser
John Fraser
Email/Phone no. of contact:
John_Fraser@health.qld.gov.au
NHMRC Research Achievements - SUMMARY
Grant ID: 519744
CIA Name: Dr Allison Pettit
Admin Inst: University of Queensland
Main RFCD: Orthopaedics
Total funding: $406,125
Start Year: 2008
End Year: 2013
Grant Type: Career Development Fellowships
Title of research award:
Osteal macrophages: novel regulators of osteoblast function and the endosteal stem cell nicheOsteal
macrophages: novel regulators of osteoblast function and the endosteal stem cell niche
Lay Description (from application):
Bone diseases are a major health problem and current treatments are inadequate. We are investigating a novel
role for macrophages (cells important in tissue maintenance and immune responses) in bone growth, repair and
disease. Greater understanding of this will provide new ways to treat bone disease. We will also determine if
these macrophages help support stem cells that reside near bone surfaces, which may provide new treatment
strategies to improve bone marrow transplantation in cancer.
Research achievements (from final report):
Bone and blood diseases are a substantial and increasing burdens on health systems and individuals. The
research undertaken during this Fellowship examined the symbiotic relationship between blood and bone. It
discovered that a specialized type of white blood cell, called osteal tissue macrophages or osteomacs for short,
plays an important role in: 1) maintenance of healing bone and aiding successful bone repair; and 2) generation
of specialized environments within bone marrow that house blood stem cells (cells responsible for repopulating
red and while blood cells throughout life). This suggests, and we are continuing to accumate data to support,
that alterations in the function of these osteomacs may contribute to bone diseases such as osteoporosis and
blood disease including anemia and leukemia. Importantly, the research showed that a treatment that increased
osteomacs was able to accelerate bone repair. Overall this research established that the osteomac plays an
important role in coordinating the functions of both the bone marrow and the bone in which is it housed. This
has important implications regarding the potential role of osteomacs in bone marrow transplantation, blood
cancers and tumours metastases that thrive in bone.
Expected future outcomes:
We will continue to accumulate pre-clinical data to support macrophage targeting therapies are a viable
approach to improving bone health, bone marrow transplantation outcomes and treatment approaches for bone
and blood cancer. This information will provide appropriate foundation for novel therapuetic design and drug
development for this broad range of medical conditions that have treatment gaps.
Name of contact:
Allison Pettit
Email/Phone no. of contact:
apettit@mmri.mater.org.au
NHMRC Research Achievements - SUMMARY
Grant ID: 519771
Start Year: 2008
CIA Name: Prof Michele Sterling
End Year: 2011
Admin Inst: University of Queensland
Grant Type: Career Development Fellowships
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $331,674
Title of research award:
Whiplash injury: Classification, prediction and directives for improved management strategies.Whiplash
injury: Classification, prediction and directives for improved management strategies.
Lay Description (from application):
Whiplash is a costly condition with many people developing chronic symptoms. This research aims to improve
the diagnosis and classification of the condition from the time of injury until either recovery or the
development of persistent pain. This will facilitate the early identification of those at risk of poor recovery and
will lay the foundations for the development of improved early management, particularly in primary care.
Research achievements (from final report):
This research has further developed and validated prognostic models for poor recovery following whiplash
injury allowing clinicians and stakeholders greater confidence in identifying people at high risk of developing
chronic pain and disability. It has also demonstrated the importance of psychological symptoms following the
injury, particularly symptoms of posttraumatic stress. Not only are these factors predictive of poor recovery but
they also show a relationship with physical features namely, morphological muscle change. The results of this
research demonstrate the clear importance of both physical and psychological aspects of this condition and that
they inter-relate. The research demonstrated that by addressing posttraumatic stress symptoms in people with
an already chronic condition, that pain, disability and distress were alleviated. The research has made a marked
impact on the field. The results have been included in current clinical practice guidelines and clinicians now
routinely evaluate patients for the presence of these factors. Treatment of Whiplash Associated Disorders is
changing as a result.
Expected future outcomes:
It is expcted that this research will pave the way for the development and testing of novel and new
interventions to prevent the development of chronic pain and disability following whiplash injury.
Name of contact:
Prof Michele Sterling
Email/Phone no. of contact:
m.sterling@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 519776
CIA Name: Prof Matthew Brown
Admin Inst: University of Queensland
Main RFCD: Geriatrics and Gerontology
Total funding: $810,661
Start Year: 2009
End Year: 2012
Grant Type: International Collaborations
Title of research award:
Genetic Factors for OsteoporosisGenetic Factors for Osteoporosis
Lay Description (from application):
Osteoporosis is a common condition in which bone strength is reduced due to reduced amount and quality of
bone. Reduced bone strength means an increased risk of fracture. Osteoporotic fractures occur in 1 in 2 women
and 1 in 3 men in their lifetime, and the likelihood of suffering osteoporotic fracture increases with age. Most
of the risk of developing osteoporosis is genetic, but few of the genes involved have been identified. Our goal
is to identify those genes. We will complete recruitment and assessment of a cohort of 1500 postmenopausal
women with either low or high bone mineral density from pre-existing population cohorts in Australia. A
genomewide association study will then be performed on these cases. Associated genes in different datasets
will then be investigated further in our cohort, and high-density SNP mapping performed to identify true
associated variants. These studies should identify most genetic variants associated with BMD variation and low
trauma fracture in the general community, allowing development of diagnostic-disease predictive genetic tests,
and informing development of novel therapeutic agents for osteoporosis.
Research achievements (from final report):
This funding enabled us to complete a genomewide association study of Australian, New Zealand and British
postmenopausal women with high or low bone mineral density. The data from this study was then tested in a
large cohort from the general population, and combined with data from other similar general population
cohorts. This lead to the identification of 56 novel loci associated with bone density and 14 loci associated with
fracture risk. The findings were published in a landmark report in the journal Nature Genetics in 2012 (see
below). These findings highlight new pathways that are involved in osteoporosis and osteoporotic fracture risk
and point to novel therapeutic targets. The potential of these findings in the identification of therapeutic targets
is highlighted by the fact that all bar one current osteoporosis treatment with a known mechanism of action
targets a gene identified by the genetic studies.
Expected future outcomes:
We have obtained further NHMRC funding to exome sequence the high and low bone mineral density cohort
to investigate less common genetic variants and their impact on osteoporosis risk. This study is ongoing both
within Australia and as part of the GEFOS consortium internationally.
Name of contact:
Matthew Brown
Email/Phone no. of contact:
matt.brown@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 519781
Start Year: 2008
CIA Name: Dr Shaun O'Leary
End Year: 2010
Admin Inst: University of Queensland
Grant Type: Early Career Fellowships (Australia)
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $117,229
Title of research award:
The classification of motor function impairment in chronic neck painThe classification of motor function
impairment in chronic neck pain
Lay Description (from application):
Disability due to painful neck disorders is a serious health issue. Changes in control of neck movement and
muscle function are known problems in neck pain sufferers yet management of these issues remains poorly
understood. This project aims to develop classifications that better identify movement and muscle problems in
the neck with the goal to facilitate better rehabilitation. This project is likely to significantly improve the
management of neck pain in the community.
Research achievements (from final report):
This research training fellowship has investigated muscle function in individuals with chronic neck pain. From
these studies we have demonstrated that individuals with neck pain have issues with the way they use their
muscles as well as changes in the physical conditioning of their muscles, particularly those with a whiplash
disorder. We have further shown that muscle dysfunction is linked to the severity of the symptoms a person is
experiencing. Of great clinical interest, we have shown that when you train muscles for the management of
neck pain, you will get a favourable reduction in pain from more than one type of exercise approach even
though the different exercise approaches will give very different outcomes in terms of muscle fitness.
Therefore, we now know that when managing a patient with neck pain, clinicians have some flexibility with
the approach they choose with regards to pain, but need to be very specific with regards to the patients muscle
fitness needs.
Expected future outcomes:
The findings from the work conducted in this fellowship has raised many additional questions. These questions
underpin our current series of studies all designed to answer the following question - How do I best manage
this patients neck pain?
Name of contact:
Shaun O'leary
Email/Phone no. of contact:
s.oleary@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 569660
Start Year: 2009
CIA Name: Prof Justin Kenardy
End Year: 2012
Admin Inst: University of Queensland
Grant Type: NHMRC Project Grants
Main RFCD: Health, Clinical and Counselling Psychology
Total funding: $359,112
Title of research award:
Comparison of cognitive-behavioural treatments for children with PTSD following an accidental injury: A
multi-site RCT.Comparison of cognitive-behavioural treatments for children with PTSD following an
accidental injury: A multi-site RCT.
Lay Description (from application):
Children who experience a traumatic event are at increased risk of developing Post traumatic stress disorder
(PTSD). Despite the significant consequences, and the poor prognosis of this disorder, few evaluations of
interventions for PTSD in children exist. This project will compare two active treatments (child vs. familyfocused cognitive behaviour therapy) for children experiencing PTSD following an accidental injury (the most
common category of traumatic events experienced by children).
Research achievements (from final report):
The study was designed to test an early intervention for children who have received a traumatic injury. The
study used a combination of "screen-and-treat" and "watchful waiting" models where all children presenting to
hospital were screened for their risk of developing posttraumatic stress disorder (PTSD) and then rescreened
after a waiting period. Within this study we tested the feasibility of a screening program for children and
adolescents exposed to traumatic injury and hospitalised in three Australian hospitals. 1,134 eligible families
were contacted and 546 children (48%) were screened for PTSD risk at 1-2 weeks post-injury. Of those
screened, 119 (21%) children were at-risk, 85 (15%) continued to screen at-risk at 4-6 weeks post-injury, 27
(4.95%) were diagnosed with PTSD and 22 (4%) received treatment. The screening program was successful at
identifying and reaching children with PTSD within 6 weeks of injury, however the response rate was lower
than expected which limited the overall feasibility of the screening program. The addition of a re-screening
phase, while reducing the number of participants progressing to treatment, demonstrated that not all high risk
children necessarily required intervention and highlighted the potential for re-screening as part of a watchful
waiting approach.
Expected future outcomes:
We expect to publish the final results of the study as well as the results of the screening procedure and the
outcomes of the low risk sample.
Name of contact:
Justin Kenardy
Email/Phone no. of contact:
j.kenardy@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 569666
Start Year: 2009
CIA Name: Prof David Pow
End Year: 2011
Admin Inst: University of Queensland
Grant Type: NHMRC Project Grants
Main RFCD: Neurosciences not elsewhere classified
Total funding: $526,878
Title of research award:
A novel marker of distressed neurons in the hypoxic brain: Regulation, function and potential clinical utility.A
novel marker of distressed neurons in the hypoxic brain: Regulation, function and potential clinical utility.
Lay Description (from application):
The brain is easily damaged by lack of oxygen (hypoxia). We have recently identified a novel protein called
GLAST1b which is expressed in distressed neurons. This protein is a glutamate transporter. Glutamate is
implicated as a toxic agent hypoxia. This study will investigate what regulates the expression of GLAST1b,
what the consequences of expression are, and whether this marker can be developed as a diagnostic tool for
identifying the presence of, and distribution of brain damage.
Research achievements (from final report):
This project investigated the idea that novel forms of a class of protein called glutamate transporters were
effective markers of distressed neurons in the brain. This study confirmed this in animal models and in human
brains. During this study we needed to examine the morphology of the astrocytes surrounding the stressed
neurons, and we accomplished this with associated papers being published. We also examined the testis as it
has properties like the brain (it has a blood testis barrier) and this gave us new leads into transporter splicing in
the brain. We also found an entirely new and abundant form of the glutaate transporter GLAST during these
studies. We have discovered changes in expression of new forms of the transporters we have investigated in the
human brain. Perhaps most excitingly we discovered novel forms of a protein called EAAT5 in brain which
may be the key regulators of excitability in the brain and a new NHMRC grant application has been submitted
to study them., , ,
Expected future outcomes:
The application has identified the key ways that alternate splicing of glutamate transportes may contribute to
brain disease, and in doing so has identified new forms of these critical proteins. They are now the subject of
ongoing investigatons and new grant applications.
Name of contact:
David Pow
Email/Phone no. of contact:
david.pow@rmit.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 569744
Start Year: 2009
CIA Name: Prof Paul Hodges
End Year: 2012
Admin Inst: University of Queensland
Grant Type: NHMRC Project Grants
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $417,882
Title of research award:
Reconsideration of the motor adaptation to painReconsideration of the motor adaptation to pain
Lay Description (from application):
Pain changes movement. Although undisputed, there is a surprising lack of agreement regarding the underlying
mechanisms. This project involves an innovative mix of neurophysiological methods to investigate the drive to
muscle cells from the nervous system and changes in the mechanics of contraction. These studies will resolve
the perplexing problem of how pain changes our ability to activate muscle. Clear understanding of the
underlying mechanisms can guide rehabilitation.
Research achievements (from final report):
We aimed to explore a new theory to explain movement changes in pain. It was our contention that exploration
of movement control at the micro level (motoneuron discharge/muscle fibre activation) would provide
important insight, and ultimately provide new directions for development of rehabilitation techniques for
people with pain. The work formed the basis for 2 keynote lectures, 2 invited reviews, 12 conferences
presentations and published 4 journal articles., We showed that: 1) the population of muscle fibres used to
produce force changes during pain; 2) this change is observed across a range of muscles and contraction types;
3) similar changes in muscle fibre activation occur when pain is induced in muscular and non-muscular tissue,
4) similar changes occur when the pain is anticipated but not present; 5) Pain increases the synchronisation of
motor unit activity (that is, the liklihood that multiple muscle fibres contract at the same time) within a muscle
and decreases synchronisation between muscles; 6) Changes in muscle fibre activation during pain are
associated with a change in the direction/angle that force is produced; 7) Both distribution of muscle activity
and direction of force produced are independent of pain location and 8) The activation of the muscle during
pain appears to preferentially target larger muscle fibres (those that generate greater force) rather than the
smaller muscle fibres (that are used for more precision tasks) during pain. All of these changes help explain
how movement is changed in pain and some of the potentially problematic outcomes of these changes.
Expected future outcomes:
One manuscript is submitted, 3 manuscripts are in final stages of preparation. This work has established
fundamentals of movement adaptation and provided the basis for ongoing work that includes tasks with
increased complexity, during sustained pain. We aim to bridge-the-gap between studies of acute experimental
pain and clinical pain conditions.
Name of contact:
Dr Kylie Tucker
Email/Phone no. of contact:
k.tucker1@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 569807
CIA Name: A/Pr Emma Duncan
Admin Inst: University of Queensland
Main RFCD: Genetics not elsewhere classified
Total funding: $107,366
Start Year: 2009
End Year: 2010
Grant Type: Career Development Fellowships
Title of research award:
Genetic Determinants of Bone MassGenetic Determinants of Bone Mass
Lay Description (from application):
I am a clinician-scientist and endocrinologist most interested in clinical problems associated with bone, in
particular the highly heritable disease of osteoporosis. I hope by studying genetic determinants of bone mass to
determine the key genes involved, with the long term aim of informing the development of novel therapies for
this common, painful and disabling disease.
Research achievements (from final report):
I was awarded this grant to investigate the genetics of osteoporosis, through genome-wide association studies
and investigation of unusual bone phenotypes such as high bone mass and skeletal dysplasias. In the course of
the last two years, I have finished in entirity a genome-wide assoication study (GWAS) in extremes of bone
mass (published in PLoS Genetics), finding new genes associated with osteoporosis and confirming many
others. In individuals and families with high bone mass, I searched for the genetic cause with both conventional
and next generation sequencing, and linkage and association studies. I established a genetics programme in
patients and families with skeletal dysplasia (with a further publication in PLoS Genetics). I have also
published a clinical paper in management of osteogenesis imperfecta; two pharmacoepidemiological studies;
and two invited reviews of osteoporosis genetics and future strategies for gene mapping. All these studies aim
to unravel the genetic determination of bone mass, so that this can be translated into new treatment approaches
for management of common bone diseases, such as osteoporosis.
Expected future outcomes:
These projects have already demonstrated new genes and pathways determining bone mass, increasing our
understanding of what causes bone diseases such as osteoporosis. This then raises new possibilities for
different therapeutic approaches for common and devastating bone diseases such as osteoporosis.
Name of contact:
Emma Duncan
Email/Phone no. of contact:
e.duncan@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 569826
Start Year: 2009
CIA Name: Dr Stella Bjorkman
End Year: 2011
Admin Inst: University of Queensland
Grant Type: NHMRC Project Grants
Main RFCD: Neurology and Neuromuscular Diseases
Total funding: $547,971
Title of research award:
GABA excitotoxicity, neuroprotection and the perinatal brainGABA excitotoxicity, neuroprotection and the
perinatal brain
Lay Description (from application):
Approximately 3.5% of babies die each year from brain damage due to perinatal asphyxia, a shortage of
oxygen to the developing brain. Babies that survive face lifelong neurological disabilities, placing enormous
burden on health, social and economic resources. Current treatments are inadequate. We will examine what
occurs when there is a shortage of oxygen to the developing brain and investigate pathways to hypoxic brain
injury that offer opportunities for therapeutic intervention.
Research achievements (from final report):
We established the normal developmental profile of the GABAA receptor a1, a3, b2 and NKCC1 and KCC2
proteins in 4 cortical regions and hippocampus from piglet across several gestational timepoints. We have
demonstrated a switch in expression between the a3 and a1 proteins around birth which is similar to that
previously reported in other species and, a coincident upregualtion of KCC2 expression which togther may
constitute the maturation of inhibitory function of the GABAA receptor. we also showed that this switch was
regionally and temporally dependant. NKCC1 was found to be stably expresssed across gestation in the piglet
brain. The effect of HI on GABAA receptor a1, a3 and NKCC1 and KCC2 proteins resulted in significant
decreases in expression that was further exacerbated by the presence of seizures. Establishing the normal
developmental profile of these systems and understanding the effect of seizures on these proteins will allow us
to better direct future research on antiepileptic treatments specific and appropriate for the developing newborn
brain. The GABA system may also offer another potential avenue for neuroptotection following HI injury.
Expected future outcomes:
Results from this study have provided insights as to the excitotoxic role of the GABA system in newborn HI
brain injury and have laid the foundation for pursuing alterantive pathways to neuroprotection and treatment of
seizures.
Name of contact:
Dr Tracey Bjorkman
Email/Phone no. of contact:
t.bjorkman@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 569829
CIA Name: Prof Matthew Brown
Admin Inst: University of Queensland
Main RFCD: Immunogenetics
Total funding: $568,612
Start Year: 2009
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
Major Histocompatibility Complex (MHC) Genetics of Ankylosing SpondylitisMajor Histocompatibility
Complex (MHC) Genetics of Ankylosing Spondylitis
Lay Description (from application):
Ankylosing spondylitis (AS) is the prototypic condition of a group of types of inflammatory arthritis called
'seronegative spondyloarthropathies'. These conditions are the most common form of inflammatory arthritis in
white populations and occur worldwide. One third of the risk of developing AS is determined by genes within
a region called the 'major histocompatibility complex' (MHC), in addition to the gene HLA-B27, the main gene
causing AS. We aim to identify the remaining MHC genes.
Research achievements (from final report):
o
The identification of an HLA-B27
tagSNP, rs4349859, which acts as a nearly perfect surrogate of HLA-B27 (within the level of HLA-B27
genotyping accuracy). This SNP can be genotyped for <1% of the cost of current HLA-B27 typing methods; as
HLA-B27 typing is one of the most widely used genetic screening tests performed worldwide, this will have a
major impact on reducing costs. A patent application has been lodged regarding this finding (Australian
Provisional Patent Application No. 2009905817)., o
Using this finding, we demonstrated
that there were no other common variants with significant MHC associations in AS. This was published in
Nature Genetics (P001085096)., o
We used this finding to investigate
differences between HLA-B27 positive and -negative disease, thereby identifying the restriction of the
association of ERAP1 with AS, the first confirmed example of gene-gene interaction in any common human
disease. This was published in Nature Genetics (P001085096). The finding is of major importance in AS
research as it indicates that the mechanism by which HLA-B27 induces AS must involve aberrant peptide
handling, with increased presentation of peptides by ERAP1 to HLA-B27 increasing the risk of disease. This
narrows the potential mechanisms by which HLA-B27 induces AS substantially., o
Having
identified that interaction, we hypothesized and then confirmed that HLA-Cw6 interacted with ERAP1 in a
similar way. This was published in Nature Genetics (P000790258). This indicates that HLA-Cw6 likely
operates in psoriasis by a similar mechanism to which HLA-B27 operates in AS.
Expected future outcomes:
This will enable cheap population screening for AS, and inform development of AS and psoriasis therapies.
Name of contact:
Matthew Brown
Email/Phone no. of contact:
matt.brown@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 569830
CIA Name: Prof Matthew Brown
Admin Inst: University of Queensland
Main RFCD: Immunogenetics
Total funding: $536,680
Start Year: 2009
End Year: 2011
Grant Type: NHMRC Project Grants
Title of research award:
The immunogenetics of ankylosing spondylitis: a genetic and functional investigation of IL23R and related
genesThe immunogenetics of ankylosing spondylitis: a genetic and functional investigation of IL23R and
related genes
Lay Description (from application):
Ankylosing spondylitis (AS) is a common inflammatory arthritis which causes primarily back pain and
stiffness, and affects 1/250 individuals. Our group identified association between tagging genetic markers in
the gene IL23R and AS, and our preliminary data suggests some related genes are involved as well. This study
aims to identify the key genetic variants involved and determine the mechanism by which they cause AS.
Research achievements (from final report):
Ankylosing spondylitis (AS) is a common form of inflammatory arthritis affecting over 20,000 Australians
with an annual cost upto $500 million which targets the spine and pelvis. In a major breakthrough we
demonstrated that mutations in the gene IL23R were associated with AS. IL-23R is a key factor in the
regulation of the proinflammatory cytokine IL-17 which is thought to play a role in a number of inflammatory
diseases. The exact mechanism underlying the association between IL23R and AS is unknown so this grant
undertook to elucidate those mechanisms., To date IL23R has only been associated with AS in white European
patients. To establish that IL23R plays a role in different ethnic populations that also suffer from AS we looked
in Han Chinese which suffer similarly to white Europeans from AS. Although the same IL23R mutations did
not play a role in white Europeans as in Han Chinese, we discovered different mutations in IL23R in Han
Chinese associated with AS further emphasising the importance of the IL23 pathway in AS., We also looked at
the functional role of IL23R in AS. We looked at immune cells from AS patients and controls and investigated
whether there were differences in the cells that utilise IL23 signalling. We discovered that there is a subset of
immune cells that are more responsive to IL23 and produce more IL17 that are more prevalent in AS patients.
These cells were IL23R+ IL17+ gamma delta T cells and we hypothesise these play a key role in AS.
Expected future outcomes:
Confirming a role for the IL23R pathway in non-Caucasian populations further supports development of
therapeutics based on targeting IL23 signalling
Name of contact:
Dr Gethin Thomas
Email/Phone no. of contact:
gethin.thomas@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 569832
Start Year: 2009
CIA Name: Prof Michele Sterling
End Year: 2012
Admin Inst: University of Queensland
Grant Type: NHMRC Project Grants
Main RFCD: Complementary-Alternative Medicine not elsewhere classified
Total funding: $309,340
Title of research award:
Combined dry-needling, advice and graded exercise: a randomized controlled trial in chronic
whiplashCombined dry-needling, advice and graded exercise: a randomized controlled trial in chronic whiplash
Lay Description (from application):
Central hyperexcitability is a feature of chronic whiplash and may be one reason for the poor response of this
condition to standard treatment approaches such as exercise. Complementary and Alternative Medicine (CAM)
treatment of dry-needling has shown potential to decrease this hypersensitivity in other musculoskeletal
conditions. This study will investigate the effects of dry-needling combined with an orthodox treatment of
advice and graded exercise on pain and disability in chronic whiplash.
Research achievements (from final report):
The primary aim of this project was to investigate the effectiveness and cost effectiveness of combined dryneedling, advice and exercise for chronic whiplash. The results of the study demonstrated that both
interventions (dry-needling and exercise; sham needling and exercise) resultsed in clinically significant
chnages in all main outcome measures of pain and disability. However neither intervention was superior to the
other. The results would tend to suggest that the exercise component is the effective part of the intervention,
however our effect sizes are much larger than other trials using exercise only. Thus it is possible that an undefined mechanisms of dry-needling or sham -dry-needling that stimulates only the skin may add an additional
effect compared to exercise also. The results are significant as few treatments have been shown to be clnically
effective for chronic whiplash associated disorders (WAD).
Expected future outcomes:
The results of the trial will be included in the training of physiotherapists and others in their management of
WAD. Further analysis of results will be undertaken inorder to generate future hypotheses for the effects of
dry-needling and to guage responders and non-reponders of theis approach to treatment.
Name of contact:
Prof Michele Sterling
Email/Phone no. of contact:
m.sterling@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 569855
Start Year: 2009
CIA Name: Prof Istvan Toth
End Year: 2010
Admin Inst: University of Queensland
Grant Type: NHMRC Development Grants
Main RFCD: Pharmaceutical Sciences and Pharmacy
Total funding: $209,471
Title of research award:
Neuropathic pain drugs based on the endogenous opioid peptide Endomorphin 1.Neuropathic pain drugs based
on the endogenous opioid peptide Endomorphin 1.
Lay Description (from application):
We have developed a new pain drug based on the natural pain killing opioid peptide, Endomorhin 1. The new
drug exhibits activity similar to morphine and gabapentin against neuropathic pain in animals but seems to act
through a different mechanism. We will complete our preclinical investigation of this compound by assessing
its side effect profile and tolerance inducing properties in animals. We will also continue our development of
an orally active analogue of this important peptide
Research achievements (from final report):
Neuropathic pain is a condition associated with nerve damage and is a common complication of diabetes,
musculoskeletal injury, and cancer. The treatment of neuropathic pain is a major unmet medical need.
Currently, opioid drugs are used to treat neuropathic pain, but result in a range of side effects, particularly
tolerance, respiratory depression, and constipation. Endomorphin-1, an endogenous opioid peptide, has the
potential to treat neuropathic pain but is unsuitable for clinical application due to poor metabolic stability and
poor oral absorption in its native form. , We created a range of derivatives aimed at improving the drug-like
properties of Endomorphin-1. These derivatives were screened in vitro to determine the μ-opioid receptor
binding and agonist activity. Promising candidates progressed to in vivo screening in a rat chronic constriction
injury model of neuropathic pain. The results of in vivo testing identified Endomorphin-1 derivatives with
dose-dependent activity when delivered intravenously. Oral analgesic potential was also evaluated and was
comparable to that of morphine. Less tolerance developed to the analgesic effect of the lead Endomorphin-1
derivative than morphine at equipotent doses. The Endomorphin-1 derivative produced less side effects
(respiratory depression, constipation, tolerance) than morphine at antinoiciceptive doses. , Our findings suggest
that Endomorphin-1 derivatives have the potential to be developed as novel opioid analgesic agenst to treat
neuropathic pain with a wider therapeutic window in respect to constipation and respiratory depression. Further
development of the lead Endomorhpin-1 derivative may result in the production of a clinical therapeutic for
neuropathic pain.
Expected future outcomes:
After completion of further preclinical examinations we will pursue business partners to progress to clinical
trials.
Name of contact:
Prof Istvan Toth
Email/Phone no. of contact:
i.toth@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 631363
CIA Name: Dr Gethin Thomas
Admin Inst: University of Queensland
Main RFCD: Genomics
Total funding: $431,201
Start Year: 2010
End Year: 2013
Grant Type: NHMRC Project Grants
Title of research award:
Regulatory RNAs Underlying Genetic Associations With Ankylosing SpondylitisRegulatory RNAs Underlying
Genetic Associations With Ankylosing Spondylitis
Lay Description (from application):
Ankylosing spondylitis is a chronic inflammatory disease affecting the spine and causing back pain. The
diagnosis of the disease is delayed by up to 10 years due to lack of accurate tests. We aim to identify molecular
signatures of the disease that might be used to distinguish inflammatory processes typical of the disease and
other causes of back pain. This would allow earlier and more accurate diagnosis of the disease and result earlier
patient treatment and better health outcomes.
Research achievements (from final report):
Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting the spine and causing back pain. The
diagnosis of the disease is delayed by up to 10 years due to lack of accurate tests. We aim to identify molecular
signatures of the disease that might be used to distinguish inflammatory processes typical of the disease and
other causes of back pain. This would allow identification of novel molecules and mechanisms controlling
disease which can lead to new therapeutic approaches and also earlier and more accurate diagnosis of the
disease and result earlier patient treatment and better health outcomes., We have identified a novel molecule
that is produced from a genetic region previously associated with ankylosing spondylitis. This region was
termed a "gene desert" due to the fact that no known genes that might mediate disease were identified in this
region. Using cutting edge next-generation RNA sequencing technology we comprehensively identified all
forms of RNA produced from this region. From these studies we have identified a novel RNA that is highly
expressed in immune cells and is overexpressed in AS patients. This novel RNA may identify a new regulatory
pathway in AS.
Expected future outcomes:
This novel transcript will likely be part of a novel pathway regulating development or severity of AS. We will
now undertake further studies characterising the mode of action of this RNA and identify new therapeutic dn
diagnostic targets.
Name of contact:
Gethin Thomas
Email/Phone no. of contact:
gethin.thomas@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 631451
Start Year: 2010
CIA Name: Dr Karin Borges
End Year: 2012
Admin Inst: University of Queensland
Grant Type: NHMRC Project Grants
Main RFCD: Neurology and Neuromuscular Diseases
Total funding: $314,717
Title of research award:
Complement activation in experimental epilepsy: role of C5a receptorsComplement activation in experimental
epilepsy: role of C5a receptors
Lay Description (from application):
400,000 patients in Australia suffer from epilepsy and 45% of them suffer from uncontrolled seizures. Epilepsy
often develops after head injury or stroke, but no treatments are available to prevent this process. Inflammatory
processes seem to be involved in epilepsy. We will investigate if the inflammatory complement factor C5a
plays a role in epilepsy and if we can prevent development of seizures in mice. If successful our data will be a
prerequisite for later clinical trials.
Research achievements (from final report):
At least 50 million people worldwide and 200,000 patients in Australia suffer from epilepsy. Despite drug
treatment, about 45% of patients still experience seizures. Even the development of newer better tolerated
drugs in the last 15 years has not increased the efficacy of treatment. Therefore new approaches are urgently
needed to find new effective treatments for epilepsy patients. The goal of this research was to define new
treatment targets. There is now increasing evidence that inflammatory processes are involved in epilepsy. We
discovered that an experimental anti-inflammatory compound effectively inhibited seizures in several mouse
models. The drug appears to act via a protein that is well known in the complement inflammation pathway.
Because the substance is only short-lived once it enters the body, it is now important to develop similar
compounds with improved stability that then may be tested in clinical trials in the near future. Also, we will
need to very that the target protein is found in epileptic brain areas in patients. This will be achieved within the
next year by testing samples obtained from human epilepsy surgeries. In summary this research grant paved the
way towards the discovery of a new approach to treat seizures.
Expected future outcomes:
There is a good chance that the inflammatory protein is found in human epileptic brain areas. We hope that
new stable compounds that are safe and non-toxic and target this protein can be found and trialled in humans
soon.
Name of contact:
Karin Borges
Email/Phone no. of contact:
k.borges@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 631484
CIA Name: Dr Allison Pettit
Admin Inst: University of Queensland
Main RFCD: Orthopaedics
Total funding: $741,095
Start Year: 2010
End Year: 2013
Grant Type: NHMRC Project Grants
Title of research award:
Regulation of Bone Dynamics by Osteal Tissue Macrophages (Osteomacs)Regulation of Bone Dynamics by
Osteal Tissue Macrophages (Osteomacs)
Lay Description (from application):
There is a high demand for effective treatments to rebuild and replace lost bone in fracture repair and
osteoporosis. We have described a discrete population of macrophages (classically immune defense cells)
within the specialized tissues that line bones. We have shown that these bone tissue macrophages have a novel
role in promoting the formation of new bone. This project grant will extend these observations and identify the
clinical potential of bone tissue macrophages to treat bone disease.
Research achievements (from final report):
Bone disease and fracture are a substantial and increasing burden on health systems and individuals. There is
clinical need for better therapies that rebuild bones and overcome compromised fracture repair. The research
undertaken during this grant expanded on our earlier discovery demonstrating the bone supportive functions of
a particular type of white blood cells, called osteal tissue macrophages or osteomacs for short. We showed that
osteomacs are required for bones to repair after fracture healing irrespective mode of healing (bones can heal
by 2 different mechanisms). Most importantly, a treatment that increased osteomacs was able to accelerate
bone repair. This provides proof-of-principle that enhancing the function of these cells is a viable treatment
approach for improving fracture outcomes. We generated data showing the osteomacs achieve this function
through influencing the maturation and/or function of the cells that make bone as well as the cells that degrade
bone. During the funding period the research rapidly evolved to demonstrate that osteomacs also play an
integral role in creating the specialized environments within bone marrow that house blood stem cells (cells
responsible for repopulating red and while blood cells throughout life). Overall we establish that the osteomac
plays an important role in coordinating the functions of both the bone marrow and the bone in which is it
housed. This has important implications regarding the potential role of osteomacs in bone marrow
transplantation, blood cancers and tumours metastases that thrive in bone.
Expected future outcomes:
We will continue to accumulate pre-clinical data to support macrophage targeting therapies are a viable
approach to improving bone health, bone marrow transplantation outcomes and treatment approaches for bone
and blood cancer. This information will provide appropriate foundation for novel therapuetic design and drug
development for this broad range of medical conditions that have treatment gaps.
Name of contact:
Allison Pettit
Email/Phone no. of contact:
apettit@mmri.mater.org.au
NHMRC Research Achievements - SUMMARY
Grant ID: 631532
CIA Name: Prof Geoffrey Goodhill
Admin Inst: University of Queensland
Main RFCD: Cellular Nervous System
Total funding: $527,339
Start Year: 2010
End Year: 2012
Grant Type: NHMRC Project Grants
Title of research award:
Cyclic-nucleotide-dependent regulation of axon guidance sensitivityCyclic-nucleotide-dependent regulation of
axon guidance sensitivity
Lay Description (from application):
Problems in wiring up the brain underlie several nervous system disorders. The goal of this project is to
understand better how this wiring normally forms. This will ultimately lead to a better understanding of what
can go wrong with brain wiring, and how to fix such problems. It will also lead to a better understanding of
how to make axons regenerate after injury.
Research achievements (from final report):
For the brain to function correctly its neurons must be connected correctly. Developing nerve fibres find their
correct targets during neural development by detecting chemical guidance cues in the brain, particularly
chemical gradients. However whether they are attracted or repelled by these gradients depends on the overall
levels of certain other chemicals, particularly cAMP. Understanding how this process works is important not
just for understanding how normal brain development could go wrong, but also how to encourage nerve fibres
to regrow appropriately after injury. In this project we used a unique combination of experiments and
mathematical modelling to understand the mechanisms by which cAMP modulates guidance responses. Our
key finding was that levels of cAMP interact with levels of calcium, and that both of these levels must be
tightly regulated to ensure that nerve fibres are not attracted when they're supposed to be repelled, and vice
versa.
Expected future outcomes:
This work provides a predictive tool that can be used to understand how nerve fibres will behave under
different circumstances, and also provides a mathematical framework within which to investigate other aspects
of how intracellular signalling pathways control the direction of nerve fibre growth.
Name of contact:
Prof Geoffrey Goodhill
Email/Phone no. of contact:
g.goodhill@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 631598
CIA Name: Prof Brian Key
Admin Inst: University of Queensland
Main RFCD: Cellular Nervous System
Total funding: $586,428
Start Year: 2010
End Year: 2012
Grant Type: NHMRC Project Grants
Title of research award:
Molecular and cellular mechanisms of vertebrate brain developmentMolecular and cellular mechanisms of
vertebrate brain development
Lay Description (from application):
The essential steps in forming a normal functioning brain occur during life as an embryo. If these processes go
haywire, there can be serious repercussions for life after birth. This project seeks to understand how the brain
forms during embryonic stages so that better treatments and procedures can be developed to deal with
developmental problems.
Research achievements (from final report):
The essential steps in forming a normal functioning brain occur during life as an embryo. If these processes go
haywire, there can be serious repercussions for life after birth. This project sought to understand how the brain
forms during embryonic stages so that better treatments and procedures can be developed to deal with
developmental problems. A network of genes associated with maintinaing the adhesiveness of cells in the
embryonic nervous systems were found for the first time to play a critical role in the normal formation of the
brain. The results provide the framework for understanding why mutations in such genes could lead to birth
defects associated with brain.
Expected future outcomes:
Neural tube defects such as spina bifurda involve lesions of the spinal cord which can have severe functional
consequences. The results of this project provide the foundation for better understanding the genetics of spina
bifurda.
Name of contact:
Brian Key
Email/Phone no. of contact:
brian.key@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 631629
Start Year: 2010
CIA Name: Prof Justin Cooper-White
End Year: 2011
Admin Inst: University of Queensland
Grant Type: NHMRC Project Grants
Main RFCD: Regenerative Medicine (incl. Stem Cells and Tissue Engineering)
Total funding: $296,867
Title of research award:
TAKING THE LIMP OUT OF CARTILAGE REPAIRTAKING THE LIMP OUT OF CARTILAGE REPAIR
Lay Description (from application):
In Australia osteoarthritis is the leading cause of pain and disability with the majority of individuals displaying
radiographic evidence of this condition by age 65. We are developing two novel technologies which use
patients' own stem cells to repair damaged cartilage. This project involves both the advancement of these
technologies as well as their evaluation using a sheep cartilage repair model. These technologies offer
significant promise for those suffering joint pain.
Research achievements (from final report):
, This project aimed to produce highly functional cartilage cells (chondrocytes) from mesenchymal stem cells
(MSCs) using our novel low oxygen micropellet (LOM) differentiation process and a novel in vitro culture
system, which prevents matrix loss to the bulk medium, to generate fully functional ex vivo cartilage tissue
plugs. We have successfully demonstrated that LOMs can be readily assembled into larger tissue constructs
suitable for cartilage defect repair. Further, we have optimized MSC chondro-induction medium, to enhance
early chondrogenic differentiation, and subsequently enhance the matrix output of mature cells. The effects of
the presence/presentation of extracellular matrix (ECM) molecules on the conversation of MSCs to
chondrocytes have been thoroughly investgated and these insights have been translated to the formulation
design of novel hydrogel scaffolds. This scaffold system is capable of displaying ECM molecules and can be
optimised to match cartilage tissue mechanics. MSCs have been successfully encapsulated within the hydrogels
and cultured under inductive conditions. These outputs confirm the utility of our novel in vitro protocols for
functional cartilage tissue formation, in readiness for in vivo assessment.
Expected future outcomes:
, The ultimate aim of our work into cartilage tissue engineering is to generate functional ex vivo cartilage tissue
from MSCs and test its suitability for cartilage repair in humans. The results obtained from this in vitro
investigation have provided the necessary proof-of-concept data to permit this novel approach to move into in
vivo assessment within appropriate small animal models.
Name of contact:
Justin Cooper-White
Email/Phone no. of contact:
j.cooperwhite@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 631634
CIA Name: Dr Massimo Hilliard
Admin Inst: University of Queensland
Main RFCD: Cellular Nervous System
Total funding: $461,598
Start Year: 2010
End Year: 2012
Grant Type: NHMRC Project Grants
Title of research award:
Membrane fusion in axonal regeneration: molecules and mechanismsMembrane fusion in axonal regeneration:
molecules and mechanisms
Lay Description (from application):
Limited nerve regeneration is the main obstacle for recovery from spinal cord and brain injuries. Understanding
the cellular and molecular mechanisms underlying axonal regeneration is an essential step toward the
development of novel effective therapies to enhance this process. In this proposal, we use the powerful
molecular and genetic tools available for the small nematode worm C. elegans to identify and study axonal
regeneration and discover the key molecules involved.
Research achievements (from final report):
We focused our research on nerve repair using the mechanosensory neurons of the nematode worm C. elegans
as a model system. By generating nerve transection with a laser microbeam, we have discovered that the two
separated halves of a C. elegans nerve are able to reconnect and re-establish the original tract. We also revealed
that this is a highly efficient process, with an injured nerve able to reconnect selectively with its own separated
half and not with other injured nerves in the vicinity. Using a genetic approach, we identified some of the key
molecules and mechanisms necessary for this nerve repair to occur. Given the high level of conservation of
these molecules with those present in humans, we hope that our discoveries can soon be exploited to develop
novel and more effective therapies to treat injuries of the nervous system.
Expected future outcomes:
Understanding the molecular mechanisms of nerve regeneration is a crucial step to develop novel therapies to
favour repair and treat injuries to the nervous system. Our studies in the nematode C. elegans have revealed
several new molecules that could be exploited to facilitate nerve repair in higher organisms.
Name of contact:
Massimo A. Hilliard
Email/Phone no. of contact:
m.hilliard@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 1017308
Start Year: 2011
CIA Name: Prof Perry Bartlett
End Year: 2014
Admin Inst: University of Queensland
Grant Type: NHMRC Development Grants
Main RFCD: Neurology and Neuromuscular Diseases
Total funding: $687,106
Title of research award:
Therapeutic development of a novel EphA4 antagonist for spinal cord injuriesTherapeutic development of a
novel EphA4 antagonist for spinal cord injuries
Lay Description (from application):
Spinal cord injuries impose a significant burden on patients and their carers. At present, there are no treatments
for spinal cord injury that provide functional improvement. This research program will develop a novel
therapeutic molecule, EphA4-Fc, which promotes axonal regeneration and delivers significant functional
improvement. We will determine the most effective protocol for EphA4-Fc administration and the
physiological and functional outcomes of these treatment regimes.
Research achievements (from final report):
Sufferers of spinal cord injury often experience permanent deficits in movement and sensation, which is due to
the inability of the human nervous system to repair itself. More than 10 years ago, the CIs, Professor Perry
Bartlett and Professor Andrew Boyd, discovered that the EphA4 protein inhibits the regeneration of nerve cells
following acute injury. Since this time, as part of the work funded by this grant, the CIs have investigated a
number of ways by which to block the action of this protein in an effort to allow the nerve cells to regenerate
across and around the site of injury. By conducting a large dose-response study in a rat model of contusive
spinal cord injury, the team has shown that treatment with a competitive protein (EphA4-Fc), which prevents
EphA4 from binding to its receptor and acting as an inhibitory agent, results in improvements in locomotion. In
addition to improved movement, the animals were found to have accelerated weight recovery and superior
balance and coordination. Changes in tissue structure around the injury site were also observed in EphA4-Fctreated animals. Overall, the use of EphA4-Fc following spinal cord injury has been shown to result in
improved functional and structural outcomes, and the CIs have uncovered more about the mechanism by which
EphA4 regulates axonal regeneration. These findings hold great promise for those with spinal cord injury, as
treatment with the competitive antagonist EphA4-Fc following injury may allow some degree of axonal repair
and thus improved functional outcomes.
Expected future outcomes:
Given the significant functional improvements seen in animal models following treatment with the EphA4-Fc
protein, the CIs are in talks with industry to prepare the protein for a Phase 1 clinical trial.
Name of contact:
Mikaeli Costello
Email/Phone no. of contact:
mikaeli.costello@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 453442
CIA Name: A/Pr Cory Xian
Admin Inst: University of South Australia
Main RFCD: Orthopaedics
Total funding: $366,302
Start Year: 2007
End Year: 2009
Grant Type: NHMRC Project Grants
Title of research award:
Roles of injury-induced inflammatory response in regulating bony repair at injured growth plate cartilageRoles
of injury-induced inflammatory response in regulating bony repair at injured growth plate cartilage
Lay Description (from application):
Children's growth plate cartilage is responsible for bone lengthening. Due to popularity of sports and play,
trauma-induced growth plate damage and subsequently bone growth defects are common in children, with up
to 30% of growth plate injury cases resulting in growth abnormality, for which the present surgical correction
is highly invasive and not fully effective. Although we know that the growth plate injury-induced bone growth
defects result from bony repair of the injured growth cartilage, we largely don't understand why and how this
bony repair occurs. Understanding mechanisms for this "faulty" bony repair of injured growth plate will be
critical prior to effective biological treatments can be developed. Recently, using an injury model in young rats,
we found that bony tissue formation at injured growth plate is preceded sequentially by inflammatory,
fibrogenic, chondrogenic and osteogenic responses. The inflammatory response is an initial event and our
recent studies suggest that inflammatory response recruits inflammatory cells and produces important
molecules that could significantly influence subsequent fibrogenic, chondrogenic and osteogenic events leading
to the bony repair of the injured growth plate cartilage. The current proposal further addresses roles of the
inflammatory response and the molecular pathways of this response in regulating downstream bony repair
events. This project will generate novel understanding on the "faulty" bony repair of injured growth plate, and
will provide valuable information for developing cost-effective and simple therapeutic intervention that aims to
prevent bony repair and to enhance cartilage regeneration of the injured growth plate in children.
Research achievements (from final report):
Growth plate injuries are common and are often repaired by bony tissue which causes limb length
discrepancy/angulations. In past 3 years, using a rat model, we have confirmed 4 phases of injury responses
(inflammatory, fibrogenic, chondrogenic/osteogenic, and bone bridge formation/maturation) and involvement
of intramembranous and endochondral ossification mechanisms in the bony repair. Our global gene expression
(microarray) analysis revealed altered Wnt and BMP signalling pathways during growth plate bony repair. We
observed that some cytokines and growth factors were upregulated during the inflammatory phase, and that
infiltrated marrow stromal progenitor cells are responsive to PDGF and TNF-a in migration; to PDGF, TGF-a,
FGF-2, and TNF-a in proliferation; and to TGF-b1 and BMP in chondrogenesis. We have shown that inhibition
of osteogenic transcription factor Osx by blocking PKD activation appears to suppress bony repair and enhance
cartilage repair at the injury site. Using a sheep model, we demonstrated that ovine bone marrow mesenchymal
stem cells (MSC) are multipotential and can form cartilage-like tissue when transplanted etopically in mice,
and that in a growth plate injury model in lambs, autologous marrow MSC failed to promote growth plate
cartilage regeneration. Summary: In the last 3 years with this grant, we have achieved a good understanding of
the mechanisms for the "faulty" bony repair of injured growth plate, and have identified some potential targets
(eg, infiltration of stromal progenitors prior to bony repair) for investigating potential biological strategies for
preventing the faulty bony repair and promote cartilage regeneration of the injured growth plate.
Expected future outcomes:
Further increased understanding of the pathophysiology for the growth plate faulty repair will be achieved from
follow-up studies. Further studies will be carried out to investigate therapeutic potential of ex vivo expanded
autologous MSC in promoting growth plate regeneration, and to explore strategies to enhance growth plate
regeneration by mobilising endogenous MSC.
Name of contact:
Prof Cory Xian
NHMRC Research Achievements - SUMMARY
Email/Phone no. of contact:
cory.xian@unisa.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 508047
CIA Name: Prof Cory Xian
Admin Inst: University of South Australia
Main RFCD: Orthopaedics
Total funding: $617,879
Start Year: 2008
End Year: 2012
Grant Type: NHMRC Research Fellowships
Title of research award:
Uncoupled Research FellowshipUncoupled Research Fellowship
Lay Description (from application):
“I am a biomedical scientist undertaking basic and clinical research on the pathophysiology of growth plate
injury and repair, which critically impacts on children’s bone growth and growth disorders. I aim to investigate
the underlying mechanisms and deve
Research achievements (from final report):
Musculoskeletal conditions including skeletal fractures are major burdens on individuals and health systems.
Childhood bone health is critical for ensuring healthy development, and the peak bone mass achieved in
adolescence and early adulthood also profoundly influences adult bone health. During 2008-2012 with
NHMRC SRF support, I have made following research achievements in three major areas. Injured growth plate
is often "faultily" repaired leading to bone growth defects. My laboratory has identified a sequential injury
repair response and potential targets which could lead to development of a biological treatment. Cancer
chemotherapy unfortunately causes significant bone defects (osteoporosis, marrow adiposity and fractures). My
laboratory has identified that these defects result from reduced bone formation, increased bone resorption, and
increased marrow fat formation, as well as involvement of major signalling pathways (Wnt/b-catenin and NF¿B). Our work also showed that supplementation with folinic acid (a folate analogue) or genistein (a soy
isoflavone) preserved bone mass in MTX-treated rats, and that anti-inflammatory fish oil and emu oil inhibited
bone loss during chemotherapy. Apart from genetics, bone growth is also influenced by nutrition and physical
activity, which are major influences that can be modified to optimise bone mass in childhood. We observed
that maternal fish oil supplementation during pregnancy and lactation improved offspring bone growth. We
demonstrated that soy isoflavone genistein promotes formation of bone forming cells (osteoblasts) and inhibits
formation of bone degrading cells (osteoclasts), and that icariin (a flavonol glycoside from the herb
Epimedium) is more potent than genistein in promoting osteoblast formation.
Expected future outcomes:
oPotential development of the first in situ biological regenerative therapy for children's growth plate trauma
injury-induced bone growth defects;oPotential identification of novel preventative strategies for bone and bone
marrow damage caused by chemotherapy;oPotential identification of dietary interventions for optimising bone
growth and bone mass accrual in early life.
Name of contact:
Prof Cory Xian
Email/Phone no. of contact:
cory.xian@unisa.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 571090
CIA Name: Prof G. Lorimer Moseley
Admin Inst: University of South Australia
Main RFCD: Central Nervous System
Total funding: $600,559
Start Year: 2009
End Year: 2013
Grant Type: NHMRC Research Fellowships
Title of research award:
Uncoupled Research FellowshipUncoupled Research Fellowship
Lay Description (from application):
I am a clinical scientist translating basic science findings into clinical science questions and answers that impart
better understanding and management of pain and painful disease.
Research achievements (from final report):
In the 5 years of this fellowship, I have built an interdisciplinary research team of 28+ members, been
appointed Professor of Clinical Neurosciences and Inaugural Chair in Physiotherapy at UniSA, the youngest
Chair in Medical or Allied Health at an Australian University; was made Fellow of the Australian College of
Physiotherapy; was runner-up for the 2012 Science Minister's Prize for Life Sciences; won the 2012 NHMRC
Marshall & Warren Award for the best innovative and potentially transformative project grant; have been
awarded 3 out of 4 NHMRC project grant submissions as CIA, two scoring '6- top quartile' scores; have given
the most prestigious plenary lecture in world physiotherapy and the keynote address at the American Pain
Congress; have conceived and established the PainAdelaide Stakeholders' Consortium, with a scientific
meeting, public lectures and the annual Ride for Pain (>550 community participants); have been the only nonEuropean invited to the European Union's Societal Impact of Pain Government/Industry forum; and established
the world's most influential pain-related web and social media presence - bodyinmind.org.
Expected future outcomes:
I commenced a PRF this year and my research group is testing three broad hypotheses, each with clear and
important implications for the management or treatment of people in pain. We are funded by NHMRC project
grants and fellowship support.
Name of contact:
Professor Lorimer Moseley
Email/Phone no. of contact:
Lorimer.moseley@unisa.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 595937
Start Year: 2010
CIA Name: Prof Xin-Fu Zhou
End Year: 2012
Admin Inst: University of South Australia
Grant Type: NHMRC Project Grants
Main RFCD: Neurosciences not elsewhere classified
Total funding: $496,205
Title of research award:
Roles of proBDNF in nerve regenerationRoles of proBDNF in nerve regeneration
Lay Description (from application):
Nerve growth factors are essential to promote nerve regeneration and are potential drugs for the treatment of
nervous disorders such as spinal cord injury. Our recent result demonstrates that the precursor form of the
nerve growth factor brain derived neurotrophic factor (proBDNF) is detrimental to an injured nervous system
and can cause nerve degeneration. This project further investigates the phenomenon in order to promote
treatment of spinal cord injury.
Research achievements (from final report):
Neurite growth is essential for neuronal polarity, neuronal connectivities during development, and is critical for
functional recovery after nerve injury. BDNF plays an important role in the regulation of neurite growth and
nerve regeneration after injury. Our previous studies funded by NHMRC grant (375109) showed that
peripherally derived mature BDNF plays a critical role in the enhanced regeneration of ascending and
descending spinal neurons after spinal cord injury. These studies provided basis for the peripheral application
of mature BDNF in the treatment of CNS injury. Our finding that proBDNF suppresses neurite growth and
regeneration is important as we have elucidated a novel role of this BDNF gene product. This study shift the
conceptual paradigm and generate a high impact results both in the field and across fields. Furthermore, we
tried to develop several potential drug molecules (mature BDNF-Fc, monoclonal antibody to prodomain,
Sortilin-Fc) which can be further developed for the treatment of spinal cord injury.
Expected future outcomes:
We have strong evidence that endogenous proBDNF is an inhibitory factor, pharmaceutical tools (proBDNF
monoclonal antibody, Sortilin ecd-Fc and mature BDNF-Fc) may be further developed for a clinical trial. A
combination of BDNF-Fc with anti-proBDNF will shift the conceptual paradigm in the field of spinal cord
injury.
Name of contact:
Xin-Fu Zhou
Email/Phone no. of contact:
zhou0010@gmail.com
NHMRC Research Achievements - SUMMARY
Grant ID: 1003433
CIA Name: A/Pr Paul Anderson
Admin Inst: University of South Australia
Main RFCD: Receptors and Membrane Biology
Total funding: $497,001
Start Year: 2011
End Year: 2013
Grant Type: NHMRC Project Grants
Title of research award:
Vitamin D Activity to Regulate Bone Remodelling and Promote Bone StrengthVitamin D Activity to Regulate
Bone Remodelling and Promote Bone Strength
Lay Description (from application):
While vitamin D and calcium supplementation is well known to protect against osteoporosis and hip fracture,
the mechanisms by which this occur are not fully understood. Thus, this project aims to establish the cellular
basis for the importance of direct action of vitamin D and calcium within the bone. This information is
necessary to develop public health nutritional recommendations for improving skeletal health and reducing the
incidence of hip factures in the elderly.
Research achievements (from final report):
This project was set to determine the mechanisms by which vitamin D directly regulates processes of bone
remodelling.We have demonstarted that mature osteoblast-specific deletion of VDR abrogates the regulation of
bone resorption by reducing RANKL-mediated signalling from osteoblasts. In addtion there was a significant
downturn in osteoblast-mediated bone formation with the absence of VDR. The net result of this change in
bone turnover was a profound increased bone volume particularly during periods of rapid growth where bone
turnover is typically high. However, osteocyte-specific VDR deletion did not result in decreased RANKL
signalling or change to bone volume. Thus, these studies demonstarte that mature osteoblasts in the preosteocyte phase are responsible for the regulating bone turnover. , A second aim was to identify whether overexpression of VDR within osteoblasts in a transgenic model is capable of enhancing vitamin D activities to
regulate bone turnover. The original hypothesis, based on intial findings, was that enhanced VDR-mediated
siganlling leads to net imcrease in bone volume due to increased bone formation. However, we demonstrated
that while enhanced VDR-mediated siganlling in osteoblasts always leads in increased bone formation, in the
presence of high circulating active vitamin D (1,25D) levels, enhanced RANKL-mediated bone resoprtion
occurs due to incressed VDR levels and results in a overall loss in bone volume. Thus, only under
circumstances of low circulating 1,25D levels, does processes of bone formation lead to increased bone mineral
volume and stength. , The clinical benefits of this knowledge are that while most people would refer to serum
pre-cursor for vitamin D (25D) as a indicator of bone health, determining serum 1,25D levels and ensuring that
these levels are not raised, partucualrly during rapid growth, may benefit bone mieral accrual during
adolescence which is key to prevention of osteoporosis later in life.
Expected future outcomes:
We are now regulating the synthesis and/or catabolism of active vitamin D within osteoblasts themselves.
Current data suggest that enhancing local synthesis of 1,25D is pro-anabolic. Secondly, we are using analogues
to active vitamin D to determine whether we can illicit a bone formation response without activating bone
resoprtion. Both approches have clinical applications.
Name of contact:
A/Prof Paul Anderson
Email/Phone no. of contact:
paul.anderson@unisa.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 107203
Start Year: 2000
CIA Name: Prof Kathryn Refshauge
End Year: 2002
Admin Inst: University of Sydney
Grant Type: NHMRC Project Grants
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $234,602
Title of research award:
Exercise or advice for sub-acute low back pain?Exercise or advice for sub-acute low back pain?
Lay Description (from application):
Low back pain (LBP) is highly prevalent and enormously expensive to society: total payments made by
Workcover for injuries to the low back were in excess of $530 million in NSW in 1996. Chronic LBP (pain
lasting more than 3 months) accounts for up to 90% of these costs. Prevention of a large part of this costly
problem could be achieved by effective treatment at the earlier sub-acute phase of LBP (6 weeks to 3 months
duration). Exercise and advice are two widely-used treatments for sub-acute LBP, yet remarkably, their
efficacy is unknown. For the first time, this study will rigorously evaluate the effectiveness of both a
supervised exercise program and advice to return to normal activity for sub-acute LBP. When this study is
completed, Australian practitioners will be able to adopt evidence based practice when managing sub-acute
LBP. In addition, the study's results will enable practitioners to select the most effective treatment for each
individual patient. The results of this study should lead to a large reduction in the incidence of chronic LBP,
therefore the results should lead to significant savings in terms of social and economic costs.
Research achievements (from final report):
N/A
Expected future outcomes:
We will complete analysis of three month and 12 month outcome data within the next three months. We will
also analyse the data about predictors of prognosis for subacute low back pain, determining who responds best
to exercise or advice. Our findings to date provide evidence that exercise and advice are effective treatments to
decrease pain and disability for subacute low back pain. However, there are many different types of exercise
programs, and we investigated only one form of exercise. We will continue this research program by
investigating the most effective types of exercise and the most successful methods of implementation. In
addition, we are currently extending the findings of the systematic review by conducting a rigorous study to
determine accurately the prognosis of acute low back pain. We will also determine the accuracy of diagnosis of
spinal pathology from questions asked in the history. The ultimate benefits of our research progam are that
patients with low back pain will be treated more effectively, and more accurate predictions of prognosis can be
made.
Name of contact:
N/A
Email/Phone no. of contact:
N/A
NHMRC Research Achievements - SUMMARY
Grant ID: 153712
CIA Name: Prof Stephen MacMahon
Admin Inst: University of Sydney
Main RFCD: Orthopaedics
Total funding: $364,218
Start Year: 2001
End Year: 2003
Grant Type: NHMRC Project Grants
Title of research award:
Randomised trial of ibuprofen for the prevention of ectopic bone-related pain and disability after hip
replacementRandomised trial of ibuprofen for the prevention of ectopic bone-related pain and disability after
hip replacement
Lay Description (from application):
Joint replacement is a well-established treatment for severe osteoarthritis of the hip. While most patients
benefit substantially from the procedure, many still experience some pain and disability after surgery. New
evidence suggests that one important cause of this pain and disability may be abnormal bone deposits that form
in the muscles around the hip (ectopic bone formation) during the first few months after surgery. Ectopic bone
formation is seen in about 40% of all patients with hip replacements. If the formation is extensive, all
movement of the hip is lost and revision surgery is necessary. However, even when the formation is less
severe, movement at the hip can be restricted resulting in pain and disability. There is growing evidence that
treatment with a non-steroidal anti-inflammatory drug at the time of surgery may halve the risk of ectopic bone
formation. While this would be expected to decrease the risk and severity of post-operative pain and disability,
there is little evidence available about the long-term effects of these drugs after hip replacement. For this
reason, together with concerns about possible side-effect of these drugs, orthopaedic surgeons have generally
been reluctant to prescribe these drugs routinely for the prevention of ectopic bone formation. Ibuprofen
appears to be the non-steroidal anti-inflammatory drug with the lowest risk of side effects. If it was shown to
be effective in reducing the incidence of pain and disability associated with ectopic bone formation after hip
replacement, it may well be considered worthwhile by doctors and patients alike. If such benefits were
realised, this preventive strategy is likely to be a highly cost-effective way to improve long-term outcome
among the rapidly growing numbers of patients that receive hip replacements. This study will provide reliable
evidence about the short and long-term effects of ibuprofen among 1,000 patients receiving hip replacements in
Australia.
Research achievements (from final report):
Worldwide, HIPAID is the largest randomised clinical trial conducted to date investigating the risks and overall
benefits of a perioperative course of a non-steroidal anti-inflammatory drug (ibuprofen) amongst people
undergoing elective hip replacement surgery. 902 patients were randomised from more than 20 orthopaedic
surgery centres throughout Australia and New Zealand. Bleeding and adverse events were closely monitored
during the study treatment period. Benefits were assessed 6 to 12 months after surgery and included a wide
range of both well-validated patient self-reported outcomes (pain, physical function, general health status and
global assessments of treatment effectiveness) as well as objective measures of physical performance (range of
hip flexion, walking speed). Loss to followup was minimal: less than 6% for the main outcome: self-reported
physical function. HIPAID confirmed that hip replacement surgery is extremely beneficial for most patients
with osteoarthritis, resulting in greatly reduced pain and improved physical function and mobility. HIPAID also
confirmed that more than 40% of patients will develop ectopic bone after elective hip replacement surgery and
that a short perioperative course of ibuprofen (1200mg for 14 days) will significantly reduce the risk of
developing ectopic bone without significantly increasing bleeding or the rate of adverse events. However, the
periooperative anti-inflammatory treatment did not appear to markedly improve the considerable long-term
benefits already achieved by the hip replacement surgery.
Expected future outcomes:
This unique data set will be further explored to analyse how closely ectopic bone is associated to poor outcome
and if any patient characteristics or peri-operative events increase the risk of developing ectopic bone or poor
outcomes to surgery (approximately 15% of this sample did not report that their hip was 'much better' after
surgery.
NHMRC Research Achievements - SUMMARY
Name of contact:
Dr Marlene Fransen
Email/Phone no. of contact:
mfransen@thegeorgeinstitute.org
NHMRC Research Achievements - SUMMARY
Grant ID: 211023
Start Year: 2002
CIA Name: Prof Paul Pilowsky
End Year: 2006
Admin Inst: University of Sydney
Grant Type: NHMRC Project Grants
Main RFCD: Cardiology (incl. Cardiovascular Diseases)
Total funding: $941,350
Title of research award:
Central control of blood pressure: neurotransmitters, receptors, signal transduction and gene expressionCentral
control of blood pressure: neurotransmitters, receptors, signal transduction and gene expression
Lay Description (from application):
The way that the brain controls blood pressure is of crucial significance to our day-to-day survival. Nerves in
the lower brain and spinal cord cause blood pressure to be maintained at appropriate levels for all types of daily
activities ranging from sleep, when blood pressure is very low, to exercise when blood pressure can be very
high. In hypertension, a disorder that afflicts around 10% of the community, blood pressure is elevated to an
extent that damages organs such as the brain, heart, kidney and eye. It now appears that most cases of
hypertension have as their basis a disorder of the way that the brain, through the sympathetic nervous system,
controls the heart and blood vessels. Many different brain systems need to change the way that blood is
distributed in the body at different times. For example, when we eat, blood goes preferentially to our gut; if we
exercise, to our heart and muscles; if we are cold, to our skin and when we think, to our brain. This
specialised regulation of blood flow is accomplished by the interaction of nerves in the lower brain and spinal
cord. It involves a vast array of special chemical messengers acting on specific receptors through different
intracellular mechanisms and involving the turning on or off of genes. Only a few of these neurotransmitter
systems are well understood. At the core of our proposal, we aim to determine which neurotransmitters
systems are important for which cardiovascular functions. We anticipate that this new information will permit
the development of new approaches to the management of hypertension. The reason for this is that since
different pathways use different messenger systems, it should become possible to tailor therapy to suit
hypertension without causing undesirable side-effects.
Research achievements (from final report):
The major scientific achievements of our research program have been to increase understanding about the way
that the brain controls blood pressure and which chemicals are important in this regulation. Our work has a
special focus on a part of the brainstem called the rostral ventrolateral medulla since this area is known to be
crucial for maintaining normal blood pressure and in responding to reflexes such as low oxygen reflexes and
high pressure. The Funds awarded resulted in the publication of 30 peer-reviewed scholarly articles in major
international journals. Twelve PhD students received training during this period and worked on activities
related to this grant, and five of these candidates have completed their degrees. Thirteen students worked on
Honours degrees successfully during this period with twelve achieving a first class result. The potential benefit
of our work can be understood in terms of the acquisition of new knowledge about the central control of the
cardiorespiratory system which will likely lead to the development of novel forms of therapy for cardiovascular
and respiratory diseases which together are major causes of sickness and death in our society. Training is not to
be underestimated. Our successful students continue as medical doctors, dentists and specialists or combine
these activities; others work in high-technology industry, directly benefiting our economy.
Expected future outcomes:
We anticipate that the work conducted with funds from this grant will result in direct benefits in understanding
how the brain and heart work thereby leading to new treatment for disease. The importance of training young
graduates cannot be underestimated.
Name of contact:
Professor P M Pilowsky
Email/Phone no. of contact:
paul.pilowsky@mq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 211031
CIA Name: Prof Robert Cumming
Admin Inst: University of Sydney
Main RFCD: Preventive Medicine
Total funding: $403,892
Start Year: 2002
End Year: 2004
Grant Type: NHMRC Project Grants
Title of research award:
Improving vision to prevent falls: a randomized trialImproving vision to prevent falls: a randomized trial
Lay Description (from application):
More than 30% of older Australians fall over at least once a year. Poor eyesight, another very common problem
among older Australians, increases the risk of falling. In fact, recent evidence from the Blue Mountains Eye
Study suggests that poor vision is one of the strongest risk factors for falls and fractures yet identied. Our
project is designed to assess whether improving vision will decrease the chance of falls and fractures. We will
recruit 1200 people aged 75 years and over from among those attending community-based aged care services in
the inner western suburbs of Sydney. If they consent to participate, people will be randomly allocated to either
an intervention or control group. Those in the intervention group will receive a simple, yet comprehensive,
series of vision and eye tests. These tests will be done by an optometrist, either in subjects' homes or at the
study centre. Our previous research suggests that nearly 50% of subjects will benefit from having new glasses
and 10% might require cataract surgery. If necessary, treatment will be paid for from study funds. Some vision
problems cannot be fixed. In these cases, an occupational therapist will arrange appropriate home modifications
to improve vision-related function. Subjects will be followed-up for 12 months to assess the frequency of falls
in the intervention and control groups. We hope to find a 33% reduction in falls in the intervention group. We
will follow subjects for a further year to identify fractures.
Research achievements (from final report):
This is a 3-year randomized trial evaluating vision testing and treatment for prevention of falls in older people.
Final follow-up of subjects is only just complete and data analysis is underway. No results are yet available.
Expected future outcomes:
This project will provide important information about the need for additional eye services to prevent falls in
older people
Name of contact:
Robert G Cumming
Email/Phone no. of contact:
bobc@health.usyd.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 211046
CIA Name: Prof Robyn Norton
Admin Inst: University of Sydney
Main RFCD: Epidemiology
Total funding: $689,830
Start Year: 2002
End Year: 2004
Grant Type: NHMRC Project Grants
Title of research award:
Cohort study of risk factors for young driver injuriesCohort study of risk factors for young driver injuries
Lay Description (from application):
Injuries impose a substantial burden on young people, both in Australia and internationally. In 1998, 70% of
all deaths among young men, and 57% of deaths among young women, aged 15-24 years in Australia were due
to injuries. The single largest cause of injury-related fatalities, hospital admissions and emergency department
presentations among this age group is transport-related incidents. Technological advances in motor vehicle
engineering and road design, and the implementation of various road safety measures, such as random breath
testing, have led to an overall decline in the incidence of motor vehicle-related injuries in Australia in the past
three decades. However, young people still have substantially higher rates of motor vehicle-related mortality
than older people. This suggests that if the burden of injuries among young drivers is to be reduced to levels
that are at least as comparable with those in other age-groups, then the identification of factors that are
specifically associated with an increased risk of motor vehicle injury among young people, must be a priority.
The current study aims to determine the role of several postulated risk factors in the incidence of young driver
injuries. The specific risk factors to be examined include pre-licence road and driving exposure/experience;
type, quality and quantity of driver training; and road risk perceptions and engagement in sensation seeking
behaviours. The study also seeks to determine whether factors associated with increased risk of driver injury
are the same for different socio-economic groups and for different ethnic and cultural groups. Information
obtained in this study should provide reliable evidence about causal factors for motor vehicle crash injury
among young drivers. Such information should be useful to licensing and road safety professionals, in the
design of practical road safety strategies aimed at reducing the burden of young driver injuries.
Research achievements (from final report):
With the successful recruitment of over 20,000 drivers aged 17-24 years, the DRIVE Study is one of the largest
cohort studies examining risk factors for young driver injury in Australia and internationally. The use of a
robust cohort methodology and linkage to routinely collected data sources for outcome measures, allows
minimal opportunity for bias. As a result, the DRIVE Study will provide results that will have significant road
safety policy implications for Australian and other jurisdictions. The success of baseline data collection aided
by use of web-based data collection techniques has provided investigators with a valuable set of indicators for
road traffic injury in young people. Future use of the data by policy makers and road safety jurisdictional
authorities is expected to be significant. Planned linkages to resurvey data and outcome data, expected to occur
in mid 2006, will allow the provision of valuable data in the field of young driver injury in years to come.
Expected future outcomes:
The DRIVE Study will provide high quality evidence about the strength and direction of risk factors for young
driver serious injury and death, including driver training, risk perception, driver behaviour and mental health.
This information will contribute significantly to the improved management of young driver safety in Australia,
and internationally.
Name of contact:
Dr Rebecca Ivers
Email/Phone no. of contact:
rivers@thegeorgeinstitute.org
NHMRC Research Achievements - SUMMARY
Grant ID: 211168
CIA Name: Prof MacDonald Christie
Admin Inst: University of Sydney
Main RFCD: Cellular Nervous System
Total funding: $285,990
Start Year: 2002
End Year: 2004
Grant Type: NHMRC Project Grants
Title of research award:
Differentiation of multiple phenotypes of rostral ventromedial medulla neurons and their role in
painDifferentiation of multiple phenotypes of rostral ventromedial medulla neurons and their role in pain
Lay Description (from application):
Chronic pain, defined as pain experienced in three out of a six month pre-interview period affects 17% of
males and 20% of females in the Australian population. Opioid drugs such as morphine and codeine are the
most effective drugs used to treat moderate to severe pain. However, the utility of these drugs is hampered by
the development of a blunted response with repeated use. Furthermore, some clinically important pain states,
particularly those caused by nerve injury, do not respond well to opioid drugs. Recent basic neurosceince
research has identified groups of nerve cells deep within the brain that control sensitivity to pain as pain signals
enter the spinal cord. Unfortunately in the presence of some chronic pain conditions, or chronic use of high
doses of opioid drugs, these neurons undergo functional changes or adaptations that distort and increase the
severity of pain sensation in a more or less permanent manner. This project uses electrical and chemical
techniques to identify the basic physiology and pharmacology of single nerve cells in this brain region, so that
their normal functions can be properly understood. We will then identify the cellular and molecular adaptations
that occur in the nerve cells in animal models of chronic nerve injury and chronic morphine treatment to
identify the nature of adaptations responsible for their aberrant function. We will then be in a position to
rationally identify novel drug targets that can normalise the function of these nerve cells. This knowledge will
provide potential targets for development of novel therapeutics to manage chronic pain.
Research achievements (from final report):
The brain has evolved mechanisms to control pain. The major anatomical system, the descending pain
modulatory network, uses endogenous opioids and is a major target of pain relieving drugs such as morphine.
We determined the organization of neurons in a pivotal component of the system deep in the brain stem and
delineated physiology, and neurochemistry of opioid-sensitivecells that send modulatory information to the
main pain sensing region of the spinal cord. We have discovered for the first that a major component of this
opioid-sensitive network is composed of GABAergic neurons that project to the spinal cord. Most projecting
GABAergic cells respond to the main opioid analgesics, the mu-receptor opioids. This has strong implications
for development of GABAergic therapeutics that act in the spinal cord. We discovered that other opioid
receptors are present on sub-populations of these nerves as well, particularly kappa-opioids and for the first
time delta opioids. This has led to revision of previously oversimplistic models of this descending network that
proposed that the major types of neurons controlling pain from the brain to the spinal cord were serotonergic
and glutamatergic. We are now beginning to understand how this descending pain modulating system
modulates spinal cord pain responsiveness, as well as how the system fails in chronic pain states and after
chronic morphine treatment.
Expected future outcomes:
Understanding adaptations of inputs to GABAergic neurons that project to the spinal cord form lower brain
sites will lead to a proper description of adaptations of these pathways that are widely thought to underlie some
aspects of chronic pain and why opioids fail to work after continued use.
Name of contact:
Macdonald Christie
Email/Phone no. of contact:
macc@med.usyd.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 211226
Start Year: 2002
CIA Name: Prof Maria Fiatarone Singh
End Year: 2006
Admin Inst: University of Sydney
Grant Type: NHMRC Project Grants
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $819,180
Title of research award:
Hip Fracture Intervention Trial (HIPFIT)Hip Fracture Intervention Trial (HIPFIT)
Lay Description (from application):
Hip fracture secondary to falling in the elderly represents a large and rising health care problem in Australia. At
least 12,000 such hip fractures occur in the elderly in Australia each year and this number is expected to
increase substantially over the next several decades. Long term disability, nursing home placement, reduced
quality of life, and excess mortality are known sequelae of hip fracture despite successful surgical repair.
Factors have been previous identified in epidemiological research which predict poor recovery of function and
the most prominent of these are advanced age, pre-exiting mental or functional impairment, malnutrition,
depression, poor social support networks, and poor gait, balance and muscle function. Current treatment
paradigms for hip fracture do not uniformly screen for or appropriately address potentially reversible factors
such as poor nutrition, neuromuscular dysfunction, depression, strength of social supports, or risk factors for
recurrent injurious falls. It is unlikely that a unidimensional treatment will ever optimize long term functional
independence in such a multifactorial syndrome. Therefore, we propose to apply a multifaceted targeted
experimental treatment package (HIPFIT) to elderly patients admitted to hospital for repair of a fractured hip
secondary to a fall. HIPFIT would begin in hospital and continue throughout the 12 months of follow up, using
individualized treatment strategies based on periodic reassessments in these vital domains over time. The goal
of the study is to reduce the number of patients requiring nursing home care at the end of 12 months, as well as
to improve independence in a range of activities of daily living among experimental subjects. This would have
significance not only in terms of large economic savings for the health care system but reduced personal
suffering and dependency on the part of the affected individuals.
Research achievements (from final report):
Between February 2003 & April 2007 we identified 1748 individuals (60% women) admitted to RPA Hospital
with potential hip fractures (median age 80 y). A total of 262 patients were found eligible for the study and
approached for their consent which was obtained from 124 patients (47% of eligible). Three assessments were
completed per participant: a total of 111 post hip fracture, 98 after 4 months & 87 after 12 months. The 12
months intervention was implemented for 85% of the participants randomised to intervention. Drop-out rate
was 10%, lower than we conservatively anticipated, and death rate was also 10%. , This is the first study to
target all major remediable contributions to recovery of function after hip fracture, including a multicomponent intervention directed at fall risk in the home, bone health, sarcopenia, muscle weakness, gait and
balance impairment, depression, cognitive impairment, nutritional deficiencies, low self-efficacy, low social
support, polypharmacy, and visual impairment. The robust RCT design, supervised 12 month intervention, and
long-term followup of functional status and place of residence/death over 5 years make this study completely
unique internationally, and a critical addition to clinical practice in this area. If the intervention proves
successful as we complete our analyses of primary and secondary outcomes, we will have demonstrated an
approach that can be implemented directly into existing health care infrastructure in Australia, as this study was
carried out in the outpatient clinic of a hospital using a variety of health care professionals who typically work
in such a setting. However, the approach we took to proactively identifying and aggressively treating
etiological factors in hip fracture-related incidence and recovery is not currently the standard of care in
Australia or elsewhere, and translation of this approach to the community will require substantive and vitallyneeded educational and implementation strategies.
Expected future outcomes:
Training of health care professionals to implement this intervention in health care settings throughout Australia
and internationally., Development of multi-medial training materials to allow translational research and
dissemination into community settings.
NHMRC Research Achievements - SUMMARY
Name of contact:
Maria A. Fiatarone Singh
Email/Phone no. of contact:
m.singh@usyd.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 211254
Start Year: 2002
CIA Name: Dr Anne Moseley
End Year: 2003
Admin Inst: University of Sydney
Grant Type: NHMRC Project Grants
Main RFCD: Rehabilitation and Therapy: Occupational and Physical
Total funding: $55,220
Title of research award:
Randomised controlled trial of stretching for contracture after ankle fractureRandomised controlled trial of
stretching for contracture after ankle fracture
Lay Description (from application):
Restricted ankle motion (contracture) commonly occurs after cast immobilisation following ankle fracture. The
prevalence of contracture could be as high as 77% immediately following cast removal. This interferes with
tasks such as walking and stair climbing, and can result in significant disability. While physiotherapists
regularly treat contracture after ankle fracture, the efficacy of specific treatment programs has not been
established. This project aims to determine the effectiveness of two commonly used stretching programs for
contracture after ankle fracture initially treated with cast immobilisation. Stretches of short and long duration
will be compared to a no stretch condition. The study will determine the effects of these interventions on ankle
flexibility, ability to perform everyday tasks (eg, walking), self-ratings of disability and pain.
Research achievements (from final report):
A common sequel of cast immobilisation for ankle fracture is loss of ankle joint range of motion. This is often
treated by a program of stretching, but it is not known how much stretch is required or if, for that matter,
stretch is effective. The aim of this study was to compare the effects of short (6 minutes) and long (30 minutes)
duration stretches with a control condition for the treatment of contracture after ankle fracture. Our multicentre, assessor blinded randomised controlled trial revealed that the addition of a program of passive stretches
confers no benefit over exercise alone for the treatment of plantarflexion contracture after cast immobilisation
for ankle fracture.
Expected future outcomes:
Now that it has been shown that a clinical stretching protocol does not increase joint range of motion or reduce
disability in people with contracture following cast immobilisation for ankle fracture, physiotherapists can
discontinue prescription of stretching programs as part of the routine management of ankle fractures.
Name of contact:
Dr Anne Moseley
Email/Phone no. of contact:
amoseley@mail.usyd.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 211256
Start Year: 2002
CIA Name: Prof Ian Cameron
End Year: 2004
Admin Inst: University of Sydney
Grant Type: NHMRC Project Grants
Main RFCD: Public Health and Health Services not elsewhere classified
Total funding: $209,865
Title of research award:
Enhancing mobility after hip fractureEnhancing mobility after hip fracture
Lay Description (from application):
Many older people who fracture their hip do not recover to their previous level of function. This study will test
whether it is possible to help recovery of function, particularly walking, after hip fracture by using different
and more intensive physiotherapy treatment. The treatment will concentrate on exercise when standing, will be
provided twice daily and will continue after the person with hip fracture has returned home. Four months after
the hip fracture it is expected that walking ability, strength and balance will be improved by the new treatment
methods.
Research achievements (from final report):
The project has investigated what constitutes effective retraining of mobility after hip fracture in older people.
A randomised trial has been conducted with masked outcome assessment. The novel treatment is an intensive
weight-bearing exercise program, while the control group has had a conventional exercise program. The
treatments have been well tolerated and the full study sample of 160 people have been recruited. It has been
shown that frail older people can participate in an intensive exercise program after hip fracture.
Expected future outcomes:
Details of the effective mobility retraining program will be published
Name of contact:
Ian Cameron
Email/Phone no. of contact:
ianc@mail.usyd.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 211266
CIA Name: Dr James Melrose
Admin Inst: University of Sydney
Main RFCD: Orthopaedics
Total funding: $331,320
Start Year: 2002
End Year: 2004
Grant Type: NHMRC Project Grants
Title of research award:
INVESTIGATIONS ON THE REGULATION OF INTERVERTEBRAL DISC CELL MATRIX
METALLOPROTEINASESINVESTIGATIONS ON THE REGULATION OF INTERVERTEBRAL DISC
CELL MATRIX METALLOPROTEINASES
Lay Description (from application):
Degeneration of the intervertebral disc is a painful disabling condition with major socioeconomic
consequences. Medical problems associated with disc degeneration and back-pain, of sufficient severity to
warrant consultation with a physician, are experienced by 90% of the population some time during their lives.
In man, back pain increases in incidence in the third and fourth decades of life, peaks in the fifties and declines
thereafter. Changes in population demographics indicate this problem will increase in severity over the next
few decades. American Bureau of Census data indicate that between 1990 to 2010 the number of people >45
years will increase from 82 to 124 million, the number of elderly in emerging countries will also increase
between 200 to 400% in the next 30 years. In the United States, back-pain is the second most common reason
that people visit a physician and medical conditions related to back-pain account for more hospitalisations than
any other musculoskeletal disorder. Despite its high incidence, associated problems of incapacity and economic
implications, costed at $100 million per annum in Australia in 1992, and US$100 billion globally in 1999-2000
(Dorland Data Networks, PA, USA) the causes of low back-pain are still poorly understood. Disc disease is
responsible for 23-40% of all cases of low back-pain. The management of discogenic low back-pain is
currently empirical, directed either toward life-style changes to minimise symptomatology or to surgical
resection or spinal arthrodesis to restrict articulation. Based on our recent findings and those of colleagues over
the last 16 years, it is our strong conviction that it should be possible with a better understanding of disease
mechanisms and with the use of modern technologies to inhibit, reverse or ideally prevent disc degeneration.
Without such basic research there will be no scientific foundation upon which prospective therapies may be
based.
Research achievements (from final report):
Defects in the intervertebral disc are difficult to treat clinically and may be a source of intense low back pain,
furthermore overloading of a biomechanically compromised disc may exacerbate this condition and lead to
propogation of the defect to other neurological structures which may also be a source of intense pain. In dense
avascular connective tissues such as the intervertebral disc the normal healing response to a traumatic insult
leading to formation of a defect in this important weight bearing structure is to lay down a stabilising
collagenous scar tissue in the defect site. Unfortunately, such scar tissue is generally less compliant and less
capable of acting as a weight bearing structure than the native connective tissue of the disc. Replacement of
scar tissue with new functional weight bearing connective tissue is only possible if the endogenous connective
tissue cells remodel the scar tissue and replace it with new functional tissue. Intervertebral disc cells are not a
particularly active metabolic cell type thus agents have been sought which can increase their cellular
metabolism to encourage them to remodel connective tissue and reconstruct mechanically damaged regions of
the disc. Such an approach has provided encouraging results in-vitro with regard to the remodelling of major
structural components of scar tissue, namely collagen and its proteoglycans. On-going studies in animal models
in which intervertebral disc defects are reproduced surgically may provide significant insights as to how dense
avascular connective tissues may be remobilised to provide new functional weight bearing connective tissues.
Expected future outcomes:
Improvement in the recovery of trauma defects in dense avascular connective tissues such as intervertebral disc
and tendon would be expected to improve their functional status and aid in the rehabilitation of affected
individuals and the mobility of the general population.,
NHMRC Research Achievements - SUMMARY
Name of contact:
James
Email/Phone no. of contact:
jmelrose@med.usyd.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 211278
CIA Name: Prof Philip Sambrook
Admin Inst: University of Sydney
Main RFCD: Geriatrics and Gerontology
Total funding: $340,550
Start Year: 2002
End Year: 2004
Grant Type: NHMRC Project Grants
Title of research award:
Epidemiology of Osteoporotic Fractures in the Very Frail Elderly: Risk factors, Quality of Life and
MortalityEpidemiology of Osteoporotic Fractures in the Very Frail Elderly: Risk factors, Quality of Life and
Mortality
Lay Description (from application):
Osteoporosis, a disease characterised by skeletal fragility, is a major public health problem. The direct costs
alone of treating osteoporotic fractures have been estimated at more than $800 million in Australia. Hip
fractures are the most costly to treat and are due to a fall or injury in over 90% of cases. The frail elderly are at
particular risk of osteoporotic fractures but little is known about risk fractures in this 'at risk' group or the effect
of fracture on quality of life. This study is examining risk factors for fractures in the frail and institutionalised
older person by asessment of quantitative bone ultrasound, falls risk, vitamin D status and other biochemical
markers of bone in an attempt to identify predictors that can be modified to reduce fractures, improve quality of
life and reduce mortality due to osteoporotic fractures.
Research achievements (from final report):
In 1999, the NHMRC funded a 3 year Project Grant to assess the role of calcaneal ultrasound combined with
falls risk factors as a screening tool in a high risk population (the frail older person) for identifying those at risk
of osteoporotic fractures. This funding was extended between 2002 and 2004. Nursing homes and hostels in
northern Sydney were randomly selected from all such institutions within the Northern Sydney Area Health
Service and all residents over the age of 65 were asked to participate. The study, which recruited 2005 subjects.
, Findings from the FREE Study include a very high prevalence of vitamin D deficiency as noted above, a very
high falls rate and a high fracture incidence. We observed 181 hip fractures with a rate of 367 per 10,000
person years or 8.6 % over median 2.4 years followup. For total fractures, we observed 402 fractures during
3240 years of follow-up with an overall rate of 1241 per 10,000 (compared with 295 per 10,000 for community
dwelling women in the Dubbo Osteoporosis Epidemiology Study) or 16.8% after 19.4 months of follow-up.
Our study identfied tools that can be used to predict future falls and fractures.
Expected future outcomes:
Further publications will refine these tools to allow prediction of those at high risk of fracture and falls and
allow preventive measures.
Name of contact:
Philip Sambrook
Email/Phone no. of contact:
sambrook@med..usyd.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 211279
CIA Name: A/Pr Lyn March
Admin Inst: University of Sydney
Main RFCD: Orthopaedics
Total funding: $360,660
Start Year: 2002
End Year: 2006
Grant Type: NHMRC Project Grants
Title of research award:
Economic Evaluation and Health Outcomes of Arthritis and its TreatmentsEconomic Evaluation and Health
Outcomes of Arthritis and its Treatments
Lay Description (from application):
Musculoskeletal diseases are the most common single cause of chronic disability in Australia and total joint
replacement is rapidly becoming one of the most commonly performed operations. This burden of illness is
likely to increase with our ageing population and there is an urgent need to obtain data relating to the costs and
outcomes in the Australian context so that appropriate planning of health services and resources can be carried
out. The WHO (World Health Organisation) has declared 2000 to 2010 the Bone and Joint Decade,
recommending that research into musculoskeletal disorders be a priority. We have been recruiting and
following a unique cohort of osteoarthritis and rheumatoid arthritis patients, from both the public and private
health sectors, who have been carefully documenting their health outcomes, health care costs (including
primary, revision and bilateral hip and knee joint replacement surgery), out-of-pocket and indirect costs related
to their arthritis. Long-term follow-up is now essential to obtain a clear picture of the impact of living with
arthritis over time and the cost-effectiveness and predictors of good and bad outcomes of joint replacement
surgery. The information derived from this study will be useful for patients and doctors in making their
decisions about treatments, as well as for health care providers in planning of health services for arthritis
sufferers. Given that the cohorts are already established, the study is in a unique position to provide ongoing
important longer-term data for relatively low cost.
Research achievements (from final report):
We have established a unique cohort of over 900 arthritis subjects (244 non-surgical and 687 surgical including revision and bilateral arthroplasty). A relatively high proportion of the cohort has been maintained
considering the age of the participants and the amount of commitment required from participants. This was
done using regular telephone contact, quarterly newsletters, birthday cards, certificates of appreciation and
decorative magnets., Analysis of costs and health outcomes over 9 years for the non-surgical cohort showed
that disease progression in the OA group was slow, with slight non-significant deterioration in health status
measures. The health status of the RA group deteriorated significantly over the 9 years. Out-of-pocket
expenditure increased significantly for OA subjects from $247 to $548 per 3 months, but remained relatively
stable for the RA subjects, increasing from $367 to $397 for each 3 month period., Significant improvement
from pre-surgery to 12 months post-surgery was shown. The OA group then showed no deterioration in
function or increase in pain over the following eight years, despite a worsening in general health status which
may be attributed to aging of the cohort. No increase was seen in out-of-pocket expenditure over the eight year
period. It appears that joint replacement sugery amongst this cohort is showing a sustained beneficial impact in
terms of costs and outcomes at 8 years post-surgery.
Expected future outcomes:
An assessment of pre-operative self-efficacy amongst the recently recruited patients has shown that higher selfefficacy was associated with better health status & lower costs to both the respondent & health system. Selfefficacy is amenable to change, so these preliminary cross-sectional results suggest that increasing patients'
self-efficacy may improve post-operative outcome and reduce costs.
Name of contact:
A/Prof Lyn March
Email/Phone no. of contact:
lynmar@med.usyd.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID: 219307
CIA Name: Prof David Le Couteur
Admin Inst: University of Sydney
Main RFCD: Geriatrics and Gerontology
Total funding: $162,750
Start Year: 2003
End Year: 2006
Grant Type: SRDC - Research
Title of research award:
Australian Ageing Alliance: Geriatric Pharmacolog