Potential MBBS Research Projects: Honours, MPhil, PhD Students with a ‘genuine interest’ in any of the following projects or areas of research are encouraged to enquire by email to the contact person listed and discuss possible project opportunities NEW Projects Update #34: September 2014 Please also see individual websites: Queensland Institute For Medical Research (QIMR) Projects here Diamantina Institute List of Student Projects below and HERE Burns, Trauma and Critical Care Research Centre Research projects & opportunities Centre for Advanced Imaging (CAI) List of projects and research areas HERE Discipline Of General Practice QCPRRC: Cerebral Palsy & Rehabilitation Research Centre o List of projects for Honours, MPhil or PhD Faculty Of Health Sciences Research Queensland Brain Institute (QBI) UQ Centre for Clinical Research (CCR) Paediatrics & Child Health Research Opportunities Centre For Longitudinal and Life-course Research SPH Student Projects Sunshine Coast Clinical School (SCCS) Projects here Queensland Children's Medical Research Institute o Projects: Children's Burns & Trauma Research Queensland Centre for Intellectual and Developmental Disability Environment and Population Health Projects HERE Rural Clinical School Research Centre RCSRC Projects Centre for Youth Substance Abuse: Centre for Youth Substance Abuse 1 RESEARCH AREA or TOPIC CONTACT PERSON - Oral peptide drug delivery in inflammatory bowel disease Jakob Begun NAME CONTACT jakob.begun@mater.uq.edu.au EMAIL / PHONE Background: Inflammatory bowel disease(IBD) is a chronic inflammatory condition affecting the gastrointestinal tract of children and adults due to an inappropriate immune response to resident gut bacteria. Medical treatment has progressed significantly through a better understanding of the mechanism of disease, resulting in a better quality of life for many patients, but there remains a need for more effective and targeted therapy. IL-22 has emerged as an important cytokine produced by macrophages and type-3 innate lymphoid cells during colonic inflammation. In mice, overexpression of IL-22 in the colon reduces the level of inflammation. Oral delivery of peptides is challenging due to the numerous proteases and harsh environment of the gut but nanoparticles have emerged as a novel mode of delivery that may allow delivery of anti-inflammatory cytokines to sites of gut inflammation. This project focuses on developing orally available IL-22 and testing its efficacy in a murine model of colitis. Project description: Using a stable cell line expressing an IL-22 reporter recombinant IL-22 bound to a variety of nanoparticles provided by collaborators will be tested for receptor activity. Particles with optimal stimulation properties will be further tested in epithelial cell lines and activation of endogenous IL-22 examined using quantitative RT-PCR. Optimal IL-22 coated nanoparticles will then be used in a chemically induced murine colitis model as well as a spontaneous colitis model to examine the effect on gut inflammation. In addition to assessing histologic inflammation, RT-PCR will be utilized to interrogate pro- and anti-inflammatory pathways as well as oxidative stress pathways. Suitable for: Students pursuing a PhD project with knowledge of molecular biology and basic immunology. Type of Research: Wet lab. 2 RESEARCH AREA / TOPIC Specialist Pain Physician Persistent Pain Service, Division of Rehabilitation CONTACT PERSON - Dr Aston Wan NAME CONTACT EMAIL / aston.wan@health.qld.gov.au PHONE Possible B.Med Sci Projects at MSH Persistent Pain Management Service 1. The effects of culture and socioeconomic difference on the presentation of Chronic Pain. 2. An audit of the effectiveness of interventional pain procedure. 3. Culture difficulties and socioeconomic factors contributing to the effectiveness of pain intervention 4. Predictors of outcomes of chronic pain management. 5. Prevalence of Somatoform disorders in chronic pain patients 6. Functional outcome of mindfulness meditation and Acceptance Commitment therapy 7. Role of physiotherapist in Somatoform disorders. 8. Patient satisfaction in MSH Persistent Pain Management Service. 9. Pain Rehabilitation program – what are patient’s expectation / what do patients find acceptable. 10. Do multiple cancellations affect patient outcomes? Dr Aston Wan MBBCh MA GDMM MClEpid MPainMed MHeadacheMed PCertMedEd FFPMANZCA Director and Specialist Pain Physician Persistent Pain Service, Division of Rehabilitation Princess Alexandra Hospital 199 Ipswich Rd, Woolloongabba, Queensland, Australia, 4102 Ph:+61 7 3176 1901 l Fax:+61 7 3176 3969 l Metro South Health Persistent Pain Management Clinic Level 3, Network House, 57 Sanders Street, Upper Mount Gravatt, Queensland, Australia 4122 Ph:+61 3339 5500 Email: aston.wan@health.qld.gov.au 3 RESEARCH AREA / Cardiac Imaging (Cardiology/Radiology) TOPIC CONTACT PERSON - A/Prof Christian Hamilton-Craig NAME CONTACT EMAIL / PHONE c.hamiltoncraig@uq.edu.au / chamiltoncraig@gmail.com 3139 5226 or 0411 111 980 New Projects as of September 2014 - Comparison Of Sensitivity And Specificity Of "Reference Centre" Versus "Community" Based Coronary Ct Angiography Compared To Invasive Xray Angiography (Medical Student / Honours) - Six Year Follow Up And Outcome Of Cardiac Magnetic Resonance Imaging Detected Left Ventricular Trabeculation Without Non-Compaction In Dilated Cardiomyopathy (Medical Student / Honours) Impact Of Cardiac MRI Results On Management Of Patients Referred To An Advanced Heart Failure Unit: Improvements In Diagnosis And Management - Takotsubo Cardiomyopathy By Cardiac MRI - Use Of SSFP Feature Tracking Post-Processing (Honours/Masters Student) - Comparison Of Tissue Tagging Versus SSFP Feature Tracking By Cardiac Magnetic Resonance (MRT / Masters / PhD Student) Intra-Operative TransOesophageal Echocardiography during Cardiac Valves Surgery with 2D and 3Dimensionl imaging; comparison between Expert and Novice Readers (Medical Student) A/Prof. Christian Hamilton-Craig MBBS, PhD, BMedSci(Hons), FRACP, FCSANZ, FSCCT Staff Cardiologist, Prince Charles Hospital Associate Professor, School of Medicine & Centre for Advanced Imaging, UQ Affiliate Associate Professor of Radiology, University of Washington, Seattle USA Chair, Society of Cardiovascular CT (ANZ), Vice-President ANZCMR 4 A state wide matched case-control study of bilateral sensorineural hearing loss in Queensland’s premature infant population between 2007 and 2011: Aetiological factors and screening (Diagnosis and description of preterm infants with hearing loss detected under newborn hearing screening) Introduction: All babies born in Queensland are screened for hearing loss soon after birth through the Queensland Healthy Hearing, Newborn Hearing Screening Program (Queensland Health). Hear and Say, a program helping children with hearing loss to learn to listen and speak, will work in partnership with Professor David Tudehope to conduct a case control study examining specific aetiological factors for pre-term infants diagnosed with a permanent hearing loss. This study includes a focussed literature review which has helped define the aims and objectives of this project, and ensures the study is novel and does not duplicate already published work. The study has, in 2013-2014 been designed and initiated by a current MBBS 3-4 Honours student from University of Queensland. Applications are called for a volunteer MBBS Year 2 student in 2014, with a view to the successful student continuing on to an Honours program in 2015 and collaborating with the more senior student to complete data gathering, analysis and write-up. The Year 2 student will assist with an ongoing literature review to cover any relevant new literature on this topic, determine current research and identify knowledge gaps. This will be followed by the use of a data extraction tool to complete a retrospective chart review of cases and matched controls to determine contributing factors to the hearing loss and its outcomes and any coexisting features of this population. There are a number of different opportunities for publications emanating from this study. Aims & Objectives: To gain information on the diagnostic process and aetiology and to describe the co-existing features of the population of infants diagnosed with hearing loss through universal newborn hearing screening in Queensland. The outcomes of this study will be used to inform government and decision makers. This study will also develop the Hear and Say Foundation for future outcomes research which will enhance the diagnosis, treatment and counselling for these infants and their parents. Study Outcomes and Significance: This study will make a significant contribution to the knowledge of outcomes for preterm infants with hearing loss. It will be a world-first study in this area. The selection process will favour students with good writing skills, previous publications, prior experience with data extraction or chart reviews. Please apply in writing including your curriculum vitae to: Adjunct Associate Professor Dimity Dornan dimity@hearandsaycentre.com.au 5 RESEARCH AREA or Professional Identity, Intergroup Dynamics and Communication in TOPIC Health CONTACT PERSON - A/Pro David Hewett, Dr Bernadette Watson and Lori Leach NAME CONTACT d.hewett@uq.edu.au EMAIL / PHONE bernadette@uq.edu.au l.leach@uq.edu.au Research Team: David G Hewett (in collaboration with Bernadette M Watson and Lori E Leach) Brief synopsis of our research area: Our research team specialises in research that combines the viewpoints and expertise of medical and social science researchers. Our research includes the examination of intergroup dynamics, the nature of communication in health care, and their effects on quality of health care delivery and patient safety. Uniquely, our team investigates communication and its effects through a social psychological lens. We invoke social identity theory and communication accommodation theory as the frameworks from which to explore professional identity and communication in health care. We are currently finalising the design of a number of small studies we will conduct over the next 36 months. Title of current project: Towards better healthcare: The impact of intergroup communication on patient safety. Duration of the project: Three years Positions open for volunteer experience (from one month to six weeks), Honours, Mphil and PhD For those interested in a taster of research experience with out team, as a volunteer you would assist in the preparation of aspects of studies conducted under our broader research domain. You would gain observer experience in one or more of the research team’s activities. These activities would include participation in research design and study implementation, preparation of ethics applications and literature reviews. Active participation in these activities would be apportioned to the volunteer in line with the successful applicant’s current experience and skill level. For those interested in a higher level of engagement, research higher degree students (including Honour’s students) would take on more responsibility and potentially design a study of their own within the broader research project at a level appropriate to each academic level. Prerequisite skills: Nil. 6 RESEARCH AREA / TOPIC Doctors’ Health e.g. Cancer/Immunity/Primary Care CENTRE/INSTITUTE/SCHOOL Discipline of General Practice, School of Medicine CONTACT PERSON Dr Margaret Kay EMAIL / PHONE m.kay1@uq.edu.au Title: What do patients and carers expect from GPs at the end of life? Description of the project: This project seeks to investigate the experience of compassion satisfaction / fatigue in general practice including general practitioners, practice nurses and/or administration staff. Type of involvement: The project is suitable for an honours project or can be expanded for an RHD student. It is also possible to participate in this project as an extra-curricular experience e.g. summer scholar. Supervisors: Dr Margaret Kay, Discipline of General Practice, School of Medicine, The University of Queensland. Student profile: Summer Scholar, Hons Student, RHD Student More information: If you are interested in research projects at the Discipline of General Practice, please refer to our website: www.som.uq.edu.au/about/academic-disciplines/general-practice.aspx 7 RESEARCH AREA / TOPIC Multi-Morbidity e.g. Cancer/Immunity/Primary Care CENTRE/INSTITUTE/SCHOOL Discipline of General Practice, School of Medicine CONTACT PERSON Dr Margo Lane EMAIL / PHONE m.lane5@uq.edu.au Title: The Evaluation of a Pilot Multi-Disciplinary Student–run Health Promotion Program at the Workplace of Adults with Intellectual Disability (Health and Wellbeing Project). Brief Description: This project will be piloted later this year and will need a formal evaluation. Students from four health disciplines (Medicine, Psychology, Dietetics, Exercise Physiology) will prepare and present information to adults with intellectual disability at their workplace. We will collect pre- and post-activity data from students and participants. We hope to explore student issues including teamwork, knowledge, skills and attitudes towards adults with ID, as well as health literacy and self-efficacy for adults with ID. We are also investigating the feasibility and benefits of brief health promotion interventions in the supported workplace. Type of involvement: The project is suitable for an Honours Student Project Supervisors: Dr Margo Lane, Discipline of General Practice, School of Medicine, The University of Queensland Student profile: Honours Medical Student More information: If you are interested in research projects at the Discipline of General Practice, please refer to our website: www.som.uq.edu.au/about/academic-disciplines/general-practice.aspx 8 RESEARCH AREA / TOPIC Immunology-Human Kidney Research e.g. Cancer/Immunity/Primary Care CENTRE/INSTITUTE/SCHOOL Queensland Institute of Medical Research CONTACT PERSON Dr Andrew Kassianos EMAIL / PHONE Andrew.kassianos@qimr.edu.au / 38453036 Chronic kidney disease (CKD) is the most prevalent chronic disease in Australia. It has been estimated that more than 1.4 million Australians have CKD and these metrics are deteriorating rather than improving, emphasising that our current understanding of the pathogenesis of CKD has not produced effective therapeutic strategies. Tubulointerstitial fibrosis, the hallmark of CKD, is always preceded by inflammation. However, current therapeutics for CKD do not target this inflammatory process. This is due to our poor understanding of the role of inflammatory immune cells in the development of progressive CKD. Our research group has been studying the role of specific epithelial cells in the kidney and how these cells contribute to the disease process and maintain tissue homeostasis at the early stages of disease. We have published novel findings that these cells are able to modulate autologous immune responses at the level of T lymphocytes/B lymphocytes and dendritic cells (Wilkinson et al, NDT, 2011; Kassianos et al, NDT, 2013). We are now expanding these unique clinical findings to investigate the role of dendritic cells and lymphocytes in the disease process. We have developed novel methods to dissociate human disease biopsy tissue and characterise immune-cell subtypes within early and late stage CKD. Using this methodology we have recently described, for the first time in humans, a role for dendritic cells in driving tubulointerstitial fibrosis and thus CKD (Kassianos et al, AJP – Renal Phys, 2013). Opportunities exist for Honours and PhD projects to extend these studies, including: An investigation into the recruitment and retention of inflammatory and pathogenic immune cells within the kidney interstitium. The identification, enumeration and characterisation of lymphocyte subsets (T cells, B cells, NK, NK-T) within human disease kidney tissue. The role of immune cells in clinical transplantation rejection. These projects are innovative as our group was the first to describe that human kidney epithelial cells modulate autologous immune responses and we are currently the world leaders in this field. Furthermore, these projects are conducted in human disease systems in a strategy to accelerate translation of our results into clinical testing. These projects will provide students with exposure to many relevant and broad laboratory techniques, including flow cytometry, immunohistochemistry, molecular biology, western blotting and cell culture. 9 RESEARCH AREA / TOPIC Epidemiology/Gastroenterology CENTRE/INSTITUTE/SCHOOL School of Population Health CONTACT PERSON A/Prof Jolieke van der Pols EMAIL j.vanderpols@uq.edu.au Life-style related risk factors for sessile serrated adenoma Sessile serrated adenomas are a newly discovered type of bowel polyps that may progress to colorectal cancer. These polyps were previously grouped with hyperplastic polyps and thought to be harmless. However, in recent years is has been recognised that sessile serrated adenomas can progress to cancer through the ‘serrated pathway’. Much progress has been made in the understanding of how these polyps are clinically and molecularly different from the more common adenomatous polyps. However, knowledge of the epidemiology and risk factors for sessile serrated adenomas is still very limited. This is due to the fact that these lesions have only recently become recognised and recorded clinically, thus few people have had an opportunity to study these cancer-precursors. To establish the risk factors for sessile serrated adenoma we are currently carrying out a case-control study together with a team of gastroenterologists and clinical researchers who are world-leaders in research of sessile serrated adenoma biology and polyp detection at the Royal Brisbane and Women’s Hospital, The Prince Charles Hospital and UQ School of Medicine. This study focusses particularly on lifestyle-related risk factors including smoking, alcohol intake, physical activity, dietary and other factors. We are recruiting patients who have been diagnosed with sessile serrated adenoma during colonoscopy and compare these with patients with conventional adenoma and persons without bowel polyps. Research opportunities for MBBS students: There are several possible topics for a systematic literature review linked to this research project (depending on your interests and experience), which would be very suitable for an Honours project. Students located outside Brisbane are also invited to apply. Data analysis may also become available. Applications for MPhil projects will also be considered and topics can be tailored to your specific interests. Please contact us if you are interested to discuss further details. 10 RESEARCH AREA Orthopaedics and Sports Medicine or TOPIC CONTACT PERSON - Dr. Manit Arora NAME CONTACT Manit_arora@hotmail.com EMAIL / PHONE Multiple review projects to be lead by undergraduate medical students with a keen interest in orthopaedics and sports medicine. Optional lab component in affiliation with the university. Projects available for review: 1. review the literature on which nutritional supplements are best for which hip fractures and develop a protocol to guide surgeons and geriatricians 2. review the role of various BMPs in the fracture healing process. Can include a lab component through co-operation with major teaching hospital 3. Review literature on SLAP tears and develop a treatment algorithm based on current classification system 4. Review literature on chance fractures in TL spine and develop a treatment algorithm based on the current classification system 11 UQ Diamantina Institute – Student Research Projects http://www.di.uq.edu.au/research-projects Cancer Name Professor Ian Frazer Project Details Associate Professor Brian Gabrielli Dr Graham Leggatt Contact Regulation of effector T cells by the innate immune response Immunotherapy for virus associated skin cancer Cervical cancer control in Vanuatu Phone +61 7 3443 7715 Email emma.lee@tri.edu.au Identifying the molecular basis for defective checkpoints in melanoma. Targeting defective cell cycle responses to ultraviolet radiation and TopoII inhibitors in melanoma. Defining the molecular changes in moles underpinning morphological changes detectable by non-invasive imaging techniques to improve their diagnostic and prognostic ability for early stage melanoma. Trafficking of T cells to cancerous skin Immunotherapy of skin tumours after lymphodepletion T cell function in normal and cancerous skin tissue Phone +61 7 3443 7092 Email briang@uq.edu.au Phone +61 7 3443 6961 Email g.leggatt@uq.edu.au Dr Angus Harding Combining computer models and clinical data to understand, treat and prevent brain cancer Phone +61 7 3443 6926 Email a.harding1@uq.edu.au Dr Michelle Hill Cancer microvesicles as a source of biomarkers and novel target of anti-cancer therapy Systems biology approach to understand lipid raft and caveolin function in health and disease Discovery and validation of novel salivary and blood biomarkers for head and neck cancers using lectin magnetic bead arraymass spectrometry, LeMBA-MS (with Dr Chamindie Punyadeera) NPM functions associated with acute myeloid leukemia (with Dr Kerry Inder) Understanding the molecular basis for the control of squamous differentiation Understanding how these processes are dysregulated during the development of oral and skin cancers Exploiting this knowledge in the development of novel treatments for skin cancers and oral cancer Interrogating chemotherapeutic sensitivity Phone +61 7 3443 7049 Email m.hill2@uq.edu.au Associate Professor Nicholas Saunders Phone + 61 7 344 37091 Email nsaunders@uq.edu.au 12 Identifying novel strategies to treat metastatic osteosarcoma Dr Fiona Simpson Improving patient responses to Cetuximab. Improving patient responses to Herceptin. The role of Girdin in breast cancer metstasis Phone +61 7 3443 6930 Email f.simpson@uq.edu.au Dr James Wells Immunotherapy for the treatment of established skin cancer Requirements for the initiation and treatment of Non-Melanoma skin cancer Immunophenotyping squamous skin cancer Investigating the cytokine microenvironment of squamous cell carcinoma and its precursor lesions Uncovering CD8 T-cell control mechanisms in the skin Exploring the interaction between osteosarcoma tumour cells and lung cells to identify the mechanisms that preferentially drive tumour cells from the bone to the lung. Investigation of the interaction between highly- and poorly-metastatic clonal variants of osteosarcoma with osteoclasts. Tumour-secreted exosomes are emerging mediators of tumourigenesis and metastasis. This project will initially isolate and characterise exosomes from metastatic and non-metastatic OS tumour cells Antibody-drug conjugates in therapy against blood cancers. The effect of chronic stress on immune surveillance and immunotherapy of cancer. Immunosuppressive myeloid cell populations induced by B cell lymphomas. NKT cell and Toll-like receptor-driven therapeutic vaccination against blood cancers. The cancer biology of chromosome instability in a transgenic mouse model Identification of signal transduction pathways that cause chromosome instability Transcriptional regulation of cell cycle genes Development of strategies to specifically target cancer cells with abnormal chromosome numbers Phone +61 7 3443 6983 Email j.wells3@uq.edu.au Targeting the actin cytoskeleton as a strategy for melanoma therapy. Disarming Tumor Escape Mechanisms in Human Melanoma With Epigenetic Modifiers Real-time cell cycle imaging of melanoma cells in vitro and in vivo. Defining the role of Microphthalmiaassociated Transcription Factor (MITF) in melanoma growth by real-time cell cycle imaging. Phone Dr Liliana Munoz Dr Stephen Mattarollo Dr Pascal Duijf Associate. Professor Nikolas Haass Phone +61 (0)7 3443 6929 Email l.munoz@uq.edu.au Phone: +61 7 3443 6985 Email s.mattarollo@uq.edu.au Phone +61 (0)7 3443 6937 Email p.duijf@uq.edu.au +61 (0)7 3443 7087 Email n.haass1@uq.edu.au 13 Associate Professor Kiarash Khosrotehrani Dr Rehan Villani Dr Linda Scott Understanding the role of the underlying dermis in the genesis and progression of basal cell carcinoma Study of epidermal clonal progression towards cancer. Tumour heterogeneity towards metastasis. To understand differences between basal cell carcinoma subtypes at the genomic, transcriptomic and proteomic level Investigating the parallels between hair follicle and tumour niche in skin cancer development Phone +61 7 3443 7088 (UQDI) +61 7 3346 6077 (UQCCR) Email k.khosrotehrani@uq.edu.au Molecular pathogenesis and clonal evolution of the myeloproliferative neoplasms Role of dysregulated JAK/STAT signalling in hematologic malignancies Epigenetic regulation in normal hematopoietic stem cells and their malignant equivalents Molecular basis of leukemogenesis Phone +61 7 3443 7093 Email l.scott3@uq.edu.au Email r.villani@uq.edu.au Autoimmunity Name Dr Antje Blumenthal Project Details Dr Emma HamiltonWilliams Dr Tony Kenna Dr Ray Steptoe Dr Gethin Thomas Innate immune recognition of Mycobacterium tuberculosis and other pathogens Molecular mechanisms of macrophage functions Regulators of immune responses during infection and inflammation Discovery of novel anti-microbials A novel role for the interleukin-2 pathway in humans and mouse models of type 1 diabetes Genetic control of intestinal microflora in type 1 diabetes susceptibility Impaired Regulatory T cell function in type 1 diabetes Transcriptional regulation of inflammation in autoinflammatory diseases Intestinal inflammation in ankylosing spondylitis Innate inflammatory pathways in ankylosing spondylitis. Cellular and molecular pathways of T-cell tolerance Prevention and reversal of autoimmune diabetes Novel methods of gene delivery for tolerance Immunotherapy of allergies and anaphylaxis Exploring T-cell tolerance in B cell malignancies Gene expression profiling in ankylosing spondylitis Identification of novel genes in skeletal disease through large-scale ENU mouse Contact Phone +61 3443 6984 Email a.blumenthal@uq.edu.au Phone +61 7 3443 6989 Email e.hamiltonwilliams@uq.edu.au Phone +61 7 3443 7073 Email t.kenna@uq.edu.au Phone +61 7 3443 6959 Email r.steptoe@uq.edu.au Phone +61 7 3443 7048 Email 14 mutagenesis Novel treatment approaches to prevent joint fusion in ankylosing spondylitis Mechanisms underlying genetic associations in ankylosing spondylitis Understanding the molecular control of dendritic cell function in tolerance Initiation of inflammatory arthritis Rheumatoid arthritis antigen-specific therapy Type 1 (Juvenile) Diabetes Innate Immunity: mouse models and human longitudinal study Use of statins to reduce atherosclerosis in early rheumatoid arthritis Development of ERAP M1 Aminopeptidase inhibitors as a novel class of therapeutics for treatment of Immune-mediated diseases such as Ankylosing Spondylitis (AS), Psoriasis, Inflammatory Bowel disease (IBD). Protein expression and functional studies of ERAP M1 aminopeptidases in Ankylosing Spondylitis (AS), Psoriasis and Inflammatory Bowel disease (IBD). Wanted Alive not Dead: Isolation and analyses of “new” human gut bacteria Bacterial mousetraps: the role of serpins in gut bacteria Professor Ranjeny Thomas Dr Nitish Agrawal Professor Mark Morrison gethin.thomas@uq.edu.au Phone +61 7 3443 6960 Email ranjeny.thomas@uq.edu.au Phone +61 (0)7 3443 7074 Email n.agrawal1@uq.edu.au Phone +61 (0)7 3443 6957 Email m.morrison1@uq.edu.au Genomic Medicine Professor David Evans Professor Matt Brown Next generation sequencing and genome-wide association studies Genetics of common complex traits and diseases Genetics of osteoporosis, eczema and ankylosing spondylitis Using genetics to test whether environmental risk factors cause disease Development of statistical methods for disease gene mapping Genetics of common bone and joint diseases Osteoporosis Interethnic mapping of common human diseases; ankylosing spondylitis, rheumatoid arthritis, schizophrenia ENU mutagenesis and models of musculoskeletal diseases Gene deserts involved in ankylosing spondylitis Genetics of multiple sclerosis Novel gene-mapping approaches using nextgeneration sequencing Phone +61 7 3443 7051 Email d.evans1@uq.edu.au Phone +61 7 3443 7018 Email di.director@uq.edu.au 15 RESEARCH AREA / TOPIC Cancer Epigenetics e.g. Cancer/Immunity/Primary Care CENTRE/INSTITUTE/SCHOOL QIMR Berghofer Medical Research Institute CONTACT PERSON Jason S Lee, Eva Baxter and Frank Gannon EMAIL / PHONE Jason.Lee@qimrberghofer.edu.au Project title: Defining the components of the complexes involved in the cyclical processes that result in gene expression Type of student: Honours/Ph.D Prerequisite skills: Mammalian culture and some molecular biology techniques (Western blotting, PCR etc) would be very useful. Type of research: Wet lab Drs Jason S Lee, Eva Baxter and Professor Frank Gannon Introduction Activation of the estrogen-responsive gene pS2 has demonstrated a requirement for cyclical changes in the DNA methylation of promoter CpGs. The proteins mediating DNA methylation have been discovered, however the identification of DNA demethylases in humans has remained problematic. The recent discovery that DNA methyl groups can be oxidised to hydroxymethyl groups by the TET family of proteins raises a possible mechanism whereby the transcriptionally repressive methyl mark can effectively be removed from promoters. We have demonstrated that DNA methylation and demethylation (Kangaspeska et al., Nature 452, 2008) occurs in a transient cyclical manner. However, detailed relationship between epigenetic state, recruitment of the estrogen receptor and the RNA polymerase and initiation of transcription has yet to be investigated. Hypothesis Epigenetic modifications are important in the expression of estrogen receptor target genes. Aims To determine the crosstalk between epigenetic modifications and gene expression by estrogen receptor. To identify the factors responsible for mediating the epigenetic modifications. Approaches 1. Protein complex purification of the estrogen receptor at target genes 2. DNA methylation analysis by bisulphite sequencing 3. Target validation by Chromatin Immunoprecipitation assays. 4. Gene expression analysis References Kangaspeska, S., Stride, B., Métivier, R., Polycarpou-Schwarz, M., Ibberson, D., Carmouche, R.P., Benes, V., Gannon, F. & Reid, G. (2008) Transient cyclical methylation of promoter DNA. Nature 452(7183): 112-115. Métivier R, Gallais R, Tiffoche C, Le Péron C, Jurkowska RZ, Carmouche RP, Ibberson D, Barath P, Demay F, Reid G, Benes V, Jeltsch A, Gannon F & Salbert G. (2008) Cyclical DNA methylation of a transcriptionally active promoter. Nature 452, 45-50 http://www.qimr.edu.au/page/Students/University_students/Projects/Control_of_Gene_Expression_student_projects/ 16 RESEARCH AREA / TOPIC Cancer Epigenetics e.g. Cancer/Immunity/Primary Care CENTRE/INSTITUTE/SCHOOL QIMR Berghofer Medical Research Institute CONTACT PERSON Jason S Lee and Frank Gannon EMAIL / PHONE Jason.Lee@qimrberghofer.edu.au Project title: Identification of new epigenetic modification targets in breast cancer Type of student: Honours/Ph.D Prerequisite skills: Mammalian culture and some molecular biology techniques (Western blotting, PCR etc) would be very useful. Type of research: Wet lab Drs Jason S Lee, Eva Baxter and Professor Frank Gannon Introduction Chromatin remodeling is by the so called “histone-code” involving various covalent modification of the histones such as acetylation, phosphorylation and methylation has been subject to many studies and their importance is now very well accepted. However, the transcriptional state can also be regulated by several chromatin-associated protein complexes that are either involved in enhancing or fine-tuning of the promoter activity and, of course some of these respond to the altered contexts that arise from the histone, and DNA modifications. In this project we will focus on novel aspects of the histone methylation status and related “off-target” activities of the enzymes involved and their consequences in cellular physiology. Hypothesis Epigenetic modifying enzymes play an important role in regulating breast cancer metastasis through non-histone targets. Aim To discover novel targets of the epigenetic modifiers in by integrating proteomic and high throughput sequencing techniques. Approaches 1. Cellular models and treatments 2. Characterisation of the KMT and the KDM change 3. Promoter methylation analysis 4. Protein complex purification and proteomics 5. Immunoprecipitation assays 6. Characterisation of putative methylation target proteins References Lee et. al., EZH2-Generates a Methyl Degron that is Recognized by the DCAF1/DDB1/ CUL4 E3 Ubiquitin Ligase Complex. Molecular Cell, 48, 572–586, 2012. Lee et. al., Negative Regulation of Hypoxia Response by Induced Reptin Methylation. Molecular Cell. 39, 71-85, 2010. http://www.qimr.edu.au/page/Students/University_students/Projects/Control_of_Gene_Expression_student_projects/ 17 RESEARCH AREA / TOPIC Cancer Epigenetics e.g. Cancer/Immunity/Primary Care CENTRE/INSTITUTE/SCHOOL QIMR Berghofer Medical Research Institute CONTACT PERSON Jason S Lee and Frank Gannon EMAIL / PHONE Jason.Lee@qimrberghofer.edu.au Project title: Elucidation of new epigenetic modifier targets in stem cell differentiation Type of student: Honours/Ph.D Prerequisite skills: Mammalian culture and some molecular biology techniques (Western blotting, PCR etc) would be very useful. Type of research: Wet lab Drs Jason S Lee, Eva Baxter and Professor Frank Gannon Introduction Embryonic stem cells (ESCs) are pluripotent, self-renewing cells that are derived from the inner cell mass (ICM) of the developing blastocyst. Transcription factors (TFs), such as Oct4, Sox2, KLF4 and Nanog (ESC TFs) are critical for establishing and maintaining pluripotent cell identity by collaborating with each other to activate a substantial fraction of the actively transcribed protein-coding and miRNA genes in ESCs. We are particularly interested in expanding our novel description of physiologically relevant consequences of “histone” modifying enzymes on non-histone targets. We will also utilise our Histone-like protein database as previously used to determine potential modification sites on key non histone proteins. Discovery of molecular mechanisms that control ESC pluripotency and self-renewal are important as they are key to understanding development. Because defects in development cause many different diseases, improved understanding of control mechanisms in pluripotent cells may lead to new therapies for these diseases. Hypothesis Based on the functional importance of these ESC transcription factors in regulating gene expression, we hypothesise that the transcriptional activity of ESC TFs are altered by posttranslational modifications resulting in changes in ESC gene expression program, and ultimately affect pluripotency and their ability to self-renew. Aim Determine whether ESC TFs are modified by several classes of epigenetic modifiers. Approaches 1. Protein complex purification and proteomics. 2. Generation of genetically modified cell lines. 3. Functional consequences of ESC pluripotency and self-renewal. 4. Transcriptome and ChIP sequencing analysis. References Loh et. al., The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genetics 38, 431-440, 2006. Chen et. al., Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell 133, 1106-1117, 2008. http://www.qimr.edu.au/page/Students/University_students/Projects/Control_of_Gene_Expression_student_projects/ 18 RESEARCH AREA / TOPIC Cancer Epigenetics e.g. Cancer/Immunity/Primary Care CENTRE/INSTITUTE/SCHOOL QIMR Berghofer Medical Research Institute CONTACT PERSON Jason S Lee and Frank Gannon EMAIL / PHONE Jason.Lee@qimrberghofer.edu.au Project title: Defining the role of epigenetic modifiers in metastatic prostate cancer Type of student: Honours/Ph.D Prerequisite skills: Mammalian culture and some molecular biology techniques (Western blotting, PCR etc) would be very useful. Type of research: Wet lab Drs Jason S Lee, Eva Baxter and Professor Frank Gannon Introduction Chromatin remodeling is by the so called “histone-code” involving various covalent modification of the histones such as acetylation, phosphorylation and methylation has been subject to many studies and their importance is now very well accepted. However, the transcriptional state can also be regulated by several chromatin-associated protein complexes that are either involved in enhancing or fine-tuning of the promoter activity and, of course some of these respond to the altered contexts that arise from the histone, and DNA modifications. In this project we will focus on protein complexes involved prostate metastasis and their consequences in cellular physiology. Hypothesis Epigenetic modifying enzymes play an important role in regulating metastatic potential of prostate cancers through complexing with other proteins. Aim To discover novel targets of the epigenetic modifiers in by integrating proteomic and high throughput sequencing techniques. Approaches 1. Cellular models and treatments 2. Characterisation of the KMT and the KDM change 3. Promoter methylation analysis 4. Protein complex purification and proteomics 5. Immunoprecipitation assays 6. Characterisation of putative methylation target proteins References Lee et. al., EZH2-Generates a Methyl Degron that is Recognized by the DCAF1/DDB1/ CUL4 E3 Ubiquitin Ligase Complex. Molecular Cell, 48, 572–586, 2012. Lee et. al., Negative Regulation of Hypoxia Response by Induced Reptin Methylation. Molecular Cell. 39, 71-85, 2010. http://www.qimr.edu.au/page/Students/University_students/Projects/Control_of_Gene_Expression_student_projects/ 19 RESEARCH AREA / TOPIC Infectious Diseases e.g. Cancer/Immunity/Primary Care CENTRE/INSTITUTE/SCHOOL QIMR Berghofer CONTACT PERSON Denise Doolan EMAIL / PHONE Denise.Doolan@qimrberghofer.edu.au / 3362 0382 Rational vaccine development from genomic sequence information – mining genomic, proteomic and transcriptomic datasets for next generation malaria vaccine development Vaccines are one of the most effective health care interventions for infectious diseases but are still not available for many important public health threats despite decades of research. Malaria is a priority target but conventional approaches to anti-malaria vaccine development, focused on a very limited number of antigens, have thus far failed. During the past decade, the genome, proteome and transcriptome of the Plasmodium parasite, the causative agent of malaria, have been defined. These datasets provide a unique foundation for a new approach to vaccine development but it has not been obvious how to identify the important protective antigens from genomic-based information. Beginning with the full set of open reading frames encoded in the Plasmodium parasite genome, we are pursuing a rational approach to vaccine design for infectious diseases caused by complex pathogens, using malaria as a model. We are taking advantage of recent advances in genomic sequencing, proteomics, transcriptional profiling, bioinformatics, and molecular immunology to choose from the complete set of Plasmodium proteins those most likely to be effective as vaccine targets. A key aspect of our strategy is functional significance as assessed by the capacity of the antigen to be recognized by immune responses in protective human models. We have generated unique datasets of proteome-wide T cell responses and antibody responses to Plasmodium. The focus of this project will be to further characterize these antigens for potential as vaccine candidates by assessing immunogenicity, protective capacity and biological function. In addition to identifying and prioritizing novel antigens for next generation vaccine development, we are integrating these genomic-based datasets to develop metrics associated with protection which can be extended to other complex pathogens for which vaccines are urgently needed. These datasets also provide a unique opportunity to further our understanding of host-parasite relationships and associated phenomenon such as immunodominance. This project is expected to result in significance advances in vaccinology as well as immunology, with important public health outcomes. Applicants must possess a BSc Hons, MSc., MBBS or equivalent with laboratory-based experience in immunology, genomics/proteomics or infectious diseases. Excellent computer, communication, and organisational skills are required. Forward thinking, innovation and creativity are encouraged. http://www.qimr.edu.au/page/Lab/Mol_Vaccinology/ 20 RESEARCH AREA / TOPIC Infectious Diseases e.g. Cancer/Immunity/Primary Care CENTRE/INSTITUTE/SCHOOL QIMR Berghofer CONTACT PERSON Denise Doolan EMAIL / PHONE Denise.Doolan@qimrberghofer.edu.au / 3362 0382 Dissecting the molecular basis of protective immunity to malaria using interdisciplinary approaches Malaria remains a leading public health threat with approximately 40% of the world’s population at risk. The Plasmodium spp. parasite which causes malaria has a complex life cycle and has coevolved with the human host over thousands of years. Protective immunity against malaria can be induced in experimental systems by immunization with the intact parasite, suggesting that a malaria vaccine is feasible. However the development of an effective vaccine has been hindered by the complexities of the parasite and the host, and by our poor understanding of the mechanisms of protective immunity. Animals or humans exposed to Plasmodium typically develop a multi-faceted immune response including antibodies and CD8+ and CD4+ T cell components directed against multiple antigens, but little is known about the fine specificities of protective immunity and how to induce the correct specificities by vaccination. To address this, we are investigating the molecular basis of immunity to malaria, taking advantage of well established rodent models of lethal and non-lethal malaria, a unique controlled humanexperimental blood-stage infection system, and cross-sectional and longitudinal field studies in malaria-endemic areas. In the rodent models, we employ gene deficient and transgenic mice, including cytokine- and cell-deficient lines, reporter lines, and transgenic lines that allow depletion of specific cellular subsets of interest. We have access to state-of-the-art flow cytometry, microscopy and immunohistochemistry facilities as well as cutting-edge molecular based technologies including protein microarrays, gene expression platforms, high throughput sequencing, and bioinformatics. A specific interest is in the field of systems immunology, which differs from reductionist approaches that analyse isolated components of the immune system, by studying the integration of the various components using high throughput molecular techniques combined with mathematical and computational tools. The focus of this project will be to employ cutting-edge molecular technologies to define the critical cells and signalling pathways required for long-term protective immunity against malaria, with an emphasis on the interface between innate and adaptive immunity. Applicants must possess a BSc Hons, MSc., MBBS or equivalent with laboratory-based experience in immunology, genomics/proteomics or infectious diseases. Excellent computer, communication, and organisational skills are required. Forward thinking, innovation and creativity are encouraged. http://www.qimr.edu.au/page/Lab/Mol_Vaccinology/ 21 RESEARCH AREA / TOPIC e.g. Cancer/Immunity/Primary Care Infectious Diseases CENTRE/INSTITUTE/SCHOOL QIMR Berghofer CONTACT PERSON Christian Engwerda EMAIL / PHONE chrisE@qimr.edu.au Immunology and Infection laboratory, QIMR Berghofer We study host immune responses during malaria and leishmaniasis, two deadly parasitic infections. We seek Honours and PhD students. An interest in infectious diseases and immunology is required. Successful candidates will learn flow cytometry, microscopy and various immune assays. Please see http://www.qimr.edu.au/page/Lab/Immunology_Infection/ for more information. 1. Investigating the influence of the gut microbiome on the outcome of malaria and leishmania. Commensal organisms (including bacteria, fungi, viruses, protozoa and archaea) occur in distinct niches within tissue microenvironments throughout the body. They develop an intimate relationship with their host and play an important role in metabolism, tissue development and maintenance, as well as host defence. Although the liver is not colonised by commensals, the functions of hepatic immune cells is likely to be impacted by exposure to microbial ligands and metabolites from the gut microbiome. Both malaria and leishmaniasis stimulate potent immune responses in the liver that can determine the outcome of infection. We aim to examine the influence of the gut microbiome on hepatic immune responses during malaria and leishmania. 2. Characterising the roles of innate lymphoid cells during malaria and leishmania. Innate lymphoid cells are emerging as critical players in early immune responses to infection. They play an important role in maintaining gut epithelial cell barrier integrity, regulating the intestinal microbiota and defence against gut pathogens. However, little is known about their roles in diseases caused by systemic infections, such as malaria and leishmania. Several distinct families of innate lymphoid cells have been identified, based on the expression of certain cell surface molecules and their pattern of cytokine production. We aim to characterise the behaviour of innate lymphoid cells during malaria and leishmania, and establish their roles in anti-parasitic immunity and disease pathogenesis. 3. Identifying epigenetic changes that regulate cytokine production by parasite-specific CD4+ T cells during malaria and leishmania. CD4+ T cells are critical for the control of many intracellular pathogens, including those that cause malaria and leishmania. The pattern of cytokines produced by parasite-specific CD4+ T cells during infection determines whether immunity is established or disease develops. This pattern is influenced by the early interactions between CD4+ T cells and dendritic cells during parasite antigen presentation, and in particular, the local cytokine milieu. A major mechanism for switching on and off cytokine production in cells is via epigenetic modification of gene promoters. We will characterise changes in the promoters of key cytokine genes in antigen-specific CD4+ T cells during malaria and leishmania under various conditions and at different times during disease. 22 RESEARCH AREA / TOPIC Adolescent substance use and misuse e.g. Cancer/Immunity/Primary Care CENTRE/INSTITUTE/SCHOOL Centre for Youth Substance Abuse Research CONTACT PERSON A/Prof. Adrian Kelly EMAIL / PHONE a.kelly@uq.edu.au A/Prof Kelly has several research projects available in the area of family and school problems, health risk behaviours (including substance use and misuse, but also adolescent depression, anxiety, dietary problems, and antisocial behaviour). His work has primarily focused on factors leading to the escalation of problems related to alcohol use, tobacco use, and other drug use. Research projects are available to Masters and PhD students. Some knowledge of widely used statistical packages, such as SPSS or Stata, is desirable. A/Prof. Kelly will assist students in building a working knowledge of these packages should it be needed. Secondary datasets are potentially available through our own Centre and through long standing collaborations with other centres across Australia. The availability of high quality datasets reduces the risks associated with timely collection of data, and A/Prof Kelly has an excellent track record in supporting his students right through to publication of research findings in high level journals. Examples of A/Prof Kelly’s work are available on Research gate: https://www.researchgate.net/profile/Adrian_Kelly2/ 23 RESEARCH AREA / TOPIC Surgery e.g. Cancer/Immunity/Primary Care CENTRE/INSTITUTE/SCHOOL Princess Alexandra Hospital CONTACT PERSON Pallav Shah EMAIL / PHONE pallavshah@ozemail.com.au, 0439726871 Title: Understanding the Genes Responsible for the Development of Bicuspid Aortic Valves (BAV) and Dilated Ascending Aortas.(AAD) Student type: Honors Student Prerequsitive Skills: Dedication and Hard work. Interest in surgery Project Involves: Background: Aortic valve is a left sided valve, which pumps blood from the heart through the aorta to the rest of the body. Usually it has three cusps in 99% of the population. Thus it is called a tricuspid valve. In 1-2% of the individuals, it is bicuspid ( BAV, two leaflets) These patients with bicuspid valve have increased stress during cardiac cycle and thus develop stenosis and regurgitation earlier then tricuspid valves. Further more , it has been shown that bicuspid valves are associated with dilated aorta (AAD, bicuspid aortopathy) BAV together with AAD is a clinical syndrome with poorly understood aetiology. They present at a young age suggesting strong underlying genetic influence . These pathologies lead to heart failure and life threathining emergency like aortic dissections.. Aim: Our aims of the project include 1]To identify the presence of rare exonic mutations in patients with biscuspid aortic valves and aortic aneurysms 2] To evaluate detailed genotype - phenotype relationships using our extensive clinical and imaging records. The research plan involves: 1] recruiting subjects with BAV-AAD, ( 12 patients), 2] obtaining clinical and imaging data (chart review, database review) , 3] performing genetic sequencing , 4] Data collection and statistical analysis, 5] Literature review, 6 ]involvement in writing a publication Importance of the project: -Potential for early screending and disease detection, - Potential for early therapy and prevention of AAD, - Minimize the need for surgery and medical emergencies,- Provide insights into other congenital heart diseases Project area: Clinical: Department of Cardiology and cardiothoracic surgery, Princess Alexandra Hospital Genetic Sequencing: The University of Queensland (School of Medicine, Centre for Clinical Genomics, and Diamantina Institute) 24 RESEARCH AREA / TOPIC ENT / Rhinology e.g. Cancer/Immunity/Primary Care CENTRE/INSTITUTE/SCHOOL RBWH, School of Medicine CONTACT PERSON James Earnshaw / Anders Cervin EMAIL / PHONE james@EarnshawENT.com.au or a.cervin@uq.edu.au Predicting outcome in nasal septal surgery (Honours project) James Earnshaw, Anders Cervin Nasal blockage is common condition affecting more than 10 % of the population. It disrupts sleep and as such causes daytime tiredness and can affect quality of life extensively. There are numerous conditions that can contribute to nasal blockage such as; nasal polyps, turbinate hypertrophy, allergic and hyper reactive disease, but a major factor is the deviated nasal septum. Objective measures aimed at measuring airflow through the nose, or the space within the nasal cavity, are of limited value. As septal surgery is a common procedure any measures to reduce the number of unnecessary procedures would be of great benefit. A literature study involving reviewing Methods to measure nasal airway resistance or space Clinical techniques to assess the nasal airway Systemic workup in nasal blockage The role of BMI in nasal blockage The aim of the literature review is to create a management algorithm in patients with a blocked nose not due to chronic sinusitis nor allergy/hyperreactivity 25 RESEARCH AREA / TOPIC Otolaryngology e.g. Cancer/Immunity/Primary Care CENTRE/INSTITUTE/SCHOOL RBWH CONTACT PERSON Prof Anders Cervin EMAIL / PHONE a.cervin@uq.edu.au Title; Quality of life in chronic sinusitis patients referred to a tertiary ENT center. Type of student? Honours What type of research? Data analysis, literature review Quality of life in chronic rhinosinusitis patients is affected by fatigue, blocked nose, sleep disturbances etc. We have for the last 8 months used a quality of life questionnaire called SNOT-22 to investigate the influence on daily activities. The honors project aim to analyse the available data by creating a data base and using descriptive statistics. Furhermore to compare in the littterature different sinusitis related quality of life instruments. The results will influence the development of a electronic QoL database for chronic sinusitis patients. 26 Projects in the Conjoint Kidney Research Lab, QIMR-RBWH Kidney resident cells modulate migratory T/B lymphocytes and dendritic cells Supervisors: Associate Prof. Ray Wilkinson (ray.wilkinson@qimr.edu.au Ph 33620488) Dr Andrew Kassianos (andrew.kassianos@qimr.edu.au Ph 38453036) Dr Helen Healy (Helen.healy@health.qld.gov.au Ph 38367568) Chronic kidney disease (CKD) is the most prevalent chronic disease in Australia. It has been estimated that more than 1.4 million Australians have CKD and these metrics are deteriorating rather than improving, emphasising that our current understanding of the pathogenesis of CKD has not produced effective therapeutic strategies. Tubulointerstitial fibrosis, the hallmark of CKD, is always preceded by inflammation. However, current therapeutics for CKD do not target this inflammatory process. This is due to our poor understanding of the role of inflammatory immune cells in the development of progressive CKD. Our research group has been studying the role of specific epithelial cells in the kidney and how these cells contribute to the disease process and maintain tissue homeostasis at the early stages of disease. We have published novel findings that these cells are able to modulate autologous immune responses at the level of T lymphocytes/B lymphocytes and dendritic cells (Wilkinson et al, NDT, 2011; Kassianos et al, NDT, 2013). We are now expanding these unique clinical findings to investigate the role of dendritic cells and lymphocytes in the disease process. We have developed novel methods to dissociate human disease biopsy tissue and characterise immune-cell subtypes within early and late stage CKD. Using this methodology we have recently described, for the first time in humans, a role for dendritic cells in driving tubulointerstitial fibrosis and thus CKD (Kassianos et al, AJP – Renal Phys, 2013). Opportunities exist for Honours and PhD projects to extend these studies, including: An investigation into the recruitment and retention of inflammatory and pathogenic immune cells within the kidney interstitium. The identification, enumeration and characterisation of lymphocyte subsets (T cells, B cells, NK, NK-T) within human disease kidney tissue. The role of immune cells in clinical transplantation rejection. These projects are innovative as our group was the first to describe that human kidney epithelial cells modulate autologous immune responses and we are currently the world leaders in this field. Furthermore, these projects are conducted in human disease systems in a strategy to accelerate translation of our results into clinical testing. These projects will provide students with exposure to many relevant and broad laboratory techniques, including flow cytometry, immunohistochemistry, molecular biology, western blotting and cell culture. 27 RESEARCH AREA / TOPIC Respiratory physiology e.g. Cancer/Immunity/Primary Care CENTRE/INSTITUTE/SCHOOL Queensland Children’s Medical Research Institute CONTACT PERSON Dr Dean Mills EMAIL / PHONE d.mills2@uq.edu.au / 07 3636 5578 Title: Lung function in children with airway malacia measured with the forced oscillation and multiple breath nitrogen washout techniques. Background: Patients with airway malacia have softer airways that are an abnormal shape. This results in greater changes in airway diameter during tidal breathing and causes a dynamic collapse of the airways during expiration. The current diagnostic techniques for airway malacia are expensive, invasive and there are issues with anaesthesia, reliability and/or radiation. Alternatives are lacking; but the forced oscillation (FOT) and/or multiple breath nitrogen washout (MBNW) lung function techniques are cost-effective, non-invasive methods that are performed during normal breathing. The FOT provides information on respiratory system impedance; respiratory resistance, an accurate measure of airway resistance; and respiratory reactance, the elastic and inertial properties of the respiratory system. MBNW measures ventilation inhomogeneity and the functional residual capacity. Aim: To compare lung function in children with airway malacia measured using FOT and MBNW to a population of healthy children. Methods: Children aged 3-14 years with airway malacia will have height, body mass, FOT and MBNW measurements undertaken at the respiratory clinic at the Royal Children’s Hospital, Brisbane on a single visit. Significance: The incidence of airway malacia in children is 1 in 2100 and it results in significant expense, morbidity and mortality. Airway malacia clinically presents as wheeze and cough and, as the symptoms are similar to asthma and other respiratory conditions, unrecognised or misdiagnosed airway malacia may also increase morbidity and inappropriate diagnoses. This study will, for the first time, determine whether these non-invasive lung function tests can define the presence of airway malacia in children and, if successful, they will help with future diagnoses and reduce the likelihood of inappropriate investigations and treatments. Type of student: MPhil and Honours. Prerequisite skills: None. Type of research: Clinical research involving the recruitment of participants, lung function measurements and data analyses. 28 RESEARCH AREA / TOPIC Respiratory physiology e.g. Cancer/Immunity/Primary Care CENTRE/INSTITUTE/SCHOOL Queensland Children’s Medical Research Institute CONTACT PERSON Dr Dean Mills EMAIL / PHONE d.mills2@uq.edu.au / 07 3636 5578 Title: Breathing and respiratory muscle recruitment patterns in children measured with structured light plethysmography. Background: Assessments of breathing and respiratory muscle recruitment patterns are vital for the investigation of chronic respiratory disease in children. In clinical practice this is undertaken through visual observation and palpation. For research purposes breathing and respiratory muscle recruitment patterns need to be quantified. However, the current techniques to do this can impede normal breathing patterns or are invasive and/or time consuming. Structured light plethysmography is a novel technique that measures breathing and respiratory muscle recruitment patterns noninvasively and efficiently by projecting a grid of light onto the patient’s chest. This technique, however, is yet to be used in children. Aim: To measure breathing and respiratory muscle recruitment patterns in children with structured light plethysmography. Methods: Healthy children and those with asthma and cystic fibrosis aged 3-17 years will have height, body mass and structured light plethysmography measurements undertaken at the respiratory clinic at the Royal Children’s Hospital, Brisbane on a single visit. Significance: Assessments of breathing and respiratory muscle recruitment patterns are vital for the diagnosis of chronic respiratory disease in children. This study will, for the first time, determine whether structured light plethysmography can determine differences in breathing and respiratory muscle recruitment patterns between healthy children and those with chronic respiratory disease and, if successful, the technique will help with future diagnoses. Type of student: MPhil and Honours. Prerequisite skills: None. Type of research: Clinical research involving the recruitment of participants, lung function measurements and data analyses. 29 RESEARCH AREA / TOPIC Respiratory physiology e.g. Cancer/Immunity/Primary Care CENTRE/INSTITUTE/SCHOOL Queensland Children’s Medical Research Institute CONTACT PERSON Dr Dean Mills EMAIL / PHONE d.mills2@uq.edu.au / 07 3636 5578 Title: The effects of Heliox on exercise tolerance in patients with cystic fibrosis. Background: Cystic fibrosis (CF) is the most common lethal genetic disease in the Caucasian population. Many patients with CF do not engage in regular physical activity due to breathlessness and leg discomfort, secondary to respiratory, muscular and cardiovascular limitations. Patients with chronic obstructive pulmonary disease (COPD) have similar exercise limitations to those with CF. Previous research has demonstrated that when patients with COPD breathe a mixture of 21% oxygen and 79% helium (Heliox) the duration that they can exercise for increases by approximately 50%. Heliox improves exercise tolerance in patients with COPD by reducing breathlessness and leg discomfort, secondary to reductions in respiratory, muscular and cardiovascular limitations. Whether Heliox improves exercise tolerance in patients with CF is unknown. Aim: To determine whether Heliox improves exercise tolerance in patients with CF. Methods: Child and adult patients with CF will undertake 3 exercise tests. The first will be a maximal incremental test to determine peak exercise capacity. During the second and third tests, patients will exercise for as long as possible at 80% of their maximum exercise capacity whilst breathing either room air or Heliox. Significance: Maintaining high levels of physical activity is important in the management of CF. However, due to the heightened breathlessness and leg discomfort during exercise, many patients remain inactive. This causes further body deconditioning and leads to further inactivity. If exercise tolerance is improved, then Heliox may be used as a therapeutic aid to improve adherence to exercise training programmes. Regular physical activity in patients with CF slows the progressive decline in lung function, increases quality of life and, ultimately, increases life expectancy. Type of student: MPhil and Honours. Prerequisite skills: None. Type of research: Clinical research involving the recruitment of participants, exercise testing, lung function measurements and data analyses. 30 RESEARCH AREA / TOPIC Respiratory physiology e.g. Cancer/Immunity/Primary Care CENTRE/INSTITUTE/SCHOOL Queensland Children’s Medical Research Institute CONTACT PERSON Dr Dean Mills EMAIL / PHONE d.mills2@uq.edu.au / 07 3636 5578 Title: The influence of experimental factors on respiratory impedance measured with the forced oscillation technique. Background: The forced oscillation technique (FOT) is a non-invasive lung function technique that is used in the investigation of chronic respiratory disease. The FOT provides information on respiratory system impedance; respiratory resistance, an accurate measure of airway resistance; and respiratory reactance, the elastic and inertial properties of the respiratory system. We have recently developed a variation of this technique called the wave-tube FOT that can be used to dynamically “track” changes in respiratory impedance with air flow and lung volumes. How the results of the wave-tube FOT are influenced by experimental factors such as breathing frequency, lung volumes, breath duration, heart rate, neck position and the ingestion of food is unknown. Aim: To examine the influence of experimental factors on respiratory impedance measured with the FOT. Methods: Healthy adults will have height, body mass and FOT measurements undertaken at the respiratory clinic at the Royal Children’s Hospital, Brisbane over 3 visits. Significance: The FOT is a non-invasive lung function technique that is used in the investigation of chronic respiratory disease. The wave-tube FOT can dynamically “track” changes in respiratory impedance with air flow and lung volume either those associated with tidal breathing or with deep inspiration. Within-breath tracking of respiratory impedance is a promising tool for the investigation of chronic respiratory disease, but the influence of experimental factors that may occur in clinical practice or research is unknown. Type of student: MPhil and Honours. Prerequisite skills: None. Type of research: Clinical research involving the recruitment of participants, lung function measurements and data analyses. 31 RESEARCH AREA / TOPIC e.g. Cancer/Immunity/Primary Care CENTRE/INSTITUTE/SCHOOL CONTACT PERSON EMAIL / PHONE Cancer and Primary health care PA-Southside Clinical School A/Prof Jennifer Martin (PA-Southside Clinical School) A/Prof Patricia Valery (Menzies School of Health Research -Brisbane) j.martin4@uq.edu.au tel 3176 5663 Patricia.Valery@menzies.edu.au tel 07 3309 3418 Improving systems and quality of cancer care in Aboriginal and Torres Strait Islander primary health care settings Chief investigators: P Valery, G Garvey, R Bailie, E Walpole, J Adams, D Williamson, J Martin Improving the coordination and continuity of care from cancer diagnosis through to management of cancer is seen as an important step for improvement in the health of the increasing numbers of Indigenous Australians with cancer. Gaps in knowledge exist about Indigenous people with a cancer and their use of health services for their cancer in the Primary Health Care (PHC) setting. The project aims to investigate: 1. which systems are in place to identify Indigenous cancer patients in the PHC setting 2. if required report on how these systems or processes can be improved; 3. to examine the patterns of care of Indigenous cancer patients at the PHC level (mixed methods will be used with medical chart reviews and qualitative interviews about the follow up and coordination of care of Indigenous cancer patients between the sectors); and 4. to develop an audit tool for cancer care with a particular focus on culturally appropriate support, management of comorbidities, follow up and communication between the tertiary health system (major cancer treating hospitals) and the PHC system. Within this project there are sub-studies that are available for volunteers, Honours, MPhil or PhD students. A small involvement in this project (e.g. medical chart reviews, systematic literature review on a topic related to this project) will be suitable for ‘honours’ or ‘volunteer’ students, while a large involvement (e.g. develop an audit tool for cancer care) could be suitable for a MPhil or PhD project (exact topic and scope to be discussed further depending on experience or interest of the application). The student will be jointly supervised by A/Prof Patricia Valery and A/Prof Jennifer Martin. 32 RESEARCH AREA / TOPIC Breast Cancer Metastases e.g. Cancer/Immunity/Primary Care CENTRE/INSTITUTE/SCHOOL Queensland Institute of Medical Research CONTACT PERSON Dr Adrian Wiegmans EMAIL / PHONE adrian.wiegmans@qimrberghofer.edu.au We are looking for H1/H2A honours students to begin a PhD in 2014 on any of our “translational” projects focussed on metastatic breast cancer. Deciphering the molecular mechanisms of metastasis to design new-targeted therapies for breast cancer. The transformation of normal breast tissue to tumor requires the accumulation of mutations, which is readily achieved by deregulation of DNA repair pathways. We found that metastatic breast cancers have high levels of the DNA repair protein RAD51. Metastatic breast cancer represents a subtype that has poor clinical outcome and RAD51 contributes to this. We have determined that reducing RAD51 levels in aggressive breast cancers results in reduced metastatic growth and sensitivity to chemotherapy. RAD51 supports metastasis via a role in stabilizing cancer genomes however RAD51 also augments metastatic potential through other mechanisms. These include changes in actin dynamics and changes in gene metastatic expression profiles via mechanisms that have yet to be fully elucidated. Outcomes from these analyses will provide new potential clinical targets in treating metastatic breast cancer. Individual research projects for developing new therapeutic targets will have a focus around one of the following models; The chemistry of small molecule inhibitors: We are currently in early stage development of small molecule inhibitor library and will need to screen the compounds using various cell biology techniques to establish efficacy of activity against breast cancers. Actin dynamics and metastasis: We find that DNA repair proteins affect actin dynamics, cell morphology and thus the migration and invasion properties of cancer cells. This determines the metastatic potential of the cancer and could be targeted to inhibit metastatic spread of cancer. Transcriptional regulation of metastasis: DNA repair proteins also change the profile of pro-metastatic gene expression via unknown mechanisms. The ability of DNA repair proteins to bind DNA and simultaneously bind transcription factors, mean they have the capability to direct gene expression. This is a new function for this class of proteins. Animal models of metastasis: We are developing new models of metastasis to test new anti-metastatic drugs developed in the lab. We are looking to mimic human diseases, with spontaneous metastasis of breast cancer to specific organs. 33 School of Population Health A systematic review and meta-analysis of clozapine for treatment refractory schizophrenia Clozapine is the most effective treatment for schizophrenia for people who have failed at least two trials of other antipsychotic agents and has been shown to reduce psychotic symptoms, reduce rehospitalisation, reduce overall premature mortality and improve treatment adherence, sociooccupational functioning and quality of life. Clozapine has the potential to cause significant adverse drug effects (ADRs), including neutropenia, agranulocytosis, myocarditis, cardiomyopathy, seizures, metabolic syndrome, hypersalivation, enuresis, obsessive compulsive symptoms, constipation and ileus. A choice to start a person on clozapine must be an informed balance between the efficacy of the treatment and the potential for ADRs. There has been no recent systematic review and meta-analysis comparing clozapine to other antipsychotics for people with treatment refractory schizophrenia to help guide clinician choice. We propose to conduct a systematic review and meta-analysis of clozapine for treatment refractory schizophrenia. Professor Steve Kisely and Dr Dan Siskind, clinical academic psychiatrists based at the Princess Alexandra Hospital, are coordinating this project. Professor Kisely has extensive experience with meta-analyses including work with the Cochrane Collaboration. Tasks for a medical student, under the supervision of Professor Kisely and Dr Siskind, would include: - Systematically reviewing the literature on the efficacy of clozapine for treatment refractory schizophrenia - Selecting relevant articles from the literature - Extracting relevant data from included articles - Working with Prof Kisely and Dr Siskind to run a meta-analysis - Assisting with writing a draft manuscript for submission to a peer-reviewed journal. This project would be ideal for a medical student with an interest in learning how to systematically review the literature. Publication of this project in a peer reviewed journal is expected. Prior experience of literature reviews and/or mental health is not essential. For more information, contact Dr Dan Siskind dan_siskind@qcmhr.uq.edu.au or Prof Steve Kisely s.kisely@uq.edu.au 34 Research Assistant The Inflammatory Bowel Disease Research Unit at the Royal Brisbane and Women’s Hospital (RBWH) and Queensland Institute of Medical Research, conducts clinical, genetic and epidemiological research into Crohn’s disease and ulcerative colitis. Applications are invited for a Research Assistant to review and collect data for a natural history and genetics study which aims to elucidate the causes of IBD. The successful applicant will have a strong work ethic and keen attention to detail, and ideally will have experience in data entry (Microsoft access). This position would provide an ideal opportunity for a motivated student with an interest in clinical research methods to gain practical experience in research study design, data collection, data analysis and manuscript preparation. This position will be based at the Royal Brisbane and Women’s Hospital in Herston. On an ongoing basis the position will require a commitment of 8 hours per week, (flexible working hours if needed) . Over the university summer holiday the position will require a commitment of 40 hours per week. Data collection work will be renumerated, rate appropriate to experience. (Probably around $20 per hour). PRIMARY RESPONSIBILITIES Managing systematic collection of medical information through review of hospital charts and electronic records Entering research data accurately, and maintaining an accurate database through careful auditing and updating of data Liaise with key people in the Queensland health system including pathologists, gastroenterologists, surgeons, general practitioners and hospital administrators to obtain clinical data on on consented patients with Inflammatory Bowel Disease. Assist with data analysis and preparation of papers for publication in international scientific and medical journals KEY SELECTION CRITERIA (Qualifications, Experience, Skills and Abilities) Essential An interest in inflammatory bowel disease and some familiarity with medical concepts relevant to gastrointestinal illnesses Excellent organisational and time management skills, and keen attention to detail Demonstrated ability to use Microsoft Access database applications Commitment to maintain participant privacy and confidentiality Desirable Ability to work independently but also to fit into a project team Knowledge of statistical methods and experience using statistical programs such as SPSS and R Forward your Expression of Interest briefly addressing the above criteria, along with a copy of your CV, to James_Irwin@health.qld.gov.au by 11th October 2013. 35 QIMR Berghofer Supervised by Dr Kate Markey and Prof Geoff Hill, QIMR Berghofer The Anatomy of Graft-versus-host disease Bone marrow transplantation, used as curative immunotherapy for haematological malignancy, is fraught with immunological complications, namely graft-versus-host disease (GVHD) and chronic immune insufficiency which results in opportunistic infection in transplant patient. Central to GVHD pathogenesis is (1) gut damage by pre-transplant chemotherapy and radiotherapy, (2) activation of donor T cells after they are transplanted into the recipient, and (3) subsequent T cell proliferation, cytokine production, and host tissue apoptosis. This results in a clinical syndrome which primarily damages skin, liver and further destroys already fragile gut tissue. Importantly, the lung can be a target organ for both acute and chronic GVHD, and patients who experience lung GVHD We are developing tools in the lab that have allowed us to gain insight into the anatomy of GVHD, and these include: green-fluorescent proteins in various cell types so we can ‘find’ cells in various organs after transplant Firefly luciferase expressing cells (eg donor T cells) that we can track via a live animal imaging system (Xenogen) and therefore follow T cell expansion over time However, there are unsolved questions regarding the timing and location of many important immune interactions after transplant (eg, antigen presenting cells and T cells, recipient gut tissue and donor T cells, donor T cells and residual recipient cells) and there are new tools available at QIMR (eg the Photonimager instrument which allows CT scanning and concurrent fluorescent imaging of live animals) which will be critical in answering these questions. The proposed student project will have the following aims: Establish the parameters for CT scanning recipient animals after transplant to monitor development of GVHD, particularly in the gastrointestinal tract and lung Optimize imaging systems for live animal imaging using injected or ingested near-infrared fluorescent dyes Establish near-infrared based assays for measuring local host-tissue damage (eg, local inflammatory marker release, local apoptosis) After successful assay development, use these new assays in transplant systems to gain new insights into GVHD biology. The student/s successful in applying to work in the lab will be well supported within a group of motivated scientists, under the supervision of Prof Geoff Hill. Aspects of this project could be completed by a talented honours student, or expanded to form the basis of an MPhil or PhD project for the appropriate candidate. For more information contact: Kate Markey | NH&MRC Clinical Training Fellow | Bone Marrow Transplantation Laboratory |The Queensland Institute of Medical Research | Phone: +61 7 3845 3773 | Fax: +61 7 3845 3509 |Email: kate.markey@qimr.edu.au 36 School of Pharmacy and Institute for Molecular Biosciences Project: Using toxins to understand the mechanisms of pain Toxins have evolved in plants, animals and microbes as part of defensive and/or prey capture strategies, and have proven to be invaluable research tools as well as providing leads for potential new therapies. Many venoms and toxins are painful, and this has been instrumental for our understanding of the mechanisms involved in pain. For example, the active component of “hot” chilli peppers, capsaicin, has led to the identification of TRPV1 as a putative analgesic target in peripheral pain sensing neurons. In addition, a surprising number of toxins have been found to be highly selective for a diverse range of mammalian channels and receptors associated with pain signalling pathways. Such toxins may find applications as novel analgesics, as exemplified by the frog alkaloid epibatidine and the conotoxin ziconotide, both of which are several hundred times more potent than morphine. We have a variety of projects for students interested in toxins and pain mechanisms, relating to the identification and characterization of toxins from plants, ants, fish and cone snails with activity at peripheral pain-sensing neurons. CONTACT: Dr Irina Vetter School of Pharmacy and Institute for Molecular Biosciences The University of Queensland i.vetter@uq.edu.au 37