RESEARCH PROJECT AND INNOVATION AWARDS - JUNE 2014
We received 78 applications in this year’s research grant round (62 Research Projects
and 16 Innovation).
All applications underwent normal peer review via the full Research Grants Committee
(RGC) and External Referees. Forty-four applications (38 research projects and six
Innovation) were short-listed for discussion at the June RGC meeting based upon
scientific merit.
Following discussion the full Research Grants Committee recommended two Innovation
and 12 Research Project applications for funding. These decisions were subsequently
endorsed by our Research Strategy Committee and Board of Trustees.
Total awarded: £2,091,977
Overall Success rate: 18%
Details of the awards made:
Research Project Awards
Dr Qihe Xu at The Rayne Institute, Kings College London
£200,000 over three years
Title: MiR-acles in collectin_g ducts underlie albuminuria-induced renal fibrosis
Heayy proteinuria is an independent indicator of poor prognosis in patients with
chronic kidney disease, which affects millions of people worldwide. We have found that
heavy proteinuria suppressed vitamin A activity in a specialised tvpe of renal tubules
that span the whole kidney. In these cells, vitamin A activity was indispensible for the
expression of three anti-scarring small molecules. This study will define the
mechanisms of molecular interactions between proteinuria and activated vitamin A and
roles for molecules causing and inhibiting scarring in heavy proteinuria-induced
chronic kidney failure. Harnessing the findings of this study, novel preventive
strategies will be proposed.
Dr Matthew Bailey at the University of Edinburgh
£124,372 over three years
Title: The role of endothelin-1 in the renal handling of salt in diabetic mellitus
We want to understand why the kidney cannot effectively excrete salt from the body in
diabetes, and how this affects blood pressure. We propose that the problems in salt
excretion are related to abnormalities in a powerful hormone called endothelin-1,
which can affect renal blood vessel and tubule function. Diabetes is the commonest
cause of chronic kidney disease and endothelin receptor blocking drugs may be
beneficial in patients with diabetic renal disease. This work will help understand the
influence of this hormone and of these drugs on kidney function and blood pressure.
Dr Detlef Bockenhauer at the Institute of Child Health, University College London
£120,085 over two years
Title: Understanding the mechanism of nephrocalcinosis in FAM20A disease
Kidney stones are a painful experience, which endanger kidney function.
Approximately 1 0% of the population will be affected by it at some point in their lives.
The majority of stones contain calcium. In most patients it is not well understood, why
and how the calcium deposits developed in the kidney and treatment focuses on
removal of the stones, rather than prevention. We have investigated a rare inherited
disorder called Amelogenesis lmperfecta (abnormal teeth) and Nephrocalcinosis
(calcium deposition in the kidneys). We identified the underlying genetic cause and now
propose to investigate, how mutations in this gene lead to calcium deposition.
Dr Mark Dockrell at the South West Thames Institute for Renal Research, St Helier
Hospital
£142,052 over three years
Title: The CCN3/CCN2 axis in human tubule epithelial cells and its implication for
tubulointerstitial fibrosis
Many functions in the body are regulated by equilibrium of forces pulling in opposing
directions. Often disease occurs when there is disequilibrium. For years people have
been looking for Ying/Yang molecules in the kidney where an imbalance may explain
the development of kidney disease. CCN2 is a molecule involved in the scar forming
process of fibrosis, particularly in the diabetic kidney. Recently another molecule has
been identified that may be the anti-fibrotic counterbalance to CCN2; CCN3. We wish to
identify whether CCN3 can limit scarring in around the kidney tubule by studying
human kidney cells. Hopefully, this work will point towards a new therapeutic approach
for kidney disease.
Professor Albert Ong at the University of Sheffield
£90,021 over three years
Title: Prostaglandin receptor blockade for the treatment of Autosomal Dominant
Polycystic Kidney Disease (ADPKD)
ADPKD is the most common genetic kidney disease. In half of all ADPKD patients,
kidney function is progressively lost over a number of years leading to kidney failure.
Currently there are no effective ways of predicting, halting or slowing this process.
A key molecule central to the rate at which cysts can expand and grow is called cyclic
AMP (cAMP). An important family of factors known to activate cAMP signalling in the
kidney are called prostaglandins. The recent development of specific and potent
prostaglandin receptor blockers provides a unique opportunity to explore their role as
new treatments for ADPKD.
Dr Timothy Bowen at Cardiff University
£198,104 over three years
Title: Analysis of urinary microRNAs as biomarkers for acute kidney injury
Acute Kidney Injury (AKI) is a common health problem worldwide and severe AKI is
associated with high rates of in-hospital mortality. Existing AKI biomarkers, factors that
can be measured to monitor disease status, do not allow accurate prediction of AKI
progression or recovery. MicroRNAs are a recently discovered family of molecules for
which we have developed methods to detect reproducibly in urine samples. In this
study, we propose to measure target microRNAs in urine samples collected from AKI
patients during AKI recovery, or failure to recover. By these means we will identify
effective, non-invasive, urinary microRNA biomarkers to predict likelihood of AKI
progression.
Professor Bruce Hendry at King’s College London)
£199,657 over three years
Title: Study of inhibition of T-type calcium channels as a potential renal therapy
Kidney disease often arises from abnormal cell growth in the filtering units of the
kidney. Patients who show these changes include those with common diseases such as
diabetes and lgA nephropathy. We have evidence that a new type of drug known as a
selective T-tvpe calcium channel (TTCC) inhibitor may benefit these patients and reduce
kidney damage.
This project is designed to provide clear evidence as to the likely benefits of these
agents to decide if clinical trial study in patients is worthwhile. The work will use cell
experiments and preclinical animal models of kidney disease. If this project succeeds
then there is a clear track to study in man.
Professor Nigel Brunskill at the University of Leicester
£175,128.87 over three years
Title: Endothelial inorganic phosphate signalling to Tropomyosin: A molecular
basis for generation of acutely pro-coagulant endothelial microparticles in
uraemic cardiovascular disease
Disease of the heart and blood vessels is the commonest cause of death in kidney
patients, partly because of increased blood clotting. In kidney disease, particles called
microparticles break off the surface of blood vessels and increase clotting. The high
concentration of phosphate in patients' blood may increase microparticle formation. We
aim to study this by:
1) Adding phosphate to blood vessel cells cultured in the laboratory to see how this
affects signals within the cells which trigger microparticle formation
2) Changing blood phosphate levels in rats with kidney disease to see whether
microparticle numbers change, and whether signals in the blood vessel cells are
the same as those in cells cultured in the laboratory.
Dr Jonathan Barratt at the University of Leicester
£191,121.35 over three years
Title: The role of microRNAs in renal interstitial fibrosis and scarring in lgAN
lgA Nephropathy (lgAN) is a type of kidney disease that commonly causes kidney
failure and the need for dialysis or a kidney transplant. Kidneys work by filtering blood
to remove all the waste products the body doesn't need and producing urine. In lgAN a
blood protein called immunoglobulin A (lgA) is deposited in the filters of the kidney
(these are called glomeruli) causing them to become inflamed and damaged.
Understanding the route which starts with the lgA getting caught up in the glomeruli
and ends with kidney damage will help to identify new and more effective treatments
for this common disease.
Dr Matthias Eberl at Cardiff University
£199,218 over two years
Title: Rapid detection of infection and improving survival in dialysis patients: the
role of unconventional T-cell driven inflammatory responses
Infection has detrimental consequences in dialysis patients. However, correct
identification of infection with standard techniques is slow and inaccurate, leading to
suboptimal patient management, overprescription of broad-spectrum antibiotics and
the spread of multidrug-resistant ‘superbugs’. Our research aims to develop novel
diagnostic tests that can be used at the point of care to rapidly and accurately identify
the cause of infection, and ultimately to improve treatment. This involves the need to
better understand how bacteria are detected by specialised types of immune cells at
the site of inflammation, and how this contributes to infection clearance but also to
collateral tissue damage.
Dr Richard Coward at the University of Bristol
£160,748 over two-and-a-half years
Title: Neuropeptide Y, the podocyte, and kidney disease
An important role of the kidney is to act as a sieve and prevent protein leaking into the
urine. A filter called the glomerular filtration barrier, of which a cell called the podocyte
is extremely important, achieves this. We now have evidence that a molecule called
Neuropeptide Y is found in the podocyte and think it is important for keeping the
filtration barrier healthy. We intend to study this in detail and hope it will result in new
treatments being developed to prevent the loss of protein into the urine and ultimately
reduce the number of people developing kidney failure.
Dr Rachel Lennon at the University of Manchester
£141,208 over two years
Title: Interrogating basement membrane composition and organisation to
understand disease mechanisms in Alport Syndrome.
A scaffold of matrix proteins supports the cells of the glomerular filters and this
scaffold is abnormal in AI ort syndrome. The glomerular cells produce the proteins that
make up the scaffold, however we do not fully understand how this process is
regulated or altered in disease. In this study we will investigate, for the first time,
changes in the molecules that make up the scaffold using proteomics and relate these
changes to the structure of the scaffold using powerful microscopy. This study has
great potential to find new targets, which could help to develop treatment for children
and adults with glomerular disease.
Innovation Awards
Dr Emma Watson at the University of Leicester
£11,300 over one year
Title: A new model to investigate muscle wasting in human CKD
People that have chronic kidney disease very often find that their muscles get weaker
and smaller - especially the muscles in the legs, which is an important consequence of
the disease and means that people find everyday activities like walking get a lot harder.
We do not yet fully understand why or how this happens or whether it can be slowed
down or reversed. This area has been researched before, but only in animals, not
human CKD patients. We proposed to grow muscle from CKD patients in the laboratory
to try to better understand how CKD causes people to lose muscle.
Dr Alice Smith at the University of Leicester
£38,961.88 over one year
Title: Development of a self-management programme to increase physical activity
behaviour in patients with chronic kidney disease
People with kidney disease have an increased risk of heart disease and other health
problems. Regular exercise can be very beneficial for their health and wellbeing, but
most lead inactive lives. Our previous research shows that many kidney patients would
like to take up suitable exercise, but that they need help, advice and support to do so.
In this project, we will work with patients and expert healthcare professionals to create
and test a programme to help kidney patients:
- understand about the role of exercise in kidney disease;
- -make and carry out a realistic plan to become more active in their daily lives.