This year we received twenty-nine fellowship submissions by our deadline consisting of 20 training fellowships (clinical); 5 postdoctoral fellowships (non-clinical) and 4 senior fellowships (non-clinical).
Following full external review of ALL applications via the Research Grants Sub-Committee and External Referees, ten applications were short-listed for interviewing (6 training; 3 postdoctoral and 1 senior) based upon scientific merit. Interviews were undertaken by a panel (selected from the Sub-Committee), following which five applications were recommended for funding.
Current holders of active research and innovation grants were invited to submit a PhD studentship application, seven applications were received and following a review by the Research Grants Sub-Committee two were recommended for funding.
All seven recommended awards were subsequently endorsed by the Board of Trustees, totaling new research commitments in this round of £910,228.
Success rate for fellowships: 17%
Success rate for studentships: 29%
PDF1/2010 Dr Barry Denholm, University of Cambridge, £177,147 over 36 months
“The insect nephrocyte as a model for exploring the role of CD2AP in the pathogenesis of nephrotic syndrome”.
Understanding human kidney disease using the fruitfly as a simple model.
Nephrotic syndrome is a severe kidney disease in which excessive amounts of blood protein leak into the urine because the specialised filtration barrier that would normally prevent this leakage breaks down. This study will investigate a key component of the barrier called CD2AP, asking how it normally functions in the kidney, and determining how its malfunction leads to nephrotic syndrome. We will use the filtration barrier in the fruitfly kidney as a model because it will allow us to manipulate the CD2AP gene and observe the effects of these changes easily. This is not possible in human patients.
TF9/2010 Dr Enric Vilar , Lister Hospital, £81,256 over 18 months
“Energy expenditure in chronic kidney disease: relationship to dialysis requirements.”
How much energy do patients with kidney failure use? Does this relate to how much dialysis patients need?
The kidney removes metabolic waste-products. In patients with kidney failure it seems likely that amount of dialysis should be related to metabolic rate and hence energy use. Presently, dialysis dose is adjusted to body water which may give too little dialysis in some patients.
Kidney patients may use energy differently to normal individuals and have different nutritional requirements. We need simple tools to calculate their calorie needs.
We will measure energy requirements by comparing oxygen content of air breathed in and out. We will measure physical activity levels using questionnaires. This information will produce equations which can predict metabolic rate in renal failure. We can then assess whether adjusting dialysis dose to energy expenditure produces better outcomes.
PDF5/2010 Dr Danielle P Cavalcante, University of Cardiff, £157,368 over 36 months
“Mechanisms by which nephritic factors cause renal failure.”
Mechanisms by which the immune system attacks the kidney
Complement is a part of the immune system responsible for killing bacteria. Because complement can also damage our own tissues, it is tightly controlled in our bodies. Usually control works well, complement is activated only where needed to kill bacteria, and is then switched off. Some individuals have a protein in blood, called ‘NeF’, which prevents complement switch-off. As a consequence, complement escapes control and attacks the kidney and other tissues. I will identify and purify individual NeF and thoroughly characterise how they work. This information will tell me why the kidney is attacked and how to stop this happening.
TF13/2010 Dr John Waters, Addenbrooke’s Hospital, £203,706 over 36 months
“A 3-dimensional mesangial and glomerular endothelial cell co-culture to define the role of TGF beta/Bone morphogenetic proteins in glomerular disease”
“A study into the differences in the way different types of kidney cells talk to and affect each other in health and in kidney disease and to identify how this may be prevented or treated”
This project will involve growing two types of kidney cells within a protein gel that models their normal growth environment, allowing interactions in 3-dimensions mimicking what they do within the kidney. The interaction of these cells (by direct contact and by signalling molecules they send to each other) is key to a healthy kidney. The gel system will allow this dynamic interaction to be studied closely and allow the signalling molecules to be manipulated to the deranged pattern seen in kidney disease to provide information of why these renal diseases occur and how they may be prevented or treated.
TF1 2010 Dr James Fotheringham, Sheffield Kidney Institute, £169,624 over 36 months
“Measuring quality and driving change in renal services.”
THE IMPACT OF PRE-EXISTING DISEASE AND THE LOCATION OF CARE IN PATIENTS ADMITTED WITH KIDNEY FAILURE
Patients with kidney failure have high levels of pre-existing health problems (co-morbidity). Variation in outcomes (e.g. hospitalisation, death) amongst such patients is often blamed on differences in co-morbidity. We will combine data from kidney centres reported to the UK Renal Registry with data reported to the NHS from English hospital Trusts. This will allow us to describe hospitalisation, measure the performance of English renal centres with a view to improving quality, and find out whether patients with kidney failure do better if admitted to hospitals with renal services. We will also study procedures and practices and their effect on outcomes.
ST2/2010 Prof. Moin Saleem, Southmead Hospital, £58,607 over 36 months
“Dissociation of CD2AP from the slit diaphragm leads to transcriptional changes in WT1, causing podocyte phenotypic change.”
Investigation of the role of the kidney proteins ‘CD2AP and WTIP’ in health and disease.
The kidney cleans the blood via a filtration process. In many kidney diseases, this process is disrupted, allowing albumin and other proteins to escape into the urine. The kidney’s filters consist of two cell types. One of these cells is called the podocyte, and they contain a protein CD2AP defects in which are known to cause kidney disease. Our understanding of the function of CD2AP remains poor. We aim to investigate the role of CD2AP and its binding proteins WTIP in both healthy and diseased kidney models. This information is important for the development of new treatments for kidney disease.
ST1/2010 Professor Robert Unwin, University College of London, £62,520 over 36 months
“Phosphatonins and postprandial regulation of serum phosphate levels: a potential role in preventing phosphate overload and its adverse effects.”
Exploring the role of the intestinal-renal axis and potential contribution of phosphatonins in phosphate balance in chronic kidney disease
CKD is associated with increased deposition of calcium in arteries, causing them to harden. The high blood levels of phosphate that occur commonly in CKD patients may underlie this process.
By exploring the regulation of phosphate by proteins called phosphatonins, which act on the kidney and gut, this study may identify new therapeutic approaches to reduce premature vascular hardening, and decrease the high risk of cardiovascular disease in CKD patients.
