There are almost four million people in the UK affected by chronic kidney disease (CKD), a silent and progressive kidney damage for which there is no cure. Without a biopsy it is hard to categorically diagnose different CKD-types and identify patients at risk of progressing to kidney failure without tracking them for many months. This also stops pharmaceutical companies from testing new medicines due to long trials. Molecules able to signal early changes in disease progression, proteins known as “progression biomarkers”, are needed not only to improve the chances to cure patients but also to shorten the time to test new drugs. Urine offers a direct readout from the diseased kidney, and as such is an excellent bio-fluid for CKD biomarkers. Despite this, studies analysing urine have been unsuccessful due to a predominance of abundant plasma proteins, masking those originating from the cells lining the kidney tubules, which may better mirror disease progression. However, urine also contains nanosized vesicles (exosomes) released directly from kidney cells, which contain many low-abundance proteins that may be suitable progressive biomarkers. In this project, we will explore the use of urinary exosomes to diagnose and monitor CKD progression. Isolation and characterisation of extracellular vesicles with adherence to international guidelines, qualitative and quantitative proteomics using SWATH-MS, transcriptomics using digital technology and data mining using artificial neural network will lead to disease-stage specific bio profiles, which will improve our ability to stratify patients, predict progression and detect early response to therapy. Analysis of EV proteins associated with disease phenotypes will also offer an invaluable platform to gain insights into the disease pathobiology, by relying on cell and tissue tools and the supervisory team’s expertise in molecular cell biology.
We seek to recruit a science graduate or a medical graduate enthusiastic for this area and with some prior research experience. This is a joint project with industry, with access to world-class research capability, exposure to different approaches, and excellent networking opportunities for future employment.
Furini, G., Schroeder, N., Huang, L., Boocock, D., Scarpellini, A., Coveney, C., Tonoli, E., Ramaswamy, R., Ball, G., Verderio, C., Johnson, T.S., and Verderio, E.A.M. (2018) Proteomic Profiling Reveals the Transglutaminase-2 Externalization Pathway in Kidneys after Unilateral Ureteric Obstruction. J Am Soc Nephrol. 29:880-905.
Entrants must have an undergraduate Honours degree, with an Upper Second Class or a First Class grade in a Bioscience subject. Entrants with a Lower Second Class Honours degree must also have a postgraduate Masters Degree at Merit or Commendation.
How to apply
Contact Dr Elisabetta Verderio Edwards for informal discussions about this project.
Application deadline is 4th November at 11:59 pm.
Further information on how to apply can be found on this page.
Fees and funding
This is a fully-funded PhD opportunity for UK and EU candidates at level £4327.
Find out about fees and funding for PhD projects.
Guidance and support
Further information on guidance and support can be found on this page.