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Do urine vesicles offer a fingerprint of Chronic Kidney Disease

  • Full or part time
    Dr E Verderio-Edwards
  • Application Deadline
    Monday, November 04, 2019
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

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.

Funding Notes

Project jointly funded by Nottingham Trent University and an Industrial external partner (UCB Pharmaceuticals).

References

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

How good is research at Nottingham Trent University in General Engineering?

FTE Category A staff submitted: 14.40

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities

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