PhD Research Project

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Investigating renal dysfunction in a zebrafish model for Lowe syndrome

Institution:

University of Manchester

Dept/School/Faculty:

Faculty of Life Sciences

PhD Supervisor:

Prof M Lowe

Co-Supervisor:

Dr A Hurlstone

Application Deadline:

No more applications being accepted

Funding Availability:

Funded PhD Project (European/UK Students Only)

PhD Research Project

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Lowe syndrome (LS), a disorder that mainly affects the brain, kidneys and eyes, is caused by mutation of a single gene, called OCRL1. Interestingly, mutation of OCRL1 also causes Dent-2 disease, which can be thought of as a milder form of LS in which kidney defects are most obvious. Renal impairment ultimately leading to renal failure is a major cause of morbidity in both LS and Dent-2. It is therefore important we understand how loss of OCRL1 leads to defects in the kidneys, but, unfortunately, we have a poor appreciation of the mechanisms involved. To better understand how the renal pathology of LS and Dent-2 is brought about, we have generated a transgenic zebrafish lacking OCRL1. We have shown that this zebrafish model recapitulates neurological features of LS, and more recently that it exhibits impaired renal function. Preliminary studies suggest that defects in endocytic trafficking are responsible for the observed defects. This PhD project aims to build upon this exciting finding to dissect the underlying mechanisms. Using a number of complimentary approaches we will investigate how loss of OCRL1 affects endocytic trafficking, and how defective endocytosis leads to the renal manifestations of LS and Dent-2. Information gained from the mechanistic studies will be used to generate a reporter zebrafish strain for high-throughput screening for drugs to treat both LS and Dent-2.

Funding Notes:

This studentship is available to UK and other EU nationals (due to funding criteria) and provides fees and stipend subject to eligibility. Applicants should hold (or be about to obtain) a first or upper seond class honours degree in a related area.

To apply for this studentship please see: www.ls.manchester.ac.uk/phdprogrammes