Faculty of Biology, Medicine and Health

The University of Manchester

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  Investigating renal dysfunction in a zebrafish model for Lowe syndrome

Prof Martin Lowe, Dr Adam Hurlstone  No more applications being accepted  Funded PhD Project (European/UK Students Only)

About the Project

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: http://www.ls.manchester.ac.uk/phdprogrammes

References



Where will I study?

Faculty of Biology, Medicine and Health

Tackle real world challenges, make a difference, and elevate your career with postgraduate research in the Faculty of Biology, Medicine and Health at Manchester. From biochemistry to neuroscience, cancer sciences to medicine, audiology to mental health and everything in between, we offer a wide range of postgraduate research projects, programmes and funding which will allow you to immerse yourself in an area of research you’re passionate about.

Why study at the Faculty of Biology, Medicine and Health?

Experience PhD life as part of a diverse postgraduate research community of more than 1,000 postgraduate researchers at the 29th most international university in the world (Times Higher Education, 2023).

Ranked the best place to live in the UK (The Economist Global Liveability Index, 2022), Manchester boasts world-class culture, iconic sports, a thriving music and food scene, and much more. It's not just a place to research, it's a place to call home.

With 93% of research activity at the University rated as 'world-leading' or 'internationally excellent' (Research Excellence Framework, 2021), you'll get the chance to have an impact on global health and science challenges.

1000+

postgraduate students

1

PhD

6th

in the UK - QS (2025)

Manchester  United Kingdom

main campus

About the Faculty of Biology, Medicine and Health

At Manchester, postgraduate researchers are at the heart of our mission to tackle pressing global challenges in biological, medical and healthcare sciences - and you could be too.

By choosing Manchester for your postgraduate research, you’ll be joining a university with an exceptional research reputation, where 93% of research is world-leading or internationally excellent (REF, 2021) and where your work will have real-world impact.

You’ll research in world-class facilities alongside leading experts at the forefront of innovation, collaborating across disciplines to pioneer new treatments, advance scientific knowledge, and improve healthcare globally.

Supported by our dedicated Doctoral Academy and strong industry links, you'll experience PhD life in a vibrant, welcoming and diverse postgraduate research community.

And you’ll leave with the specialist knowledge, research experience and transferable skills that will shape your future in academia, research or industry.





Main campus

The University of Manchester

Manchester

North West

United Kingdom