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(MRC DTP) Understanding mechanisms of endocytosis in the renal tubule and how it goes wrong in kidney disease


Project Description

The renal tubule is responsible for a number of important physiological processes amongst which includes the reabsorption of low molecular weight proteins from the renal filtrate. Uptake of low molecular weight proteins into renal tubular cells is mediated by endocytosis, but the molecular mechanisms underlying this process remain poorly defined. Defective uptake of proteins in the renal tubule is associated with a number of kidney disorders in humans, including Donnai-Barrow syndrome, Lowe syndrome and Dent disease. It is therefore important we understand the molecular mechanisms involved, and how the process is dysregulated in disease. The goal of this project is to understand how endocytic traffic is mediated within the renal tubule, focussing on the actin- and membrane-associated protein Pacsin 2, together with its interaction partners. Our preliminary studies in both cell culture and zebrafish models, point to a role for these proteins in maintaining endocytic function within the kidney, which is further supported by the analysis of human patients harbouring mutations in the relevant genes. Currently, however, we do not understand the mechanisms by which these proteins function in endocytosis, or how mutations in their genes lead to endocytic dysfunction and disease. This gap in knowledge will be addressed using a combination of in vitro cell biology using renal cell models, combined with experiments in zebrafish larvae, which are an excellent model for investigating renal endocytosis in an in vivo context. A combination of molecular and imaging approaches will be used in these experiments, which together will provide new insight into how the kidney functions normally and how it goes awry in human disease.

http://www.manchester.ac.uk/research/martin.p.lowe/
https://www.manchester.ac.uk/research/philip.woodman/
http://www.manchester.ac.uk/research/rachel.lennon/

Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

Funding Notes

This project is to be funded under the MRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the MRC DTP website View Website

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

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