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Developing new approaches to study V-ATPase mechanism and inhibition

Project Description

Membrane proteins are the targets for over 60% of current therapeutics and are essential for cell survival and disease progression, however our current understanding of their structure and mechanism lags behind their soluble counterparts. Recent developments in the field of electron microscopy (EM) has made significant progress in this area and have been responsible for recently determining a number of important membrane protein structures. This project will build upon these developments, using novel approaches to studying membrane proteins and trapping different mechanical states. The primary focus of the project will be the vacuolar ATPase, an essential 1MDa protein complex which is responsible for numerous cellular pathways including receptor recycling, viral entry and cancer growth and homeostasis. This project has three primary aims; 1) To determine the structure of the V-ATPase bound to potent small molecule inhibitors, 2) Trap new conformational states and 3) to better understand the native membrane environment.
This PhD will be based in the Astbury Biostructure Laboratory, a world leading facility for EM and you will develop essential skills in structural biology, electron microscopy (single particle and tomography) along with membrane protein biochemistry. Moreover, this will introduce new methodologies such as time-resolved EM.

Funding Notes

White Rose BBSRC Doctoral Training Partnership in Mechanistic Biology
4 year fully-funded programme of integrated research and skills training, starting Oct 2020:
• Research Council Stipend
• UK/EU Tuition Fees
• Conference and research funding

At least a 2:1 honours degree or equivalent. We welcome students with backgrounds in biological, chemical or physical sciences, or mathematical backgrounds with an interest in biological questions.

EU candidates require 3 years of UK residency to receive full studentship

Not all projects will be funded; the DTP will appoint a limited number of candidates via a competitive process.

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How good is research at University of Leeds in Biological Sciences?

FTE Category A staff submitted: 60.90

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

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