Elucidating the Structure and Function of Mechanosensitive G-protein Coupled Receptors with PELDOR and CryoEM

Membrane proteins (MPs) make up a significant part of the genome and are the target of ~30% of therapeutics and yet our structural and functional understanding often lags behind their soluble counterparts. GPCRs account for 50% of all MP targets and are expressed ubiquitously in humans. Exciting new developments in techniques such as Cryo Electron Microscopy (CryoEM) and Pulsed Electron-Electron Double Resonance (PELDOR, also known as DEER) spectroscopy have changed the way we can study membrane protein structure and function and provide new insights into our fundamental understanding and drive therapeutic design. This project will combine PELDOR spectroscopy and CryoEM to probe membrane protein structure/function using cutting edge techniques and making use of the recent ~£8M investment in these facilities. Work will focus on human G-protein coupled receptors, which are critical signalling components in cardiovascular pathophysiology. By understanding their catalytic cycle we are aiming to provide new insights into small molecule drug development. The successful PhD student will be trained in complementary cutting edge techniques of interest to both academia and industry.