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

用 PELDOR 和 CryoEM 阐明机械敏感 G 蛋白偶联受体的结构和功能

• 批准号: 2426653
• 金额: --
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2426653
• 关键词: Elucidating; Structure; Function; Mechanosensitive; protein

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.

膜蛋白 (MP) 构成基因组的重要组成部分，是约 30% 治疗的靶标，但我们对其结构和功能的了解往往落后于其可溶性部分，GPCR 占所有 MP 靶标的 50%，并且普遍表达。冷冻电子显微镜 (CryoEM) 和脉冲电子-电子双共振 (PELDOR，也称为 DEER) 光谱等技术的令人兴奋的新发展。改变了我们研究膜蛋白结构和功能的方式，并为我们的基本理解和推动治疗设计提供了新的见解。该项目将结合 PELDOR 光谱和 CryoEM，使用尖端技术并利用最新技术来探测膜蛋白结构/功能。对这些设施的投资约为 800 万英镑。工作重点是人类 G 蛋白偶联受体，它们是心血管病理生理学中的关键信号成分，我们的目标是为小分子药物开发提供新的见解。将接受过学术界和工业界感兴趣的互补尖端技术的培训。