High resolution cyclic ion mobility HDX mass spectrometry of protein dynamics and function

蛋白质动力学和功能的高分辨率循环离子淌度 HDX 质谱分析

• 批准号: MR/X013030/1
• 负责人: Argyris Politis
• 金额: $ 75.28万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX013030%2F1
• 关键词: resolution; cyclic; ion; mobility; HDX

This proposal is to enable cyclic ion mobility hydrogen deuterium exchange mass spectrometry (cyclic IMS HDX-MS) at the University of Manchester. The bid aims to increase capacity and capability for high-quality HDX-MS analysis of increasingly complex and heterogeneous biological samples, largely intractable by other biophysical and biochemical methods. It will also support world-class research at the interface between cellular biology, structural chemistry and molecular medicine with direct implications into human health and disease. The instrumentation will allow us to measure the exchange of hydrogen for heavier deuterium at high resolution enabling direct insights into how proteins move and interact with other biomolecules.Over the past few years, the PI has pioneered the study of challenging membrane proteins and their interactions with their surrounding environment using emerging HDX-MS. As such the PI is at the best place o lead this bid not only in the UK but also worldwide. The instrumentation will allow taking the research to an entirely new level by targeting complex and increasingly larger biological systems in the native environment where they live and function. This will open up directions in understanding the mechanism of a multitude of diseases outlined in the case for support.This HDX-MS instrument will be housed at the Manchester Institute for Biotechnology (MIB) and in the Michael Barber Centre for Collaborative Mass Spectrometry. MIB is the home of research groups from both the faculty of science and engineering (FSE) and the faculty of biology, medicine and health (FBMH). The instrument will be accessible by research groups from both FSE and FBMH and by external collaborators from both academia and industry. It will essentially form a basis for an interdisciplinary network of collaborations within the University of Manchester and beyond. We will use this state-of-the-art equipment to underpin investments by MRC and enable working with industrial partners (e.g. OMass Therapeutics, Waters Corp., BioShape Ltd, AstraZeneca, FujiDiosynth). The new instrument will enhance capacity and capability for investigating challenging biological systems within their native cellular environment. It will offer unsurpassed sensitivity, speed of acquisition and resolution circumventing current limitations in the technique. This will enable broader research access and wider application to many biological processes such as membrane transport, drug development and design, catalysis, and large molecular machines and related diseases such as cancer, tuberculosis, heart failure and antimicrobial resistance. This will further offer the ability to carry out research in human samples and in their native environments.

这项提议是为了使曼彻斯特大学的环离子迁移率氢-重离子交换质谱仪(Cycle IMS HDX-MS)成为可能。此次招标旨在提高对日益复杂和不同种类的生物样品进行高质量HDX-MS分析的能力和能力，这些样品在很大程度上是其他生物物理和生化方法难以解决的。它还将支持在细胞生物学、结构化学和分子医学之间的世界级研究，对人类健康和疾病有直接影响。该仪器将使我们能够以高分辨率测量氢与较重的重氢的交换，从而能够直接了解蛋白质如何移动并与其他生物分子相互作用。在过去的几年里，PI开创了利用新兴的HDX-MS研究具有挑战性的膜蛋白质及其与周围环境相互作用的先河。因此，PI不仅在英国，而且在世界范围内都处于领导这一竞标的最佳位置。该仪器将使研究达到一个全新的水平，通过瞄准它们生活和功能所在的自然环境中的复杂和越来越大的生物系统。这将为理解支持案例中概述的多种疾病的机制开辟方向。这台HDX-MS仪器将安装在曼彻斯特生物技术研究所(MIB)和迈克尔·巴伯合作质谱学中心。MIB是来自科学与工程学院(FSE)和生物、医学与健康学院(FBMH)的研究小组的所在地。FSE和FBMH的研究小组以及学术界和工业界的外部合作者都可以使用该仪器。它将基本上形成曼彻斯特大学内外跨学科合作网络的基础。我们将使用这种最先进的设备来支持MRC的投资，并支持与工业合作伙伴(例如OMassa治疗公司、Waters Corp.、BioShape Ltd、阿斯利康、FujiDiSynth)的合作。新仪器将增强在其自然细胞环境中调查具有挑战性的生物系统的能力和能力。它将提供无与伦比的灵敏度、采集速度和分辨率，绕过了目前该技术的限制。这将使更广泛的研究途径和更广泛的应用于许多生物过程，如膜转运、药物开发和设计、催化、大分子机器和相关疾病，如癌症、结核病、心力衰竭和抗菌素耐药性。这将进一步提供在人类样本及其本土环境中进行研究的能力。