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.

该提案旨在让曼彻斯特大学实现循环离子淌度氢氘交换质谱（循环 IMS HDX-MS）。该投标旨在提高对日益复杂和异质的生物样本进行高质量 HDX-MS 分析的能力和能力，而其他生物物理和生化方法在很大程度上难以处理这些样本。它还将支持细胞生物学、结构化学和分子医学之间的世界级研究，对人类健康和疾病产生直接影响。该仪器将使我们能够以高分辨率测量氢与重氘的交换，从而能够直接了解蛋白质如何移动以及与其他生物分子相互作用。在过去的几年中，PI 率先研究了具有挑战性的膜蛋白及其与其他生物分子的相互作用。他们的周围环境使用新兴的 HDX-MS。因此，PI 不仅在英国而且在全球范围内都处于领导本次投标的最佳位置。该仪器将通过针对复杂且日益庞大的生物系统生活和发挥作用的原生环境中的目标，将研究提升到一个全新的水平。这将为理解支持案例中概述的多种疾病的机制开辟方向。该 HDX-MS 仪器将安置在曼彻斯特生物技术研究所 (MIB) 和迈克尔·巴伯协作质谱中心。 MIB 是科学与工程学院 (FSE) 和生物、医学与健康学院 (FBMH) 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工具。它将本质上构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，并促进与工业合作伙伴（例如 OMass Therapeutics、Waters Corp.、BioShape Ltd、AstraZeneca、FujiDiosynth）的合作。新仪器将增强在其天然细胞环境中研究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，突破当前技术的限制。这将使更广泛的研究进入和更广泛地应用到许多生物过程，如膜运输、药物开发和设计、催化、大分子机器以及癌症、结核、心力衰竭和抗菌素耐药性等相关疾病。这将进一步提供在人类样本及其原生环境中进行研究的能力。

项目成果

Cyclic ion mobility for hydrogen/deuterium exchange-mass spectrometry applications

用于氢/氘交换质谱应用的循环离子淌度

• DOI: http://dx.10.26434/chemrxiv-2023-gzfhv
• 发表时间: 2023
• 作者: Griffiths D