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.

该提议是为了实现曼彻斯特大学的循环离子氢氘交换质谱法（环状IMS HDX-MS）。该竞标旨在提高对日益复杂和异质生物样品的高质量HDX-MS分析的能力和能力，这在很大程度上可以通过其他生物物理和生化方法进行棘手。它还将支持在细胞生物学，结构化学和分子医学之间的界面上的世界一流研究，对人类健康和疾病有直接影响。该仪器将使我们能够在高分辨率下衡量氢的氢交换，从而直接见解蛋白质如何与其他生物分子进行移动和相互作用。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周围环境的相互作用的研究，使用新兴的HDX-MS进行了与周围环境的相互作用。因此，PI在不仅在英国，而且在全球范围内的最佳地点都处于最佳状态。该仪器将通过在其生活和运作的本地环境中瞄准复杂且越来越大的生物系统来将研究提升到一个全新的水平。这将打开有关支持案例中概述多种疾病机制的方向。该HDX-MS仪器将安置在曼彻斯特生物技术研究所（MIB）和Michael Barber合作质谱中心。 MIB是科学与工程学院（FSE）和生物学，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行业的外部合作者都可以访问该工具。它本质上将构成曼彻斯特大学及其他地区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撑MRC的投资，并使与工业合作伙伴（例如Omass Therapeutics，Waters Corp.，Bioshape Ltd，Astrazeneca，Fujidiosynth）合作。新仪器将增强在其天然细胞环境中调查具有挑战性的生物系统的能力。它将提供无与伦比的灵敏度，获取速度和解决该技术中当前局限性的解决方案。这将使更广泛的研究获取和更广泛的应用在许多生物学过程中，例如膜运输，药物开发和设计，催化，大型分子机器以及相关疾病，例如癌症，结核病，心力衰竭，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地环境中进行研究的能力。

项目成果

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

• DOI: 10.26434/chemrxiv-2023-gzfhv
• 发表时间: 2023-12-20
• 期刊: chemRxiv
• 作者: Griffiths，Damon;Anderson，Malcolm;Politis，Argyris
• 通讯作者: Politis，Argyris