BioEmPiRe; Accessing uncharted but essential landscapes to biological machineries by pulse EPR

生物EmPiRe；

基本信息

批准号：
BB/W019795/2
负责人：
Christos Pliotas
金额：
$ 126.01万
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=BB%2FW019795%2F2
关键词：
BioEmPiRe Accessing uncharted but essential

项目摘要

To understand biological processes at a molecular detail one needs to capture and visualize proteins in action. Modern structural biology methods such as X-ray crystallography and cryo-electron microscopy (CryoEM) could provide static high-resolution snapshots of protein structures, but they are unable to capture proteins in motion to reveal dynamic function. The new state-of-the-art electron paramagnetic resonance (EPR) spectrometer in Leeds will be capable of extracting accurate distances between pairs of unpaired electrons engineered on protein sites and thus acting as a molecular nanoscale-ruler. The accurate measurement of such distances over a protein's functional cycle will thereby enable the elucidation of fundamental biological processes. Pulsed EPR is a powerful method in modern biomolecular research and has seen tremendous technical advances over the last 10 years with sensitivity increasing by more than an order of magnitude. As a network of protein structural molecular biologists in Leeds (including several leading EPR specialists), consider PELDOR as a key approach in the future of biosciences. We have a very large base of users in Leeds, nationally (Imperial, King's, Glasgow, St Andrews) and abroad (EU, Australia and India) and an unmatched variety of fundamental biological systems with representative proteins across all kingdoms of life. These proteins are involved in a wide range of disease-related biological mechanisms from cancer and neurodegeneration to antimicrobial resistance and metabolism. Novel information for fundamental biological machineries in molecular detail and currently inaccessible by other methods, would be first revealed by the new EPR spectrometer. Our investigators, collaborators and industrial partners come from a wide range of national and international institutions. We have an extensive track record in the field of EPR and biological and medical sciences and anticipate this installation will substantially increase the UK's capability and reputation in biological EPR worldwide. Our business case will ensure sustainability for the Leeds-based centre and will serve the North East and other Universities as demonstrated by our list of groups and investigators actively supporting BioEmPiRe. The position of an EPR staff scientist will be secured for an initial period of two years through a contribution by the University of Leeds. In addition, intended location will be fully refurbished and a chiller will be purchased to enable the optimal installation and operation of the spectrometer. The instrument will be part of the UK academic and industrial networks further ensuring sustainability. These upgrades will allow the UK to remain internationally competitive and to continue developing and applying the EPR methodology to important problems across the biosciences.

为了从分子细节上理解生物过程，我们需要捕获并可视化正在起作用的蛋白质。 X射线晶体学和冷冻电子显微镜（CryoEM）等现代结构生物学方法可以提供蛋白质结构的静态高分辨率快照，但它们无法捕获运动中的蛋白质以揭示动态功能。利兹最先进的新型电子顺磁共振（EPR）波谱仪将能够提取蛋白质位点上设计的不成对电子对之间的精确距离，从而充当分子纳米级标尺。准确测量蛋白质功能循环中的此类距离将有助于阐明基本的生物过程。脉冲 EPR 是现代生物分子研究中的一种强大方法，在过去 10 年中取得了巨大的技术进步，灵敏度提高了一个数量级以上。作为利兹的蛋白质结构分子生物学家网络（包括几位领先的 EPR 专家），将 PELDOR 视为未来生物科学的关键方法。我们在利兹、国内（帝国、国王、格拉斯哥、圣安德鲁斯）和国外（欧盟、澳大利亚和印度）拥有非常庞大的用户群，并且拥有无与伦比的各种基本生物系统，具有所有生命王国的代表性蛋白质。这些蛋白质参与广泛的疾病相关生物机制，从癌症和神经变性到抗菌素耐药性和代谢。新型 EPR 光谱仪将首先揭示分子细节方面的基本生物机制的新信息，这些信息目前无法通过其他方法获得。我们的研究人员、合作者和工业合作伙伴来自广泛的国家和国际机构。我们在 EPR 以及生物和医学科学领域拥有广泛的记录，预计此次安装将大大提高英国在全球生物 EPR 领域的能力和声誉。我们的业务案例将确保利兹中心的可持续性，并将为东北部和其他大学提供服务，正如我们积极支持 BioEmPiRe 的团体和研究人员名单所证明的那样。 EPR 科学家的职位将通过利兹大学的资助获得，最初为期两年。此外，预定地点将进行全面翻新，并购买一台冷却器，以实现光谱仪的最佳安装和操作。该仪器将成为英国学术和工业网络的一部分，进一步确保可持续性。这些升级将使英国保持国际竞争力，并继续开发和应用 EPR 方法来解决生物科学领域的重要问题。