Cryogen-Free Arbitrary Waveform EPR for Structural Biology and Biophysics

适用于结构生物学和生物物理学的无冷冻剂任意波形 EPR

基本信息

批准号：
BB/R013780/1
负责人：
Bela Bode
金额：
$ 26.63万
依托单位：
University of St Andrews
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2018
资助国家：
英国
起止时间：
2018 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FR013780%2F1
关键词：
Cryogen Free Arbitrary Waveform EPR

项目摘要

This equipment upgrade will enhance a large number of molecular biosciences related projects that utilise electron paramagnetic resonance (EPR) spectroscopy and will have a major impact in the biomedical sciences and structural biology at the Universities of St Andrews and Dundee and beyond.EPR is an ideal method for obtaining specific information at the nanoscale, as it is exquisitely sensitive to the magnetic spins of radicals and other paramagnetic centres. These are of interest as many are hotspots of biochemical activity. Recently, the number of applications utilising EPR has greatly increased. This increase was catalysed by new technology which allows researchers to selectively introduce spins into biomolecules and use them as molecular beacons. The magnetic moments of the spins interact with the magnetic moments of other paramagnets or magnetic nuclei and thus magnetically illuminate their surroundings. It has become increasingly popular to use measurements of the long-range distances between the spins to map the nanoworlds of protein conformations and interactions quite as if navigating by the relative positions and brightness of lighthouses.Recently, developments have started to transform this science. While spins are commonly manipulated by on/off electromagnetic irradiation, the advent of arbitrary waveform generators has opened up a whole new universe allowing access to new realms of information in experiments. This technology is often proposed to be the future of EPR and the analogous advancements have wholly transformed the field of nuclear magnetic resonance. Now that the more demanding technical requirements of EPR are fulfilled it seems a logical imperative to upgrade to this technology as the upgrade even just means a moderate additional cost compared to the initial investment.A second development concerns the need to cool the spins to extremely low temperatures using liquid helium. Helium is an expensive, finite resource that has proven to be highly susceptible to disruption in the supply chain and poses a considerable safety hazard. Traditionally, liquid helium would be connected to the spectrometer before performing EPR experiments. Recently, cryogen-free cryostats have been developed using closed-cycle cooling that operates like an ultra-low temperature refrigerator. In these cryostats, used helium is cooled by electrically driven compression and expansion cycles to re-liquefy and thus be recycled. This greatly improves reliability and sustainability. Significantly, this also reduces risks to the researchers whilst performing experiments. Additionally, the increased stability means that the facility can operate around the clock and for a longer period of time, allowing more experiments to be performed and more scientific questions to be answered in a given time, thereby substantially improving the efficiency of the facility.The Universities of St Andrews and Dundee have developed an extensive programme of biological applications using this methodology and now seek to implement cryogen-free arbitrary waveform EPR to enhance existing facilities for projects investigating biomedical challenges and opportunities in the bio-based economy of the future.

该设备升级将增强使用电子顺磁共振（EPR）光谱的大量分子生物科学项目，并将对St Andrews，Dundee和Dundee和Beyond的大学的生物医学科学和结构生物学产生重大影响。EPR是在Nancopique and exporiped and sporiped specoile specoile specorial specorial specipe and sporiped spociels spopiquic and sporiped spopiques and sefforips sporiped的理想方法中的重大影响。顺磁心中心。这些是感兴趣的，因为许多都是生化活动的热点。最近，利用EPR的应用程序数量已大大增加。这种增加是由新技术催化的，该技术使研究人员可以选择性地将旋转引入生物分子并将其用作分子信标。旋转的磁性力矩与其他Paramagnet或磁性核的磁矩相互作用，从而磁灯照亮其周围环境。使用旋转之间的远距离距离的测量值映射蛋白质构象和相互作用的纳米世界已经变得越来越流行，就好像通过灯塔的相对位置和亮度导航。虽然通常通过ON/OFF电磁辐射来操纵旋转，但任意波形发电机的出现已经打开了一个全新的宇宙，可以在实验中访问新的信息领域。通常认为这项技术是EPR的未来，类似的进步完全改变了核磁共振的领域。既然EPR的技术要求越来越大，升级到这项技术似乎是合乎逻辑的，因为升级甚至意味着与初始投资相比，第二个开发项目涉及使用液体氦气将旋转冷却到极低温度的必要性。氦气是一种昂贵的有限资源，已被证明非常容易在供应链中破坏，并带来了相当大的安全危险。传统上，液态氦在进行EPR实验之前将连接到光谱仪。最近，使用闭合循环冷却，像超低温度冰箱一样运行的闭合循环冷却。在这些低温器中，使用的氦气通过电动压缩和膨胀循环冷却，从而将其恢复并因此被回收。这大大提高了可靠性和可持续性。值得注意的是，这也降低了研究人员进行实验的风险。 Additionally, the increased stability means that the facility can operate around the clock and for a longer period of time, allowing more experiments to be performed and more scientific questions to be answered in a given time, thereby substantially improving the efficiency of the facility.The Universities of St Andrews and Dundee have developed an extensive programme of biological applications using this methodology and now seek to implement cryogen-free arbitrary waveform EPR to enhance existing facilities for projects investigating生物医学的挑战和未来生物经济的机会。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Investigating Native Metal Ion Binding Sites in Mammalian Histidine-Rich Glycoprotein

研究哺乳动物富含组氨酸的糖蛋白中的天然金属离子结合位点

DOI：
10.26434/chemrxiv-2023-f6n6p
发表时间：
2023
期刊：
影响因子：
0
作者：
Ackermann K
通讯作者：
Ackermann K

Investigating Native Metal Ion Binding Sites in Mammalian Histidine-Rich Glycoprotein.

DOI：
10.1021/jacs.3c00587
发表时间：
2023-04-12
期刊：
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
影响因子：
15
作者：
Ackermann, Katrin;Khazaipoul, Siavash;Wort, Joshua L.;Sobczak, Amelie I. S.;El Mkami, Hassane;Stewart, Alan J.;Bode, Bela E.
通讯作者：
Bode, Bela E.

Pulse dipolar EPR for determining nanomolar binding affinities.