Enabling new characterisation methods for dynamic systems through the upgrade of 700 MHz solution NMR spectrometer

通过升级 700 MHz 溶液核磁共振波谱仪，为动态系统提供新的表征方法

• 批准号: BB/W020297/1
• 负责人: Józef Lewandowski
• 金额: $ 101.86万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FW020297%2F1
• 关键词: Enabling; new; characterisation; methods; dynamic

The high field 700 MHz solution NMR spectrometer at the University of Warwick was installed during 2004-2005. Since then it has supported large number of research projects mainly funded by the BBSRC and other UKRI councils, led to numerous high-impact interdisciplinary publications in journals such as Nature, Nature Chemistry and Nature Chemical Biology. It has also played a pivotal role in training up the next generation of NMR specialists, many of our research students/PDRAs have benefited enormously from accessing to this instrument. The instrument is central to biomolecular solution NMR research activities, across departments within the University of Warwick via multidisciplinary collaborative networks, as well as supporting high-profile collaborations outside Warwick. However, after more than a decade of heavily usage, it is now >5 years beyond its end-of-life cycle, the Avance II console and the old TCI cryoprobe are completely obsolete, resulting in frequent malfunctions, extended downtime and limited capabilities. More importantly, since the spectrometer's installation, huge advances have been made both in the console design and cryoprobe technology, which enable a wide range of new powerful techniques and are not possible with the old-generation of instrumentation.In this proposal, we request funds to renew the 700 MHz solution NMR system by upgrading the aging console to Avance NEO and purchasing new cryoprobes, TXO and TCI, which will expand our NMR capacity and enable cutting-edge capabilities in biological NMR spectroscopy, to support large number of both established and early-career research staff (>20 PIs and their research groups) involved in a wide range of internationally leading research. The proposed upgrade is of utmost urgency to avoid negatively impacting on a well established and very successful field of research at Warwick. The new TCI probe will deliver substantial improvements in sensitivity for samples dissolved in high ionic strength physiological solutions and supporting work from small molecule, bioactive natural products discovery to proteins. It will also provide new capabilities for fluorine spectroscopy and related state-of-the-art experiments for characterising interactions, conformational dynamics and structures of biomolecular systems (e.g. protein-glycan systems and large protein complexes). The addition of a TXO probe will additionally bring new cutting-edge capabilities for advanced large and dynamic protein-based work, which will fortify our internationally leading position in field such as genome guided bioactive natural product discovery and integrated structural biology of biosynthetic enzymes. Both local and national NMR communities in the UK can also benefit from this upgrade, we have co-ordinated our application with colleagues in the Midland to ensure that newly gained capabilities are complementary with existing facilities in the region. We also proposed to offer up to 15% of the instrument time to the UK NMR communities through a transparent peer-review process and access mechanism integrated with the UKRI funded ConnectNMR network.

华威大学的高场700 MHz溶液核磁共振光谱仪于2004-2005年期间安装。从那时起，它支持了大量主要由BBSRC和其他UKRI理事会资助的研究项目，并在《自然》、《自然化学》和《自然化学生物学》等期刊上发表了许多高影响力的跨学科出版物。它在培养下一代核磁共振专家方面也发挥了关键作用，我们的许多研究生/ pdra都从使用该仪器中受益匪浅。该仪器是生物分子溶液核磁共振研究活动的核心，通过多学科合作网络跨华威大学的部门，以及支持华威大学以外的高调合作。然而，经过十多年的大量使用，Avance II控制台和旧的TCI冷冻探针已经完全过时，导致故障频繁，停机时间延长，功能有限。更重要的是，自光谱仪安装以来，在控制台设计和冷冻探针技术方面都取得了巨大的进步，这使得各种新的强大技术成为可能，而这些技术是老一代仪器无法实现的。在本提案中，我们要求资金更新700 MHz解决方案核磁共振系统，将老化的控制台升级到Avance NEO，并购买新的冷冻探头，TXO和TCI，这将扩大我们的核磁共振能力，并使生物核磁共振光谱的尖端能力成为可能，以支持大量成熟和早期职业研究人员（bbb20 pi及其研究小组）参与广泛的国际领先研究。拟议的升级是最紧迫的，以避免对华威大学建立良好且非常成功的研究领域产生负面影响。新的TCI探针将大大提高溶解在高离子强度生理溶液中的样品的灵敏度，并支持从小分子、生物活性天然产物发现到蛋白质的工作。它还将为氟光谱和相关的最先进的实验提供新的能力，用于表征生物分子系统（例如蛋白质-聚糖系统和大蛋白质复合物）的相互作用、构象动力学和结构。TXO探针的加入将为先进的大型动态蛋白质研究带来新的前沿能力，这将巩固我们在基因组引导的生物活性天然产物发现和生物合成酶综合结构生物学等领域的国际领先地位。英国的地方和国家核磁共振社区也可以从这次升级中受益，我们已经与米德兰的同事协调了我们的应用程序，以确保新获得的能力与该地区现有的设施相辅相成。我们还建议通过透明的同行评审过程和与UKRI资助的ConnectNMR网络集成的访问机制，为英国NMR社区提供高达15%的仪器时间。