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.

沃里克大学的高场700 MHz解决方案NMR光谱仪是在2004 - 2005年期间安装的。从那时起，它支持了大量主要由BBSRC和其他乌克里委员会资助的研究项目，导致在自然，自然化学和自然化学生物学等期刊上提供了许多高影响力的跨学科出版物。它在培训下一代NMR专家方面也发挥了关键作用，我们的许多研究专业的学生/PDRA都从访问该乐器中受益匪浅。该工具是沃里克大学通过多学科协作网络跨越沃里克大学的部门的生物分子解决方案的核心，并支持沃里克以外的备受瞩目的合作。但是，经过十多年的大量使用，现在已经超出了寿命末期> 5年，Avance II控制台和旧的TCI冷冻螺旋桨完全过时，导致频繁出现故障，延长停机时间和有限的功能。 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我们的NMR能力和能够在生物NMR光谱中的最先进能力，以支持大量建立和早期研究人员（> 20个PIS及其研究小组），参与了广泛的国际领先研究。拟议的升级是避免对沃里克良好且非常成功的研究领域产生负面影响的最紧迫性。新的TCI探测器将对溶解在高离子强度生理溶液中的样品的敏感性方面进行实质性改善，并从小分子，生物活性天然产物发现到蛋白质的支持。它还将为氟光谱和相关的最新实验提供新的功能，以表征相互作用，构象动力学和生物分子系统的结构（例如蛋白质 - 聚糖系统和大型蛋白质复合物）。 TXO探针的添加还将为高级大型和动态蛋白质的工作带来新的尖端功能，这将增强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的整合结构生物学等领域的国际领先地位。英国的本地和国家NMR社区也可以从此升级中受益，我们已经与中部地区的同事协调了我们的申请，以确保新获得的能力与该地区现有设施互补。我们还建议通过与UKRI资助的ConnectNMR网络集成的透明同行评审过程和访问机制，向英国NMR社区提供多达15％的仪器时间。