A World-Leading National Network for NMR in the Physical and Life Science: Very-High Field Infrastructure at Sheffield

世界领先的物理和生命科学核磁共振国家网络：谢菲尔德的超高现场基础设施

• 批准号: EP/S01358X/1
• 负责人: Michael Williamson
• 金额: $ 107.61万
• 依托单位: University of Sheffield
• 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=EP%2FS01358X%2F1
• 关键词: World; Leading; National; Network; NMR

We will deliver access to state-of-the-art very high field NMR capabilities to the UK NMR and wider research community across the physical and life sciences through the upgrading of the NMR Facility at the University of Sheffield. This will comprise an existing 800 MHz system that will be upgraded with a modern cryoprobe and console and focus on solution NMR applications, especially those requiring elevated pressure. The Sheffield NMR Facility will be run by existing staff to provide expertise in solution NMR to non-NMR specialist users, and will be one component of a UK hub and spoke network of NMR instrumentation to be run for the benefit of the whole UK research community. NMR spectroscopy is the most versatile of all the analytical tools; it provides insights into molecular structure, dynamics, and interactions. The higher sensitivity and resolution delivered with ultra- and very-high field NMR are transformative, providing information not accessible at lower field strength. The new capabilities of the Sheffield NMR Facility will support, extend and enhance research activities, both in the north and in the UK as a whole (see Academic Beneficiaries); enable and expand research in advanced chemical- and bio-materials, therapeutics, biotechnology and renewable energy; and catalyse new academic-industrial collaborations, focusing on and exploiting areas where there is excellence in the N8 and UK-wide. Examples include:(1) Structure determination of biological and chemical molecules and supra-molecular aggregates in solution;(2) Folding of linear polypeptides into complex biologically-active 3D structures, and the ways in which these processes can be altered or subverted in neurodegenerative diseases and cancer;(3) Catalytic processes, and the detailed analysis of the structure and dynamics of complex materials;(4) Metabolism within intact cells and organisms.UK research support targets that strengthen the UK's competitive position in key priority areas. By providing ready access to state-of-the-art instrumentation and expertise, the proposed Sheffield NMR Facility will enable UK research communities to continue to make major contributions across the range of research challenges aligned with national agendas and strategic priorities, and to respond rapidly and flexibly to initiatives such as the Industrial Strategy Challenge and the Global Challenges Research Funds.We will deliver on this major investment in NMR by: (1) Progressing a challenging scientific agenda based on national priorities such as advanced materials, renewable energy, industrial biotechnology and synthetic biology, and core health challenges;(2) Ensuring that the UK is at the forefront of NMR technique development in the solution state, by capitalising on our collective knowledge and experience, and providing training to the community through courses and summer schools; (3) Attracting industrial support, partnerships and engagement, founded upon a strong collective track record of using our scientific capabilities and assets to support economic growth; (4) Maximising the effective use of capital assets to ensure efficient provision of NMR access, building on our pioneering experience in equipment sharing, and operating and managing national facilities, within a long-term sustainability plan; (5) Aligning with the core individual and collective institutional strategies in the N8; (6) Developing annual reporting systems and symposia to disseminate findings and open new research strategies, and monitoring performance using defined Key Performance Indicators.

我们将通过谢菲尔德大学核磁共振设施的升级，为英国核磁共振和更广泛的物理和生命科学研究界提供最先进的高场核磁共振能力。这将包括现有的800 MHz系统，该系统将升级为现代冷冻探头和控制台，并专注于解决核磁共振应用，特别是那些需要高压的应用。谢菲尔德核磁共振设施将由现有员工运营，为非核磁共振专业用户提供核磁共振解决方案的专业知识，并将成为英国核磁共振仪器中心和辐条网络的一个组成部分，为整个英国研究界的利益而运行。核磁共振波谱是所有分析工具中最通用的；它提供了对分子结构、动力学和相互作用的见解。超高和超高场核磁共振带来的更高灵敏度和分辨率具有变革性，提供了在较低场强下无法获得的信息。谢菲尔德核磁共振设施的新能力将支持、扩展和加强北部和整个英国的研究活动（见学术受益人）；促进和扩大先进化学和生物材料、治疗方法、生物技术和可再生能源的研究；并促进新的学术-工业合作，重点关注和开发N8和全英国的卓越领域。例如：(1)溶液中生物和化学分子及超分子聚集体的结构测定；(2)线性多肽折叠成复杂的生物活性3D结构，以及这些过程在神经退行性疾病和癌症中被改变或颠覆的方式；(3)催化过程，复杂材料的结构和动力学的详细分析；(4)完整细胞和有机体内的代谢。英国研究支持的目标是加强英国在关键优先领域的竞争地位。通过提供最先进的仪器和专业知识，拟议中的谢菲尔德核磁共振设施将使英国研究界能够继续在与国家议程和战略重点一致的研究挑战范围内做出重大贡献，并迅速灵活地响应工业战略挑战和全球挑战研究基金等倡议。我们将通过以下方式实现对NMR的重大投资：(1)根据国家优先事项推进具有挑战性的科学议程，如先进材料、可再生能源、工业生物技术和合成生物学以及核心健康挑战；(2)通过利用我们的集体知识和经验，并通过课程和暑期学校向社区提供培训，确保英国在解决方案状态下处于核磁共振技术发展的前沿；(3)在利用我们的科学能力和资产支持经济增长的良好集体记录的基础上，吸引产业支持、伙伴关系和参与；(4)在长期可持续性计划中，最大限度地有效利用资本资产，以确保有效提供核磁共振访问，在设备共享和运营和管理国家设施方面建立我们的开创性经验；(5)与N8的核心个人和集体机构战略保持一致；(6)制定年度报告制度和专题讨论会，以传播研究成果和开辟新的研究战略，并使用确定的关键绩效指标监测绩效。

项目成果

Allomorphy as a mechanism of post-translational control of enzyme activity.

• DOI: 10.1038/s41467-020-19215-9
• 发表时间: 2020-11-02
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Wood HP;Cruz-Navarrete FA;Baxter NJ;Trevitt CR;Robertson AJ;Dix SR;Hounslow AM;Cliff MJ;Waltho JP
• 通讯作者: Waltho JP

The measurement of binding affinities by NMR chemical shift perturbation.

• DOI: 10.1007/s10858-022-00402-3
• 发表时间: 2022-08
• 期刊: JOURNAL OF BIOMOLECULAR NMR
• 影响因子: 2.7
• 作者: Hobbs, Billy;Drant, Jack;Williamson, Mike P.
• 通讯作者: Williamson, Mike P.

Decoration of the enterococcal polysaccharide antigen EPA is essential for virulence, cell surface charge and interaction with effectors of the innate immune system

• DOI: 10.1371/journal.ppat.1007730
• 发表时间: 2019-05-01
• 期刊: PLOS PATHOGENS
• 影响因子: 6.7
• 作者: Smith, Robert E.;Salamaga, Bartlomiej;Mesnage, Stephane
• 通讯作者: Mesnage, Stephane

The accuracy of protein structures in solution determined by AlphaFold and NMR

通过 AlphaFold 和 NMR 测定溶液中蛋白质结构的准确性

• DOI: 10.1101/2022.01.18.476751
• 发表时间: 2022
• 作者: Fowler N

Two-site recognition of Staphylococcus aureus peptidoglycan by lysostaphin SH3b

• DOI: 10.1038/s41589-019-0393-4
• 发表时间: 2020-01-01
• 期刊: NATURE CHEMICAL BIOLOGY
• 影响因子: 14.8
• 作者: Gonzalez-Delgado, Luz S.;Walters-Morgan, Hannah;Mesnage, Stephane
• 通讯作者: Mesnage, Stephane