800 MHz NMR SPECTROMETER

800 MHz 核磁共振波谱仪

• 批准号: 6501642
• 负责人: Jose Rizorey
• 金额: $ 200万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6501642
• 关键词: biomedical equipment purchase; nuclear magnetic resonance spectroscopy

DESCRIPTION (provided by applicant): The University of Texas Southwestern Medical Center in Dallas has initiated a major expansion in its NMR faculty and facilities. To drive this program, the University has committed over $5M for purchase of additional instruments, construction of state-of-the-art facilities, hiring of dedicated support personnel and appointment of senior faculty. Integral to this program is the purchase of an 800 MHz spectrometer equipped with a cryoprobe to support new research initiatives that cannot be carried out on lower field instruments, and funds are requested to assist in this endeavor. This instrument will support the research of 30 users in the four principal NMR groups in the Departments of Biochemistry and Pharmacology, plus numerous collaborators and minor users within and outside the university. Research using the instrument will address central questions in a broad range of biological areas, including molecular mechanisms of neurotransmitter release and constitutive intracellular membrane traffic, control of actin cytoskeletal architecture and dynamics through integrated signaling networks, regulation of cellular hypoxia responses and circadian cycling, and molecular mechanisms of a mitotic checkpoint that ensures the high-fidelity segregation of chromosomes in mitosis. Specific structural/biophysical problems in these areas include studies of the calcium sensor, synaptotagmin, and its interaction with SNARE proteins, essential components of the membrane fusion machinery; the activation mechanism of the 240 kDa Arp2/3 complex, the central actin nucleating machine in the cell, the biophysical foundations of signal integration by autoinhibitory proteins; the ability of PAS domains to control biological function through changes in protein structure and dynamics induced by natural and non-natural ligands; competition for the mitotic checkpoint protein Mad2 by its upstream regulator, Mad1, and its downstream target, Cdc20. These studies will require NMR analyses of multi-component systems ranging in size from 15-250 kDa, and will involve innovative use of CRIPT/TROSY methods, lanthanide-assisted magnetic field alignment, multi-field dynamics studies and analysis of very dilute solutions, necessitating maximum field strength and sensitivity. In summary, an 800 MHz spectrometer at UT Southwestern will foster cutting edge science in important biological areas that will expand the boundaries of NMR methods to large and/or complex systems. The instrument will be strongly supported by the University, and administered through a detailed plan that ensures efficient use and maintenance, specific mechanisms for training new users and dissemination of results to the larger communitv.

描述（由申请人提供）：位于达拉斯的德克萨斯大学西南医学中心已开始对其 NMR 师资和设施进行重大扩建。为了推动这一计划，大学已承诺投入超过 500 万美元用于购买额外仪器、建造最先进的设施、雇用专门的支持人员以及任命高级教师。该计划的一个组成部分是购买一台配备冷冻探针的 800 MHz 光谱仪，以支持无法在较低的现场仪器上进行的新研究计划，并且需要资金来协助这项工作。该仪器将支持生物化学和药理学系四个主要 NMR 小组的 30 位用户以及大学内外的众多合作者和小型用户的研究。使用该仪器的研究将解决广泛的生物学领域的核心问题，包括神经递质释放和组成性细胞内膜运输的分子机制、通​​过集成信号网络控制肌动蛋白细胞骨架结构和动力学、细胞缺氧反应和昼夜节律循环的调节，以及确保高保真分离的有丝分裂检查点的分子机制。 有丝分裂中的染色体。这些领域的具体结构/生物物理问题包括对钙传感器、突触结合蛋白及其与 SNARE 蛋白（膜融合机制的重要组成部分）相互作用的研究； 240 kDa Arp2/3 复合物的激活机制，细胞中的中央肌动蛋白成核机，自抑制蛋白信号整合的生物物理基础； PAS 结构域通过天然和非天然配体诱导的蛋白质结构和动力学变化来控制生物功能的能力；有丝分裂检查点蛋白 Mad2 的上游调节因子 Mad1 及其下游靶标 Cdc20 竞争。这些研究需要对尺寸范围为 15-250 kDa 的多组分系统进行 NMR 分析，并将涉及 CRIPT/TROSY 方法的创新使用、镧系元素辅助磁场对准、多场动力学研究和非常稀溶液的分析，需要最大的场强和灵敏度。总之，UT 西南大学的 800 MHz 光谱仪将促进重要生物领域的尖端科学，将 NMR 方法的边界扩展到大型和/或复杂系统。该工具将得到大学的大力支持，并通过详细的计划进行管理，以确保有效使用和维护、培训新用户的具体机制以及向更大的社区传播结果。