MacCHESS Synchrotron Source for Structural Biology

MacCHESS 结构生物学同步加速器源

• 批准号: 10443671
• 负责人: RICHARD A. CERIONE
• 金额: $ 279.41万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10443671
• 关键词: Address; Biological; Biological Process; Biological Products; Biology; Biomedical Research; Characteristics; Collection; Communities; Complex; Computer software; Country; Crystallization; Crystallography; Data; Data Collection; Development; Diffuse; Disease; Education and Outreach; Educational workshop; Emerging Technologies; Equipment; Funding; Future; Gene Expression; Generations; Goals; Government; Growth Factor Receptors; Human Resources; Institution; Ion Channel; Knowledge; Leadership; Macromolecular Complexes; Membrane; Methodology; Methods; Mission; Molecular; Molecular Conformation; Motion; Neurons; Nucleic Acids; Postdoctoral Fellow; Procedures; Process; Proteins; Publishing; RNA Splicing; Receptor Signaling; Regulation; Reporting; Research Personnel; Resolution; Resources; Roentgen Rays; Role; Running; Schedule; Science; Scientist; Seasons; Services; Shapes; Signaling Protein; Source; Special Equipment; Strategic Planning; Structural Biologist; Structure; Students; Synchrotrons; System; Techniques; Technology; Time; Training; United States National Institutes of Health; Visit; Work; base; beamline; clinical development; design; enzyme mechanism; experience; experimental study; flexibility; frontier; improved; insight; instrumentation; interest; macromolecular assembly; macromolecule; method development; new technology; new therapeutic target; novel; operation; pressure; programs; protein complex; receptor; structural biology; success; Address; Biological; Biological Process; Biological Products; Biology; Biomedical Research; Characteristics; Collection; Communities; Complex; Computer software; Country; Crystallization; Crystallography; Data; Data Collection; Development; Diffuse; Disease; Education and Outreach; Educational workshop; Emerging Technologies; Equipment; Funding; Future; Gene Expression; Generations; Goals; Government; Growth Factor Receptors; Human Resources; Institution; Ion Channel; Knowledge; Leadership; Macromolecular Complexes; Membrane; Methodology; Methods; Mission; Molecular; Molecular Conformation; Motion; Neurons; Nucleic Acids; Postdoctoral Fellow; Procedures; Process; Proteins; Publishing; RNA Splicing; Receptor Signaling; Regulation; Reporting; Research Personnel; Resolution; Resources; Roentgen Rays; Role; Running; Schedule; Science; Scientist; Seasons; Services; Shapes; Signaling Protein; Source; Special Equipment; Strategic Planning; Structural Biologist; Structure; Students; Synchrotrons; System; Techniques; Technology; Time; Training; United States National Institutes of Health; Visit; Work; base; beamline; clinical development; design; enzyme mechanism; experience; experimental study; flexibility; frontier; improved; insight; instrumentation; interest; macromolecular assembly; macromolecule; method development; new technology; new therapeutic target; novel; operation; pressure; programs; protein complex; receptor; structural biology; success

Project summary: The MacCHESS Synchrotron Source for Structural Biology facilitates the utilization of both established and emerging technologies to advance biomedical research goals. Work performed at MacCHESS is expected to yield fundamentally important insights into biology and biomedicine, adding to the understanding of complex membrane receptor-signaling systems, the regulation of ion channels in neuronal function, catalytic mechanisms of enzymes, and the complex macromolecular assemblies responsible for gene expression. Upgrades to CHESS, including improvements to the storage ring and newly designed beamlines that will provide state-of-the-art facilities, will be in place by June 2019. MacCHESS will continue to support more than 100 investigator projects, funded by NIH and other government institutions, through two major Technology Operations Cores. These are: 1) Facility for Flexible Crystallography. The Flexible Crystallography Technology Core will take advantage of unique MacCHESS capabilities to enable the development of new X-ray techniques that may be used to broaden knowledge of biological processes. Examples include continued development of methods for serial crystallography, improvements in crystal handling techniques, the application of high pressure to crystals, and analysis of macromolecular motions through the study of X-ray diffuse scattering. A high level of support for more routine macromolecular crystallography will also be provided, to answer a range of structural questions involving single proteins, nucleic acids, and macromolecular complexes, as well as to provide valuable complementary information to the results obtained from the less standard types of structural studies. 2) Facility for Biological Small Angle X-ray Scattering (BioSAXS). This technology core will implement state-of-the-art hardware, software, and expertise to support the increasingly in- demand BioSAXS technique. In addition to determining the shapes of proteins, nucleic acids, and larger assemblies in solution, BioSAXS allows researchers to obtain information regarding global conformational changes within macromolecular complexes (e.g. growth factor receptors, RNA-splicing complexes) and/or the changes in their oligomeric states that have important functional consequences. This core will also provide the necessary equipment and expertise for investigators interested in performing time-resolved BioSAXS or BioSAXS studies conducted under high pressure. MacCHESS will provide a strong Administration Core to support these activities and will continue to educate users, and the biomedical research community, through a Training and Outreach Core. Collectively, these efforts will offer unique opportunities to our users for pursuing some of the most challenging questions in structural biology and for obtaining structure-function information that will ultimately highlight novel therapeutic targets and aid in the development of clinical strategies for dealing with disease.

项目摘要： 结构生物学的MacChess同步源促进了两者的利用 建立和新兴技术以促进生物医学研究目标。执行的工作 预计MacChess将对生物学和生物医学产生根本上重要的见解，从而增加 对复杂的膜受体信号系统的理解，对离子通道的调节 神经元功能，酶的催化机制和复杂的大分子组件 负责基因表达。升级到国际象棋，包括对存储环的改进和 新设计的光束线将在2019年6月之前提供最先进的设施。 MacChess将继续支持由NIH和其他资助的100多个调查员项目 政府机构通过两个主要的技术运营核心。这些是：1） 柔性晶体学。灵活的晶体学技术核心将利用独特的优势 MacChess的功能，可以开发新的X射线技术来扩展 了解生物过程。例子包括持续开发串行方法 晶体学，晶体处理技术的改进，高压在晶体中的应用， 通过研究X射线扩散散射对大分子运动的分析。高水平 还将提供对更多常规大分子晶体学的支持，以回答一系列 结构性问题涉及单蛋白，核酸和大分子复合物，以及 为从不标准类型的结果获得有价值的互补信息 结构研究。 2）生物小角度X射线散射的设施（Biosaxs）。这项技术 核心将实施最先进的硬件，软件和专业知识，以支持越来越多的内在 需求Biosaxs技术。除了确定蛋白质，核酸和较大的形状外 解决方案中的组装，BioSaxs允许研究人员获取有关全球构象的信息 大分子复合物（例如生长因子受体，RNA切成络合物）和/或 具有重要功能后果的低聚状态的变化。这个核心也将 为有兴趣执行时间分辨的调查人员提供必要的设备和专业知识 在高压下进行的生物族或生物族研究。 MacChess将提供强大的 管理这些活动的核心，并将继续教育用户和生物医学 研究社区，通过培训和外展核心。总的来说，这些努力将提供独特的 我们的用户的机会是在结构生物学和 获取结构功能信息，最终将突出显示新的治疗靶标并有助于 制定处理疾病的临床策略。