FlexX

柔性X

• 批准号: 10231136
• 负责人: Aaron D Finke
• 金额: $ 74.29万
• 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/10231136
• 关键词: Biological; Biological Process; Biology; Biomedical Research; Carbon Dioxide; Categories; Communities; Complement; Complex; Computer software; Confocal Microscopy; Crystallization; Crystallography; Data; Data Collection; Data Set; Development; Diffuse; Disease; Education and Outreach; Emerging Technologies; Environment; Enzymes; Equipment; Funding; Gene Expression; Goals; Government; Growth Factor Receptors; Humidity; Image; Institution; Ion Channel; Knowledge; Lighting; Macromolecular Complexes; Measurement; Membrane; Methodology; Methods; Minor; Modification; Molecular; Molecular Conformation; Motion; Neurons; Nucleic Acids; Oxygen; Preparation; Proteins; RNA Splicing; Radiation; Receptor Signaling; Regulation; Research Personnel; Resolution; Roentgen Rays; Sampling; Services; Shapes; Signaling Protein; Site; Source; Structural Biologist; Structure; Support Groups; Synchrotrons; System; Techniques; Technology; Temperature; Time; Training; United States National Institutes of Health; Work; beamline; clinical development; design; detector; enzyme mechanism; experimental study; flexibility; frontier; improved; insight; interest; macromolecular assembly; method development; new therapeutic target; novel; operation; pressure; protein complex; receptor; structural biology; working group

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.

项目概要： MacCHESS 结构生物学同步加速器源促进了两者的利用 现有技术和新兴技术来推进生物医学研究目标。工作执行于 MacCHESS 预计将对生物学和生物医学产生根本性的重要见解，增加 对复杂膜受体信号系统的理解，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装体 负责基因表达。 CHESS 的升级，包括存储环和 新设计的光束线将于 2019 年 6 月到位，提供最先进的设施。 MacCHESS 将继续支持由 NIH 和其他机构资助的 100 多个研究项目 政府机构，通过两个主要的技术运营核心。这些是： 1) 设施 灵活的晶体学。灵活的晶体学技术核心将利用独特的优势 MacCHESS 功能支持开发新的 X 射线技术，可用于拓宽 生物过程的知识。例子包括持续开发串行方法 晶体学、晶体处理技术的改进、晶体高压的应用、 通过研究 X 射线漫散射来分析大分子运动。高水平 还将提供对更常规的大分子晶体学的支持，以回答一系列问题 涉及单一蛋白质、核酸和大分子复合物的结构问题，以及 为从不太标准的类型获得的结果提供有价值的补充信息 结构研究。 2) 生物小角X射线散射设施(BioSAXS)。这项技术 核心将采用最先进的硬件、软件和专业知识来支持日益先进的 需要BioSAXS技术。除了确定蛋白质、核酸和更大分子的形状外 BioSAXS 允许研究人员获取有关全局构象的信息 大分子复合物（例如生长因子受体、RNA剪接复合物）内的变化和/或 其寡聚状态的变化具有重要的功能后果。该核心还将 为有兴趣执行时间分辨的研究人员提供必要的设备和专业知识 BioSAXS 或 BioSAXS 研究在高压下进行。 MacCHESS 将提供强大的 管理核心支持这些活动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 为我们的用户提供解决结构生物学中一些最具挑战性问题的机会 获得结构功能信息，最终突出新的治疗靶点并有助于 制定应对疾病的临床策略。