MacCHESS Synchrotron Source for Structural Biology

项目总结： 用于结构生物学的MacCHESS同步加速器源促进了两者的利用 促进生物医学研究目标的成熟技术和新兴技术。在以下时间执行的工作 预计MacCHESS将在生物学和生物医学方面产生根本性的重要见解，进一步 了解复杂的膜受体-信号系统，离子通道的调节 神经功能、酶的催化机制和复杂的大分子组件 负责基因表达。升级国际象棋，包括改进储物环和 新设计的光束线将提供最先进的设施，将于2019年6月到位。 MacCHESS将继续支持100多个由NIH和其他机构资助的调查项目 政府机构，通过两个主要的技术运营核心。这些是：1)设施 柔性结晶学。灵活的晶体技术核心将利用独特的 MacCHESS的能力，使新的X射线技术的开发可以用于扩大 关于生物过程的知识。例子包括继续开发连续的方法 结晶学，晶体处理技术的改进，对晶体的高压应用， 并通过X射线漫散射的研究分析了大分子的运动。高水平的 还将提供对更常规的大分子结晶学的支持，以回答一系列 涉及单一蛋白质、核酸和大分子复合体的结构问题，以及 提供有价值的补充信息，以补充从较不标准类型的 结构研究。2)生物小角X射线散射装置(BioSAXS)这项技术 CORE将实施最先进的硬件、软件和专业知识，以支持日益成熟的 需要BioSAXS技术。除了确定蛋白质、核酸和更大分子的形状 在溶液中组装，BioSAXS允许研究人员获得关于全球构象的信息 大分子复合体(如生长因子受体、RNA剪接复合体)和/或 它们的低聚状态的变化具有重要的功能后果。这个核心还将 为有兴趣进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BioSAXS或BioSAXS研究。MacCHESS将提供强大的 行政核心支持这些活动，并将继续教育用户，以及生物医学 研究社区，通过培训和外联核心。总体而言，这些努力将提供独特的 为我们的用户提供在结构生物学领域探索一些最具挑战性的问题的机会 获得结构-功能信息，最终将突出新的治疗靶点并有助于 制定应对疾病的临床策略。

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.