STRUCTURAL BIOLOGY

结构生物学共享资源将更多的结晶、核磁共振和蛋白质生产结合在一起 对单一设施的分析，利丁顿博士担任其科学主任和两名设施主任/经理 他们负责监督日常运作。这一合并为以下两种互补技术带来了 在原子分辨率下测定生物大分子的三维结构 用于蛋白质的大规模生产和生物物理表征的设施，这些技术不是 由于其费用和复杂性，可在各个癌症中心实验室使用。这些 发展创造了一种无缝资源，正在改变科学家的能力，而这几乎没有先例 结构生物学方面的经验，包括结构和结构-功能研究以及化学 在他们的研究项目中加入了生物学。扩建后的设施已经满足了40多名癌症患者的需求 中心的调查人员在过去几年里。该研究所在#年提供了主要设备升级。 结晶学，包括一台配备齐全的高亮度发生器，可同时在两个端口上收集数据 配备结晶机器人和存储/成像“旅馆”；用于600 MHz核磁共振仪器的新低温探头 和一种新的“无人值守”的400 MHz仪器，为快速调谐到不同的原子核和高通量而优化 和一套完整的实验室套件，用于大规模表达和纯化 细菌、昆虫和哺乳动物细胞，以及最先进的生物物理分析仪器， 包括分析型超速离心机、差示扫描量热仪和恒温滴定量热仪. 停流荧光光谱仪，用于测量分子大小、形状、折叠完整性和 热力学和动力学结合常数。该资源直接支持癌症中心研究人员的 在过去的供资期间所做的工作导致发表了至少83篇同行评审论文，其中5篇发表于 自然、细胞或科学，以及40多篇关于结构生物学和 结构-功能研究。未来的优先事项包括将结晶机器人设施完全整合到 药物发现工作.测量蛋白质-小分子结合动力学的附加仪器 相互作用，并测量分子内部和分子之间的机械力及其相互作用 细胞迁移等过程中的化学力；以及真核蛋白表达的进一步升级 和净化系统。总体而言，第一年需要提供139,456美元的CCSG支持，占12% 预计结构生物学业务预算总额。

Ttie Structural Biology Shared Resource brings togethier Crystallograpfiy, NMR, and Protein Production & Analysis into a single facility, with Dr. Liddington as its Scientific Director and two Facility Directors/Managers who oversee day-to-day operations. This merger has brought the two complementary techniques for determining 3-dimensional structures of biological macromolecules at atomic resolution together with facilities for the large-scale production and biophysical characterization of proteins, technologies that are not available in individual Cancer Center laboratories owing to their expense and complexity. These developments have created a seamless Resource that is transforming the ability of scientists with little prior experience in structural biology to incorporate structural and structure-function studies as well as chemical biology into their research programs. The expanded facility has served the needs of more than 40 Cancer Center investigators over the last few years. The Institute has provided major equipment upgrades in crystallography, including a high brilliance generator fully equipped for data collection on two ports, together with a crystallization robot and storage/imaging "hotels"; a new cryoprobe for the 600 MHz NMR instrument and a new "walk-up" 400 MHz instrument optimized for rapidly tuning to different nuclei and high-throughput sample-changing; and a complete laboratory suite for large-scale protein expression and purification in bacterial, insect and mammalian cells, together with state-of-the-art instrumentation for biophysical analysis, including an Analytical Ultracentrifuge, Differential Scanning and Isothermal Titration Calorimetry and stopped-flow fluorescence spectrometer for measurement of molecular size, shape, folded integrity, and thermodynamic and kinetic binding constants. The Resource directly supported Cancer Center investigator's work in the past funding period that led to the publication of at least 83 peer-reviewed papers, including 5 in Nature, Cell or Science, as well as more than 40 review articles on various aspects of structural biology and structure-function studies. Future priorities include the full integration of the crystallization robot facility into drug discovery efforts; additional instrumentation to measure binding kinetics of protein-small molecule interactions, and to measure mechanical forces within and between molecules and their interplay with chemical forces in processes such as cell migration; and further upgrades in eukaryotic protein expression and purification systems. Overall, $139,456 in CCSG support is requested in the first year, representing 12% of the total projected Structural Biology operating budget.