STRUCTURAL BIOLOGY

结构生物学

基本信息

批准号：
8378393
负责人：
ROBERT Colin LIDDINGTON
金额：
$ 22.57万
依托单位：
SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-05-21 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8378393
关键词：
Binding Biological Biology Budgets Calorimetry Cancer Center Cancer Center Support Grant Cell Nucleus Cells Chemicals Computer software Crystallization Crystallography DNA Data Collection Development Equipment Funding Future Human Resources Image Individual Insecta Institutes Investments Kinetics Laboratories Ligands Mammalian Cell Maps Measurement Measures Mechanics Molecular Nature Optics Paper Peer Review Play Process Production Protein Dynamics Proteins Publications RNA Research Research Personnel Resolution Resource Sharing Resources Robot Roentgen Rays Role Sampling Scanning Science Scientist Screening procedure Services Shapes Site Source Structure System Techniques Technology Thermodynamics Titrations Training Walking Work anticancer research base cell behavior cell motility detector drug discovery experience inhibitor/antagonist instrument instrumentation large scale production macromolecule molecular size operation programs protein expression protein purification small molecule stopped-flow fluorescence structural biology three dimensional structure

项目摘要

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.

结构生物学共享资源将晶体学、核磁共振和蛋白质生产结合在一起由 Liddington 博士担任科学总监和两名设施总监/经理对单个设施进行分析谁监督日常运营。这次合并带来了两种互补的技术以原子分辨率确定生物大分子的 3 维结构用于蛋白质大规模生产和生物物理表征的设施、技术由于其费用和复杂性，各个癌症中心实验室都可以使用。这些发展创造了一种无缝资源，正在改变科学家的能力结构生物学经验，将结构和结构功能研究以及化学研究结合起来生物学纳入他们的研究计划。扩建后的设施已满足 40 多名癌症患者的需求过去几年中心调查人员。研究所对重大设备进行了升级改造晶体学，包括配备齐全的高亮度发生器，可在两个端口上收集数据配备结晶机器人和存储/成像“酒店”；用于 600 MHz NMR 仪器的新型冷冻探针以及一款新的“直接”400 MHz 仪器，经过优化可快速调谐到不同的核和高通量更换样品；以及用于大规模蛋白质表达和纯化的完整实验室套件细菌、昆虫和哺乳动物细胞，以及用于生物物理分析的最先进的仪器，包括分析超速离心机、差示扫描和等温滴定量热法以及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过去资助期间的工作至少发表了 83 篇同行评审论文，其中 5 篇发表在 Nature、Cell 或 Science，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集成到药物发现工作；额外的仪器来测量蛋白质-小分子的结合动力学相互作用，并测量分子内部和分子之间的机械力及其与分子之间的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 139,456 美元的 CCSG 支持，占 12% 预计的结构生物学运营预算总额。