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.

TTIE结构生物学共享资源带来了Crystallograpfiy，NMR和蛋白质生产的togethier Crystallograpfiy＆分析单个设施，与利丁顿博士为科学总监和两位设施董事/经理负责日常运营的人。这次合并带来了两种补充技术确定原子分辨率生物大分子的三维结构以及蛋白质的大规模生产和生物物理表征的设施，不是不是由于其费用和复杂性，可在个别癌症中心实验室中使用。这些发展创造了一种无缝的资源，该资源正在改变科学家的能力结构生物学的经验，结合了结构和结构功能研究以及化学生物学进入他们的研究计划。扩展的设施已经满足了40多个癌症的需求过去几年中心的调查人员。该研究所提供了主要设备升级晶体学，包括一个高光彩生成器，配备了两个端口的数据收集，带有结晶机器人和存储/成像“酒店”； 600 MHz NMR仪器的新的冷冻探针以及一种优化的新“步行” 400 MHz仪器，用于快速调整到不同的核和高通量改变样本；以及一个完整的实验室套件，用于大规模蛋白质表达和纯化细菌，昆虫和哺乳动物细胞以及最新的仪器进行生物物理分析，包括分析性超速离心，差分扫描和等温滴定量热法和停止流量荧光光谱仪，用于测量分子大小，形状，折叠的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者的在过去的资金期间工作，导致至少有83份同行评审的论文，其中包括5篇自然，细胞或科学以及40多个关于结构生物学各个方面和的评论文章结构功能研究。未来的优先事项包括结晶机器人设施的完整整合到毒品发现工作；测量蛋白质 - 小分子的结合动力学的其他仪器相互作用，并测量分子内部和之间的机械力及其与它们与它们的相互作用在细胞迁移等过程中的化学力；并在真核蛋白表达中进一步升级和纯化系统。总体而言，第一年要求提供139,456美元的CCSG支持，占12％预计结构生物学运营预算的总数。