Core C: Molecualr Imaging High Throughput Screening Core (HTS)

核心 C：分子成像高通量筛选核心 (HTS)

• 批准号: 7287036
• 负责人: HELEN M PIWNICA-WORMS
• 金额: $ 18.79万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-28 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7287036
• 关键词: ABCB1 gene; Biological Assay; Bioluminescence; Blood Circulation; Cancer Center; Cell Cycle Regulation; Cell Death; Cells; Cellular biology; Chemistry; Communities; Cultured Cells; Data; Endopeptidases; Enzyme Inhibitor Drugs; Enzyme Inhibitors; Facility Construction Funding Category; Funding; Gene Expression; Genome; Housing; Human; Human Resources; Image; Image Analysis; Institutes; Libraries; Liquid substance; Luciferases; Medical; Molecular; Molecular Bank; Molecular Biology; Notch Signaling Pathway; Peptide Hydrolases; Peptides; Pharmaceutical Preparations; Pharmacology; Phosphoric Monoester Hydrolases; Phosphotransferases; Process; Protocols documentation; Radiology Specialty; Range; Regulation; Reporter; Research Personnel; Research Project Grants; Resource Development; Resources; Robot; Robotics; Science; Screening procedure; Signal Transduction; Site; Small Interfering RNA; Specialized Center; TNFRSF5 gene; Therapeutic; United States National Institutes of Health; Universities; Washington; air filter; cell growth; cellular engineering; day; falls; high throughput screening; in vivo Cellular and Molecular Imaging Centers; innovation; instrument; knock-down; medical schools; molecular imaging; novel; pressure; protein phosphatase inhibitor-2; protein protein interaction; research and development; research study; response; small molecule; small molecule libraries; ubiquitin-protein ligase

A.3.iii. High Throughput Screening Core (HTS) In response to the NIH Roadmap to Molecular Libraries and Imaging, we have fully established a P50 High Throughput Core. The new Core represents a multi-departmental effort with fiscal support for establishing the Core coming from P50 funds in combination with the Departments of Radiology, Molecular Biology & Pharmacology, and Cell Biology as well as the Howard Hughes Medical Institute. The Dean of Washington University School of Medicine as well as the Director of the Washington University Siteman Cancer Center joined our effort with the commitment of additional funds for further development of the resource. This Core serves as an outstanding on-going example of how our P50 program has leveraged university resources and continues to stimulate interdisciplinary molecular imaging activity throughout the WU campus. We have optimized several robotic protocols and logistical requirements for our first projects in high throughput screening and exciting data are now coming on-line during the summer of 2006. The Core allows for automated screening of cells cultured in 96 or 384 plate formants and can be applied to multiple investigator-initiated molecular imaging applications throughout the university community. The applications include: 1) small molecule screens applied to cells engineered by WU investigators for imaging and therapeutic drug leads. 2) small molecule or peptide screens to identify enzyme inhibitors (directed against high priority proteases, kinases, phosphatases, etc.), or modulators of protein-protein interactions. 3) genome-wide siRNA library screens against kinases, phosphatases and E3-ligases in human cells targeting signal transduction, cell growth or cell death responses. Our first projects are focused on use of the novel split luciferase complementation imaging platform developed in the Molecular Reporter Core for analysis of protein-protein interactions using siRNA libraries against all known expressed human kinases and phosphatases. Knock-down strategies are also being used to explore fusion reporters for bioluminescence readouts of cell cycle regulation, the Notch signaling pathway, and regulation of MDR1 gene expression and other related discovery projects. We will soon be incorporating small molecule libraries from the Chemistry Core. These directly demonstrate the cycle of synergies between the Molecular Reporter Core, the Chemistry Core, the HTS Core and ICMIC R&D Projects.

A.3.III.高吞吐量筛选核心(HTS) 作为对NIH分子图书馆和成像路线图的响应，我们已经完全建立了 P50高吞吐量核心。新的核心代表了多部门的努力，并提供了财政支持 结合放射科、分子科建立P50经费核心 生物学和药理学、细胞生物学以及霍华德·休斯医学院。香港中文大学教务长 华盛顿大学医学院以及华盛顿大学西特曼主任 癌症中心加入了我们的努力，并承诺提供额外资金，以进一步发展 资源。这一核心是我们的P50计划如何具有 利用大学资源，继续促进跨学科分子成像 活动遍及整个吴校区。我们已经优化了几个机器人协议和后勤 我们在高通量筛选和令人兴奋的数据方面的首批项目需求现已上线 在2006年夏天。核心允许自动筛选培养在96或384平板中的细胞 共振峰，可应用于研究人员发起的多个分子成像应用 大学社区。这些应用程序包括： 1)小分子屏幕应用于吴研究员设计的细胞成像和 治疗性药物线索。 2)筛选小分子或多肽以识别酶抑制剂(针对高优先级 蛋白水解酶、激酶、磷酸酶等)或蛋白质-蛋白质相互作用的调节物。 3)全基因组siRNA文库筛选人类的激酶、磷酸酶和E3-连接酶 细胞以信号转导、细胞生长或细胞死亡反应为靶点。 我们的第一个项目集中在使用新的分裂荧光素酶互补成像平台 在分子报告核心中开发，用于使用siRNA文库分析蛋白质-蛋白质相互作用 对抗所有已知表达的人蛋白激酶和磷酸酶。击倒战略也在进行中 用于探索融合报告生物发光读数的细胞周期调控，Notch信号 途径、多药耐药基因表达的调控以及其他相关发现项目。我们很快就会 整合了化学核心的小分子文库。这些都直接证明了 分子报告核心、化学核心、高温超导核心与ICMIC研发的协同效应 项目。