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.高通量筛选核心 (HTS) 为了响应 NIH 分子库和成像路线图，我们已经全面建立了 P50 高吞吐量核心。新的核心代表了多部门的努力和财政支持 与放射科、分子科联合建立来自 P50​​ 基金的核心 生物学与药理学、细胞生物学以及霍华德休斯医学研究所。院长 华盛顿大学医学院以及华盛顿大学西特曼院长 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。该核心是我们的 P50 计划如何实现的一个杰出的持续示例 发挥大学资源，持续激发跨学科分子影像 整个 WU 校园的活动。我们优化了多个机器人协议和物流 我们第一个高通量筛选项目的要求和令人兴奋的数据现已上线 2006 年夏季。Core 可以自动筛选在 96 或 384 平板中培养的细胞 共振峰，可应用于多个研究者发起的分子成像应用 大学社区。这些应用包括： 1) 小分子筛选应用于 WU 研究人员设计的细胞，用于成像和 治疗药物先导。 2) 小分子或肽筛选以鉴定酶抑制剂（针对高优先级 蛋白酶、激酶、磷酸酶等）或蛋白质-蛋白质相互作用的调节剂。 3) 针对人类激酶、磷酸酶和 E3 连接酶的全基因组 siRNA 文库筛选 细胞靶向信号转导、细胞生长或细胞死亡反应。 我们的第一个项目重点是使用新型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类激酶和磷酸酶。击倒策略也正在实施 用于探索细胞周期调节生物发光读数的融合报告基因，Notch 信号传导 途径、MDR1 基因表达调控等相关发现项目。我们很快就会 合并来自化学核心的小分子库。这些直接体现了循环 分子报告核心、化学核心、HTS 核心和 ICMIC 研发之间的协同作用 项目。