High Throughput Screening

高通量筛选核心设施（HTSCF）成立于2003年，以支持该机构的 化学生物学和功能基因组学的发展。HTSCF正在进行的使命继续支持 这样的努力。生物活性化合物被用作探测生物过程的化学工具。的 新分子的鉴定需要广泛的工具，包括稳健的测定、大量的 化学品、HTS技术以及命中验证和表征步骤方面的知识。HTSCF已 现代机器人，定制筛选数据管理数据库，化学筛选库，RNAi 筛选库、检测开发和工业化专业知识、筛选数据分析和 管理核心配备了两个定制的线性轨道机器人平台， 分配器、微量滴定板读数器、自动显微镜以及其他仪器， 基于靶的和基于细胞的测定被常规地进行。筛选数据采集和 管理是通过一套定制的软件来处理的。复合库已增长到400 K 化学品;并含有各种天然产品。RNAi文库也已经发展到包括 siRNA和shRNA能力覆盖22 K基因。单个shRNA发夹的甘油储备液是 作为服务提供。这项工作促进的重要工作的一个例子是对突变体的筛选 Varmus实验室在人肺癌细胞系中的EGFR。筛选工作导致了识别和 表征了克服突变的四类小分子。广泛的服务范围 过去，HTSCF提供的合作工作支持了48名研究人员的研究 年在过去的赠款期间，核心小组的工作为27份研究人员的出版物做出了贡献。 8个研究项目。

The High-throughput Screening Core Facility (HTSCF) was established in 2003 to support the Institution's growth in chemical biology and functional genomics. The HTSCF's ongoing mission continues to support such efforts. Bioactive compounds are used as chemical tools to probe biological processes. The identification of novel molecules requires a broad range of tools including robust assays, large collections of chemicals, HTS technologies, and knowledge in hit validation and characterization steps. The HTSCF has modern robotics, custom built screening data management databases, chemical screening libraries, RNAi screening libraries, assay development and industrialization expertise, screening data analysis and management. The Core is equipped with two custom-built linear track robotic platforms harboring several dispensers, microtiter plate readers, automated microscopes among other instrumentation enabling both invitro target based and cell based assays to be routinely performed. Screening data acquisition and management is handled through a suite of custom built software. The compound library has grown to 400K chemicals; and contains a wide variety of natural products. The RNAi libraries have also grown to include both siRNA and shRNA capabilities covering 22K genes. Glycerol stocks of individual shRNA hairpins are provided as a service. One example of important work facilitated by this work was a screen against mutant EGFR in human lung cancer cell lines by the Varmus lab. The screening efforts led to the identification and characterization of four classes of small molecules overcoming the mutations. The broad range of services and collaborative work provided by the (HTSCF) has supported the research of 48 investigators in the past year. During the past grant period the work of the Core has contributed to 27 publications of researchers from 8 research programs.