High Throughput Screening

高通量筛查核心设施(HTSCF)于2003年建立，以支持研究所的 化学生物学和功能基因组学的发展。HTSCF的持续任务将继续支持 这样的努力。生物活性化合物被用作探索生物过程的化学工具。这个 鉴定新分子需要广泛的工具，包括可靠的分析、大量的 化学品、HTS技术以及HIT验证和表征步骤方面的知识。HTSCF已经 现代机器人、定制筛选数据管理数据库、化学筛选库、RNAi 筛选文库、分析开发和产业化专业知识、筛选数据分析和 管理层。核心配备了两个定制的线性轨道机器人平台，其中 分配器、微量平板阅读器、自动显微镜以及其他能够实现体外培养的仪器 常规进行基于靶点和基于细胞的分析。筛选数据采集和 管理是通过一套定制的软件进行的。化合物库已增长到400K 化学物质；并含有各种各样的天然产品。RNAi文库也已发展到包括 SiRNA和shRNA都具有覆盖22K基因的能力。单个shRNA发夹的甘油库存为 作为一种服务提供的。这项工作促进了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。筛查工作导致了身份识别和 四类克服突变的小分子的表征。广泛的服务范围 过去，(HTSCF)提供的合作工作支持了48名调查人员的研究 年。在过去的赠款期间，核心的工作为27份研究人员的出版物作出了贡献 来自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.