La Jolla Interdisciplinary Neuroscience Center Cores - Chemical Core

化学文库筛选芯 一、主要目标和方向 化学图书馆筛选(CLS)设施核心的任务是提供新的化学工具 并向神经科学研究人员开发潜在的药物。小分子筛选技术在生物医学研究中的应用 最近文献中的一些报告说明了解决生物学问题的方法(见引文 (见下文)。预计这条研究路线将提供化验和化学投入到 开发治疗神经疾病的新铅分子的流水线。自.以来 高通量筛查在学术机构并不广泛使用，这一设施将提供一种新的 和独特的方法来表征涉及许多方面的蛋白质和信号通路 神经发育和神经疾病。这个核心将设在伯纳姆研究所 用于医学研究(BIMR)，并代表现有核心的扩展 由BIMR癌症中心开发，但神经科学家目前还不能使用。BIMR‘s 对这笔赠款的捐款来自机构购买设备，包括机器人 筛选设施、高通量显微镜和化学图书馆，价值远远超过200万美元。 拟议的NIH蓝图神经科学核心中心拨款将促进和鼓励使用这一技术 神经学家在索尔克BIMR的La Jolla Torrey Pines台地进行化学筛选的核心 斯克里普斯研究所(TSRI)和加州大学圣地亚哥分校(UCSD)。 核心设施将提供化学图书馆，包括一条集成的机器人生产线，带有自动 培养箱，平板旅馆和尖端装载器，用于带有读数的生化分析，包括FRET， 荧光偏振和发光。此外，还提供完整的高内容筛选生产线 这包括机器人处理液体和盘子，自动保温箱，清洁室里的盘子旅馆 用于基于细胞的分析的环境。图像采集能力包括Beckman Coulter和GE 带有机器人平板送料的自动显微镜。复杂的软件包用于 自动跟踪板材和化合物、化学信息学和图像分析。一般来说，有两个 用以下术语进行各种筛分：(I)HTS是高通量筛分， 通常用于基于细胞的分析的生化屏幕或平板阅读器屏幕；(Ii)HCS高 内容筛选，用于细胞分析的基于图像的筛选，即使用图像的分析类型 细胞分析。生化和基于细胞的筛查的所有方面都有专家协助， 包括自动化工程、药物化学、图像采集、算法工程和 分析。CLS设施位于圣地亚哥化学基因组中心内的BIMR (SDCGC)，它也是NIH资助的多重图书馆的9个校外中心之一 筛选中心网络。该中心由马克·默科拉博士指导，史蒂夫博士管理 瓦西里。Mercola博士还指导SDCGC的化验开发和化验实施单位。 目前，CLS设施以按存储容量使用计费的方式运行，以支持BIMR的成员 由BIMR癌症中心支持赠款(CCSG)赞助的癌症中心。因为. 需求很大，它只向巨蟹座的成员提供非常有限的和偶尔的服务 研究社区不在BIMR，而且几乎无法接触到神经科学家。这样做的主要目标是 申请是为CLS内的人员提供工资支持和便利 神经科学研究人员关于La Jolla Torrey的跨学科、协作研究项目 松树台地。

CHEMICAL LIBRARY SCREENING CORE 1. MAIN OBJECTIVES AND DIRECTIONS The mission of the Chemical Library Screening (CLS) Facility Core is to provide new chemical tools and potential drug develop to Neuroscience investigators. The utility of small molecule screening for solving problems in biology is illustrated by a number of recent reports in the literature (see citations below). It is also anticipated that this route of study will provide assay and chemical inputs into the pipeline for the development of new lead molecules for the treatment of neurological disorders. Since high-throughput screening is not widely available at academic institutions, this facility will provide a new and unique approach toward characterizing proteins and signaling pathways involved in many aspects of neural development and neurologic disease. This Core will be located at the Burnham Institute for Medical Research (BIMR) and represents an expansion of an existing Core that was developed by BIMR's Cancer Center, but is not available to neuroscientists at this time. BIMR's contribution to this grant is represented by the institutional purchase of equipment, including the robotic screening facility, high-throughput microscopes, and chemical libraries, valued at well over $2 million. The proposed NIH Blueprint Neuroscience Core Center Grant will facilitate and encourage use of this Chemical Screening Core by neuroscientists on the La Jolla Torrey Pines Mesa at BIMR, The Salk Institute, The Scripps Research Institute (TSRI), and the University of California, San Diego (UCSD). The Core facility will offer chemical libraries, including an integrated robotic line with an automated incubator, plate hotel and tip loader, for biochemical assays with readouts including FRET, fluorescence polarization, and luminescence. Also offered is a complete high content screening line that includes robotics for liquid and plate handling, automated incubator, plate hotel in a clean-room environment for cell-based assays. Image-acquisition capabilities include Beckman Coulter and GE automated microscopes with robotic plate feeding. Sophisticated software packages are used for automated tracking of plates and compounds, cheminformatics, and image analysis. In general, two kinds of screens are performed with the following nomenclature: (i) HTS is high throughput screening, typically used for biochemical screens or plate-reader screens of cell-based assays; (ii) HCS is high content screening, used for image-based screens of cell assays, i.e. type of assays that use image analysis of cells. Expert assistance is available for all aspects of biochemical and cell-based screens, including automation engineering, medicinal chemistry, image acquisition, algorithm engineering and analysis. The CLS facility is located at BIMR within the San Diego Chemical Genomics Center (SDCGC), which also operates as one of the 9 NIH funded extramural centers of the Multiple Library Screening Center Network. The center is directed by Dr. Mark Mercola and managed by Dr. Steve Vasile. Dr. Mercola also directs Assay Development and Assay Implementation units of the SDCGC. Currently, the CLS facility operates as a charge-back basis to support members of the BIMR Cancer Center under the auspices of the BIMR Cancer Center Support Grant (CCSG). Because of heavy demand, it has offered only very limited and occasional service to members of the Cancer research community not at BIMR, and virtually no access to neuroscientists. The primary goal of this application is to provide salary support for personnel within CLS to support and facilitate interdisciplinary, collaborative research projects of neuroscience investigators on the La Jolla Torrey Pines Mesa.