Pittsburgh Molecular Libraries Screening Center(RMI)

描述（由申请人提供）：本申请拟建立一个分子文库筛选中心（UP-MLSC），利用匹兹堡大学现有的和新的空间和设施，成员包括匹兹堡大学、卡内基梅隆大学和桑迪亚国家实验室。UPMLSC的总体目标是开发、实施和优化强大的光学方法，用于检测、表征和细化具有所需生物学和药理学特性的小分子，这些小分子可用于MLSCN指导小组指定的无细胞、基于细胞和基于模型生物的检测。UPMLSC的目标将是(a)验证用于高通量筛选的分析，(b)将这些分析与二级分析和信息学一起使用，以识别化学文库中的活性小分子，(c)促进这些分析在全国范围内的使用，(d)传播有关化合物活性的信息，以及(e)协助进一步优化先导化合物。我们打算利用和扩大中心成员在分析实施、高通量和高含量筛选、组合化学合成和信息学方面记录的现有互动优势。我们为UP-MLSC精心挑选了成员，因为他们在上述核心领域的专业知识，并预期将向中心提交潜在的分析。此外，我们已经招募了在设计和开发新型荧光探针方面的专家，这些荧光探针可能有助于实施新的HTS检测，以及在果蝇和斑马鱼的检测开发方面有经验的个人，这些人将成为UP-MLSC中基于生物体的检测的模型。

DESCRIPTION (provided by applicant): This application proposes to establish a Molecular Libraries Screening Center (UP-MLSC) exploiting existing and new space and facilities at the University of Pittsburgh, with membership from the University of Pittsburgh, Carnegie Mellon University and Sandia National Laboratories. The overall objective of the UPMLSC will be to develop, implement, and optimize robust, optical methods for the detection, characterization, and refinement of small molecules with desired biological and pharmacological properties in cell-free, cell-based, and model organism-based assays assigned by the MLSCN Steering Group. The goals of the UPMLSC will be (a) to validate assays for use in high throughput screening, (b) to use these assays with secondary assays and informatics to identify active small molecules from chemical libraries, (c) to facilitate the use of these assays nationally, (d) to disseminate information about compound activity, and (e) to assist in the further optimization of the lead compounds. We intend to exploit and expand the documented existing interactive strengths of the Center members in assay implementation, high throughput and high content screening, combinatorial chemical synthesis, and informatics. We have carefully selected members for the UP-MLSC because of their expertise in the above-mentioned Core areas and in anticipation of potential assays that will be submitted to the Center. Moreover, we have recruited individuals who are expert in the design and development of novel fluorescent probes that may be useful in implementing new HTS assays, and individuals who have experience with assay development with Drosophila and zebrafish, which will be the models for organism-based assays in the UP-MLSC.