Highthroughput Screening Core

最近在阐明肌营养不良和肌肉疾病的机制方面取得了进展 极大地增加了可用于潜在药物治疗的蛋白质靶点的数量。同时， 新的方法增加了可以测试的化合物的数量，以对抗这些 目标。这些趋势共同刺激了采用高通量筛选(HTS)作为 早期药物发现的主要工具。虽然HTS仅应用于有限的一组肌肉 营养不良靶点，这种方法的早期应用已经导致了治疗学的发展 目前正在诊所接受测试。这提高了全世界和加州大学洛杉矶分校的热情 MDTRaC研究人员设计和实施肌营养不良相关药物检测方法 发现号。加州大学洛杉矶分校已经做出了巨大的承诺，在校园内进行HTS筛选，形式是 加州大学洛杉矶分校的MSSR作为促进转化医学的一种机制。然而， 对这一资源的访问目前受到可用的人力、单元模型、专业知识和单元空间的限制 肌肉谱系和肌营养不良相关细胞的扩增和处理。要解决这一限制 我们建议创建一个与肌肉相关的HTS Core，它将利用 MSSR将提供人力、专业知识、空间、资源和指导肌肉细胞和 成纤维细胞培养。在这方面，HTS化验核心将：目标1)在化验开发和 提供可用的肌肉和肌营养不良相关细胞模型；目标2)提供细胞 文化扩展和平台(HTS格式)和MSSR接口服务，目标3)检索和分析 和在MSSR收集的地雷数据；以及AIM 4)协助制定和执行次级方案 铅命中化合物验证的化验。因此，拟议的核心通过利用 现有对校园内已有的HTS技术的巨额投资，并实施 所需的资源和技能

Recent progress in elucidating the mechanisms underlying muscular dystrophy and muscle disease has dramatically increased the number of protein targets available for potential drug treatment. Concurrently, new approaches have increased the number of compounds that can be tested for activity against these targets. Together, these trends have stimulated the adoption of high-throughput screening (HTS) as a primary tool for early-stage drug discovery. While HTS has only been applied to a limited set of muscular dystrophy targets, early application of this approach has already lead to the development of therapeutics currently being tested in the clinic. This has lead to increased enthusiasm worldwide and among UCLA MDTRaC Investigators for designing and implementing muscular dystrophy relevant assays for drug discovery. UCLA has already made a tremendous commitment to HTS screening on campus in the form of the UCLA MSSR as one mechanism by which to facilitate translational medicine, in general. However, access to this resource is currently limited by available manpower, cell models, expertise and space for cell expansion and handling of muscle lineage and muscular dystrophy relevant cells. To address this limitation we propose to create a muscle relevant HTS Core that will utilize the robotics and imaging capabilities of the MSSR and will provide manpower, expertise, space, resources, and guidance on muscle cell and fibroblast culture. In this context the HTS Assay Core will: Aim 1) advise users in assay development and provide access to available muscle and muscular dystrophy relevant cell models; Aim 2) provide cell culture expansion and plating (in HTS format) and MSSR interfacing services, Aim 3) retrieve and analyze and mine data collected at the MSSR; and Aim 4) aid in development and implementation of secondary assays for lead hit compound validation. Thus, the proposed core maximizes impact by leveraging the existing tremendous investment in HTS technology already available on campus and implementing the needed resources and skills to