MLSCN Center at Columbia University

描述(由申请人提供)：位于MLSCN的哥伦比亚中心将根据其在细胞生物学、高内容/高分辨率自动细胞成像和图像分析以及表型分析设计和实施方面的实力和经验而与众不同。在这些现有优势的基础上，我们的中心建议将战略重点放在高通量筛查上，使用细胞和亚细胞水平的表型分析来识别生物活性化合物，这将使我们能够在允许的预算范围内达到或超过RFA规定的筛查里程碑。由于其战略差异化，哥伦比亚中心将在整个MLSCN网络中发挥独特的作用，并使其受益。网络中针对定义的分子靶点进行筛选的姐妹中心将与哥伦比亚大学动态互动，提供二次筛查服务。为了促进这一点并增加价值，哥伦比亚中心将利用其为转介调查人员所实施的分析来创建生物分析的“家庭剧目”。对照这一生物学谱系分析HITS将提供关于生物学水平上的特异性的重要信息，以补充关于化合物在蛋白质/靶水平上的选择性的信息。这类信息对于该网络实现最佳实践至关重要，因为它将限制化学资源的资源集中在最有希望的热门节目上。为了在三年内实现上述目标，哥伦比亚中心将在内部构建为一系列五个功能组件(分析实施、HTS、探针开发、信息学、管理)，每个组件都有明确的目标、里程碑和时间表。每个职能部门将由一名专门的资深科学家领导，项目将由一名专职的项目经理协调：该项目得到了哥伦比亚大学的大力支持，哥伦比亚大学已经为该项目购买了一套最先进的高通量共聚焦细胞成像系统(GE INCell3000)，并将在PI的实验室附近提供空间(约5000 NSF)以及允许中心实现细胞筛选完全自动化所需的资本设备。

DESCRIPTION (provided by applicant): The Columbia Center in the MLSCN will be differentiated on the basis of its strength and experience in cell biology, high content/high resolution automated cellular imaging and image analysis, and phenotypic assay design and implementation. Building on these existing strengths, our Center proposes a strategic focus on high throughput screening using phenotypic assays at the cellular and subcellular levels to identify bioactive compounds, which will enable us to meet or exceed the screening milestones mandated in the RFA within the scope of the allowed budget. Because of its strategic differentiation, the Columbia Center will perform uniquely within and to the benefit of the MLSCN network as a whole. Sister centers in the network which screen against defined molecular targets will dynamically interact with Columbia for secondary screening services. To facilitate this and to add value, the Columbia Center will draw on the assays it implements for referring investigators to create a "house repertoire" of biological assays. Profiling of hits against this repertoire of biology will provide important information on specificity at the biological level to complement information on the compound's selectivity at the protein/target level. This kind of information will be critical for the network to achieve best practice by focusing what will be limiting chemistry resources on the most promising hits. To accomplish the above goals in three years, the Columbia Center will be structured internally as a series of five functional components (assay implementation, HTS, probe development, informatics, management) each with defined goals, milestones and timelines. Each function will be led by a dedicated senior scientist, and the project will be coordinated by a dedicated project manager: The project is strongly supported by Columbia, which has already purchased a state-of-the-art highthroughput confocal cell imaging system (GE INCell3000) for the project, and will provide space (approx 5,000 nsf) adjacent to the PI's laboratory as well capital equipment needed to allow full automation of cellular screening at the Center.