MLSCN Center at Columbia University(RMI)

描述（由申请方提供）：MLSCN的哥伦比亚中心将根据其在细胞生物学、高内容/高分辨率自动化细胞成像和图像分析以及表型试验设计和实施方面的实力和经验进行区分。在这些现有优势的基础上，我们的中心提出了一个战略重点，即在细胞和亚细胞水平上使用表型分析进行高通量筛选，以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规定的筛选里程碑。由于其战略差异，哥伦比亚中心将在MLSCN网络内发挥独特作用，并使整个MLSCN网络受益。网络中针对确定的分子靶标进行筛选的姐妹中心将与哥伦比亚进行动态互动，以提供二级筛选服务。为了促进这一点，并增加价值，哥伦比亚中心将借鉴其实施的检测方法，为转介研究者创建一个生物检测的“内部库”。针对该生物学库的命中分析将提供关于生物学水平上的特异性的重要信息，以补充关于蛋白质/靶标水平上的化合物选择性的信息。这类信息对于网络实现最佳实践至关重要，因为它将限制化学资源的重点放在最有希望的命中上。为了在三年内实现上述目标，哥伦比亚中心的内部结构将由一系列五个功能组件（检测试剂盒实施、HTS、探针开发、信息学、管理）组成，每个组件都有明确的目标、里程碑和时间表。每个职能将由一名专职的高级科学家领导，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的大力支持，哥伦比亚已经购买了最先进的高通量共聚焦细胞成像系统（GE INCell 3000），并将提供空间（约5，000 nsf），毗邻PI的实验室，以及资本设备，需要允许在该中心的细胞筛查的完全自动化。

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.