MLSCN Center at Columbia University

哥伦比亚大学 MLSCN 中心

• 批准号: 7076249
• 负责人: JAMES ROTHMAN
• 金额: $ 286.92万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7076249
• 关键词: NIH Roadmap Initiative tag; biotechnology; cheminformatics; confocal scanning microscopy; cooperative study; drug discovery /isolation; functional /structural genomics; high throughput technology; molecular probes; proteomics

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.

描述（由申请人提供）：MLSCN 的哥伦比亚中心将因其在细胞生物学、高内涵/高分辨率自动细胞成像和图像分析以及表型测定设计和实施方面的实力和经验而脱颖而出。基于这些现有优势，我们中心提出战略重点是使用细胞和亚细胞水平的表型测定来鉴定生物活性化合物的高通量筛选，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。由于其战略差异化，哥伦比亚中心将在整个 MLSCN 网络内发挥独特作用并造福于整个 MLSCN 网络。网络中针对特定分子靶标进行筛查的姐妹中心将与哥伦比亚动态互动，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诊研究人员实施的检测来创建生物检测的“内部库”。针对这一生物学库的命中分析将提供有关生物学水平特异性的重要信息，以补充有关蛋白质/靶标水平上化合物选择性的信息。此类信息对于网络通过将限制化学资源集中在最有希望的命中上来实现最佳实践至关重要。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（检测实施、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高级科学家领导，该项目将由一名专门的项目经理进行协调：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最先进的高通量共聚焦细胞成像系统（GE INCell3000），并将提供与 PI 实验室相邻的空间（约 5,000 nsf）以及允许在中心实现细胞筛查完全自动化所需的资本设备。