CORE--BIOINFORMATION AND CELL-BASED ASSAY

核心——生物信息和细胞分析

• 批准号: 6928835
• 负责人: ANDREAS VOGT
• 金额: $ 14.71万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6928835
• 关键词: antineoplastics; bioinformatics; biomedical facility; cells; chemical models; combinatorial chemistry; drug discovery /isolation; growth inhibitors; high throughput technology; information retrieval; microtubules; molecular /cellular imaging; tubulin

The major goals of the Bioinformation and Cell-based Assay Core are to provide computational resources to aid in the design, analysis, and therapeutic optimization of dual specificity phosphatase inhibitors and antimitotic agents and to perform cell-based, high-information content analyses on prioritized compounds from other subprojects to aid in the selection of candidates for preclinical evaluation by Core C. The Core thus assumes a central location between the chemistry, biology, and preclinical assay groups. To achieve these goals, the Core will perform four main functions: 1) data warehousing; 2) data mining and molecular modeling 3) high-information content, cell-based analyses and; 4) in vitro analysis of microtubule perturbing agents. Data mining will be accomplished through a series of hierarchical SAR and QSAR techniques to analyze the large and diverse learning sets of information associated with the two targeted biological activities from other subprojects. Cell-based analyses will make extensive use of the Core's existing high-throughput, cell-based assay and analysis capabilities including automated liquid handling, fluorescence-based multiparametric assays, and automated image acquisition and batch image processing. The Specific Tasks of this Core are 1) To provide informatics for the Program Project by maintaining a central, electronic, program-accessible repository of chemical and biological data; 2) To facilitate the identification of new lead structures by creating models of molecular requirements for prioritized compounds through in silico screening of in-house combinatorial libraries or outside compound databases. 3) To perform multiparametric analyses, including gowth inhibition studies, of prioritized compounds in intact cells, either alone or in combination with existing chemotherapeutic agents. 4) To evaluate the in vitro tubulin/microtubule perturbing activities of library components.

生物信息和基于细胞的检测核心的主要目标是提供计算资源，以帮助双特异性磷酸酶抑制剂和抗有丝分裂剂的设计、分析和治疗优化，并根据优先顺序进行基于细胞的高信息内容分析。来自其他子项目的化合物，以帮助选择核心 C 进行临床前评估的候选化合物。因此，核心处于化学、生物学和临床前检测组之间的中心位置。为了实现这些目标，核心将执行四个主要功能：1）数据仓库； 2) 数据挖掘和分子建模 3) 高信息含量、基于细胞的分析； 4)微管扰动剂的体外分析。数据挖掘将通过一系列分层SAR和QSAR技术来完成，以分析与其他子项目的两个目标生物活动相关的大量且多样化的学习信息集。基于细胞的分析将广泛利用 Core 现有的高通量、基于细胞的测定和分析功能，包括自动液体处理、基于荧光的多参数测定以及自动图像采集和批量图像处理。该核心的具体任务是 1) 通过维护一个中央、电子、程序可访问的系统，为计划项目提供信息学 化学和生物数据存储库； 2) 通过内部组合库或外部化合物数据库的计算机筛选，创建优先化合物的分子需求模型，以促进新先导结构的识别。 3) 对完整细胞中的优先化合物进行多参数分析，包括生长抑制研究，无论是单独使用还是与现有化疗药物组合使用。 4) 评估文库成分的体外微管蛋白/微管扰动活性。