Gene Regulation E.coli Database Integrated Modeling

基因调控大肠杆菌数据库集成建模

• 批准号: 7107847
• 负责人: Julio Collado-Vides
• 金额: $ 21.09万
• 依托单位: CENTER FOR GENOMIC SCIENCES
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7107847
• 关键词: Escherichia coli k12; bacterial genetics; bacterial proteins; biological signal transduction; biological transport; computer simulation; functional /structural genomics; genetic models; genetic regulation; genetic regulatory element; genetic transcription; informatics; microorganism growth; microorganism metabolism; microorganism resource /registry; model design /development; molecular biology information system

DESCRIPTION (provided by applicant): A major challenge in post-genomic biology is the understanding of the complex molecular internal machinery of the cell. A fundamental component in the machinery to take decisions is the regulatory network of transcription initiation. The purpose of this application is to enhance the major annotation project on transcriptional regulation and operon organization of the model organism Escherichia coil K-12. This project is a conceptual continuation and expansion of a previous grant supporting the annotation work enriching RegulonDB. In addition to continuing literature curation, we propose to perform an exhaustive mapping of all possible missing promoter sites in the genome, as well as to perform several theoretical analyses of the regulatory network, together with simulations and comparisons with microarray data performed in other laboratories. We plan to complement literature knowledge with computational predictions, and to actively search for the missing links that will permit us to put together transcription, transport, signal transduction and metabolism, taking advantage of several existing databases. We will determine how much this cellular knowledge is consistent with the large amounts of microarray experiments performed in several laboratories. These comparisons require building several computational and chemical models of regulatory simple and complex interactions determining gene expression, as well as their consequences in the overall cellular network (transport, signal transduction and metabolism). We will analyze the network in modules, motifs, and maps, using different mathematical criteria based on the statistical properties of the network connectivity, as well as on biological knowledge of conditions and microarray experiments. Finally, we intend to perform low-resolution discrete simulations of the dynamics of the network, as well as detailed stochastic modeling of selected maps and subcomponents of the network. Modeling and its comparison with experiments shall enhance the overall quality and depth of the classical and active annotation of the regulatory network of the best known and studied single cell organism. Having a better understanding of a whole cell, shall provide an important contribution to basic biology and thus to the foundations to understand health and disease.

描述（由申请人提供）：基因组生物学后的主要挑战是对细胞复杂分子内部机械的理解。决定决定的机械中的基本组成部分是转录启动的监管网络。本应用的目的是增强模型有机体Escherichia Coil K-12的主要注释项目和操纵组织组织。该项目是支持注释工作的先前赠款的概念延续和扩展。除了持续的文献策划外，我们还建议对基因组中所有可能缺失的启动子站点进行详尽的映射，并对监管网络进行多种理论分析，并与其他实验室中执行的微阵列数据进行模拟和比较。我们计划将文献知识与计算预测相辅相成，并积极寻找丢失的链接，这些链接将使我们能够利用几个现有数据库，从而将转录，传输，信号转导和代谢汇总在一起。我们将确定这种细胞知识与在几个实验室中进行的大量微阵列实验一致。这些比较需要建立几种调节性简单和复杂相互作用的计算和化学模型，以决定基因表达，并在整个细胞网络（传输，信号转导和代谢）中的后果。我们将根据网络连接的统计特性以及条件和微阵列实验的生物学知识，使用不同的数学标准在模块，图案和地图中分析网络。最后，我们打算对网络动力学进行低分辨率离散模拟，以及对网络所选地图和子组件的详细随机建模。建模及其与实验的比较应提高最著名和研究的单细胞生物的调节网络的经典和主动注释的总体质量和深度。对整个细胞有更好的了解，应为基本生物学以及基础以了解健康和疾病的基础提供重要贡献。