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: 6811226
• 负责人: Julio Collado-Vides
• 金额: $ 21.6万
• 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/6811226
• 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）：后基因组生物学的一个主要挑战是理解细胞复杂的分子内部机制。决策机制的一个基本组成部分是转录起始的调控网络。本申请的目的是加强模式生物大肠杆菌 K-12 转录调控和操纵子组织的主要注释项目。该项目是之前资助的概念延续和扩展，支持丰富 RegulonDB 的注释工作。除了持续的文献整理之外，我们建议对基因组中所有可能缺失的启动子位点进行详尽的映射，并对调控网络进行一些理论分析，以及与其他实验室进行的微阵列数据的模拟和比较。我们计划通过计算预测来补充文献知识，并积极寻找缺失的链接，使我们能够利用几个现有的数据库将转录、运输、信号转导和新陈代谢整合在一起。我们将确定这些细胞知识与多个实验室进行的大量微阵列实验的一致性。这些比较需要建立几个计算和化学模型，用于决定基因表达的调节简单和复杂相互作用，以及它们在整个细胞网络（运输、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来分析模块、基序和图谱中的网络。最后，我们打算对网络动态进行低分辨率离散模拟，并对所选地图和网络子组件进行详细的随机建模。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体调控网络的经典和主动注释的整体质量和深度。更好地了解整个细胞将为基础生物学做出重要贡献，从而为了解健康和疾病奠定基础。