Genome-Scale in silico Model for E. coli

大肠杆菌基因组规模计算机模型

• 批准号: 7997484
• 负责人: BERNHARD O PALSSON
• 金额: $ 15.44万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-22 至 2010-12-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7997484
• 关键词: Algorithms; Bacteria; Behavior; Biochemical; Biochemical Pathway; Biological; Biological Process; Bioterrorism; Cells; Communities; Computer Simulation; Data; Development; Escherichia coli; Foundations; Gene Expression Regulation; Generations; Genes; Genetic Transcription; Genome; Genomics; Growth; Housing; Human; Internet; Knock-out; Knowledge; Laboratory Study; Messenger RNA; Metabolic; Metabolism; Methods; Microbe; Modeling; Open Reading Frames; Organism; Phenotype; Physiological; Procedures; Process; Prokaryotic Cells; Property; Protein Biosynthesis; Publishing; Reaction; Recording of previous events; Regulation; Research; Research Personnel; Research Project Grants; Science; Signal Transduction; Systems Analysis; Systems Biology; Technology; Transcriptional Regulation; Translation Process; Translations; Update; Work; design; mathematical model; novel; pathogen; programs; prospective; reconstruction; research study

DESCRIPTION (provided by applicant): Background: Established in 1998, this R01 program has led the development of genome-scale reconstructions of bacterial metabolism, with special emphasis on E. coli. These reconstructions have been disseminated to the research community at large and led to the generation of many scientific studies from laboratories around the world. These genome-scale metabolic reconstructions are turning out to be a common denominator in the study of systems biology in microbes. Proposed Program: This continuation proposal outlines a program with two specific aims. The first aim is to continue to develop reconstruction technologies and expand the scope of the networks currently being reconstructed to include, on a genome-scale, metabolism, regulation of gene expression, including two- component signaling, as well as transcription and translation. The fulfillment of this aim will result in the largest and most comprehensive network reconstruction for any organism. The second aim is to use the metabolic reconstruction, which now comprehensively represents known metabolism in E. coli, for prospective discovery of new metabolic capabilities in E. coli. Such discovery is accomplished through a gap filling procedure that follows high-throughput phenotyping experiments of wild-type and knock-out strains. This second aim is novel and represents fulfillment of the promise of systems biology to systematically discover new biological functions through integrative computational and experimental studies. General Impact: This program, if renewed, will continue to pioneer the new genome-scale science of prokaryotic cells. It will lay the foundation for similar analysis of human pathogens, environmentally important organisms and those of bioterrorism importance. The results will thus have an impact on both basic and applied studies of bacteria.

描述（由申请人提供）：背景：该R01计划于1998年成立，领导了基因组规模的细菌代谢重建，并特别强调了大肠杆菌。这些重建已被传播到整个研究界，并导致了世界各地实验室的许多科学研究。这些基因组规模的代谢重建是在微生物中系统生物学研究中的共同点。拟议计划：该延续提案概述了一个具有两个特定目标的计划。第一个目的是继续开发重建技术，并扩大当前正在重建的网络的范围，以包括基因组规模，代谢，基因表达的调节，包括两个成分信号，以及转录和翻译。实现这一目标将导致任何生物体最大，最全面的网络重建。第二个目的是使用代谢重建，现在全面代表大肠杆菌中已知的代谢，以预期发现大肠杆菌的新代谢能力。这种发现是通过差距填充程序来完成的，该过程遵循野生型和敲除菌株的高通量表型实验。第二个目标是新颖的，代表了系统生物学的承诺，可以通过综合计算和实验研究系统地发现新的生物学功能。一般影响：该程序，如果续签，将继续开拓新的原核生物基因组规模科学。它将为对人类病原体，环境重要的生物和生物恐怖重要性的类似分析奠定基础。因此，结果将对细菌的基本和应用研究产生影响。