Microbial Community Dynamics: A Systems Biology and Evolutionary Approach

微生物群落动力学：系统生物学和进化方法

• 批准号: 8217311
• 负责人: William Harcombe
• 金额: $ 5.13万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8217311
• 关键词: Architecture; Bacteria; Behavior; Biochemical; Biochemical Pathway; Biochemistry; Biological Models; Biology; Cell physiology; Cells; Communities; Complex; Computer Simulation; Development; Disease; Drug Delivery Systems; Eating; Ecology; Engineering; Environment; Equilibrium; Escherichia coli; Evolution; Food; Foundations; Genetic; Genomics; Growth; Health; Human; Investigation; Knock-out; Large-Scale Sequencing; Link; Metabolic; Metabolic Pathway; Metabolism; Metagenomics; Methods; Methylobacterium extorquens; Microbe; Modeling; Nature; Nutrient; Pattern; Pharmaceutical Preparations; Pharmacologic Substance; Physiology; Play; Population Dynamics; Process; Production; Productivity; Property; Resources; Role; Salmonella; Salmonella enterica; Shapes; Skin; System; Systems Biology; Techniques; Testing; Vagina; Work; base; biochemical model; driving force; enzyme mechanism; experience; gene delivery system; gene function; insight; interest; metabolomics; microbial; microbial community; novel; pathogen; public health relevance; research study; theories; tool; trait; transcriptomics

DESCRIPTION (provided by applicant): Microbial communities dramatically influence human health through causing disease, protecting against pathogens, and manipulating metabolism. It is therefore of great interest to understand the forces that shape the content and dynamics of microbial communities. Such an understanding will require an integrated approach that ties the biochemistry of microbial metabolism to ecological and evolutionary processes. The first aim is to utilize systems biology tools to determine the functional basis of the cooperation that evolved in a model microbial community. Increased productivity was observed in a two-species community after Salmonella enterica evolved to secrete a metabolite necessary for the growth of the Escherichia coli. Metabolomic, transcriptomic and genomic analysis of the bacteria before and after evolution will be used to determine the functional cause of the observed evolutionary change. The second aim is to determine the extent to which evolutionary patterns observed in two-species communities can be extrapolated to more complex communities. Methylobacterium extorquens will be grown with E. coli and Salmonella to create a community in which all three species are required for growth. It will be tested whether theory about the evolution of cooperation can still predict adaptation in this more complex assemblage. Additionally, high throughput methods will be used to test the degree to which community evolution is parallel. The third aim is to test the constraints on the metabolites one bacteria will evolve to provide another. A novel implementation of flux balance analysis will be used to determine the complete set of E. coli gene functions for which Salmonella can evolve to compensate. These predictions will be tested by evolving Salmonella in the presence of 10 representative E. coli knockout lines. PUBLIC HEALTH RELEVANCE: Microbial communities dramatically influence human health. They make us sick, protect us from illness and determine how we metabolize the things we eat. It is therefore of great interest to understand the forces that shape the content and dynamics of microbial communities. This study investigates how evolution changes the properties of communities of bacteria.

描述（由申请人提供）：微生物群落通过引起疾病、抵御病原体和操纵代谢来显著影响人类健康。因此，了解塑造微生物群落的内容和动态的力量是非常有趣的。这样的理解将需要一种综合的方法，将微生物代谢的生物化学与生态和进化过程联系起来。 第一个目标是利用系统生物学工具来确定在模型微生物群落中进化的合作的功能基础。在肠道沙门氏菌进化为分泌大肠杆菌生长所必需的代谢产物后，在两种群落中观察到生产力增加。将使用进化前后细菌的代谢组学、转录组学和基因组学分析来确定所观察到的进化变化的功能原因。 第二个目标是确定在何种程度上观察到的进化模式在两个物种的社区可以外推到更复杂的社区。扭脱甲基杆菌将与E.大肠杆菌和沙门氏菌创造一个社区，其中所有三个物种都需要生长。关于合作进化的理论是否仍然能够预测这种更复杂的组合中的适应，这将得到检验。此外，高通量方法将用于测试社区进化的并行程度。 第三个目标是测试一种细菌进化为另一种细菌提供代谢物的限制。一种新的实现磁通平衡分析将被用来确定完整的E。大肠杆菌基因的功能，沙门氏菌可以进化来弥补。这些预测将通过在10个代表性的E. coli敲除株系。 公共卫生相关性：微生物群落极大地影响人类健康。它们使我们生病，保护我们免受疾病的侵害，并决定我们如何代谢我们所吃的东西。因此，了解塑造微生物群落的内容和动态的力量是非常有趣的。这项研究调查了进化如何改变细菌群落的特性。