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: 8005237
• 负责人: William Harcombe
• 金额: $ 4.76万
• 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/8005237
• 关键词: Architecture; Bacteria; Behavior; Biochemical; Biochemical Pathway; Biochemistry; Biological Models; Biology; Cell physiology; Cells; Communities; Complex; Computer Simulation; Development; Disease; 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(申请人提供)：微生物群落通过引起疾病、抵御病原体和控制新陈代谢，极大地影响人类健康。因此，了解塑造微生物群落的内容和动态的力量是非常有意义的。这样的理解将需要一种综合的方法，将微生物新陈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式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生长所需的代谢物后，在两个物种的群落中观察到生产力提高。进化前后细菌的代谢、转录和基因组分析将被用来确定观察到的进化变化的功能原因。第二个目标是确定在两个物种群落中观察到的进化模式可以在多大程度上外推到更复杂的群落。甲烷杆菌将与大肠杆菌和沙门氏菌一起生长，以创造一个所有三个物种都需要生长的群落。关于合作进化的理论是否仍然能够预测在这种更复杂的组合中的适应，将受到考验。此外，还将使用高吞吐量方法来测试社区演化的并行程度。第三个目标是测试一种细菌进化成另一种细菌时对代谢物的限制。一种新的通量平衡分析的实现将被用来确定沙门氏菌可以进化来补偿的完整的一套大肠杆菌基因功能。这些预测将通过在10个具有代表性的大肠杆菌基因敲除株存在的情况下进化的沙门氏菌来验证。 公共卫生相关性：微生物群落极大地影响人类健康。它们让我们生病，保护我们远离疾病，并决定我们如何代谢我们吃的东西。因此，了解塑造微生物群落的内容和动态的力量是非常有意义的。这项研究调查了进化如何改变细菌群落的性质。