Characterizing Natural Product Mediated Microbial Interactions

表征天然产物介导的微生物相互作用

• 批准号: 9764392
• 负责人: Vanessa V Phelan
• 金额: $ 38.54万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9764392
• 关键词: Affect; Biochemical; Chemicals; Communities; Complex; Data; Disease; Genetic; Goals; Health; Human; Mass Spectrum Analysis; Mediating; Metabolic; Methods; Microbe; Modernization; Molecular; Natural Products; Output; Research; Role; Shapes; Signal Transduction; Structure; Work; base; cystic fibrosis patients; insight; lung microbiota; member; microbial; microbial community; microbiome; microbiota; microorganism interaction; network models; pressure; small molecule

Project Summary/Abstract Humans each harbor a complex microbiome with the genetic potential to produce a vast array of natural products. Recent sequencing data suggests that these microbiome communities are critical for maintaining our health. Shifts in microbiome communities have been correlated to a number of diseases, yet we know remarkably little about the role of natural products in maintaining these communities. My group’s long-term goal is to define metabolite mediated relationships between members of the pulmonary microbiota of cystic fibrosis patients and elucidate their functional role in community dynamics. We hypothesize that the constituents of the microbiome interact using natural products and that a convergence of these chemical signals determines community structure. The overall objective of this proposal is to develop and apply modern mass spectrometry based workflows in combination with traditional and emerging chemical, molecular, and biochemical approaches to investigate the role of small molecules within microbiome communities. Over the next five years, we will chemically characterize understudied microbes, 2) elucidate how microbial community structure affects metabolic output, and 3) understand how exogenous pressures (i.e. treatment, host metabolites, etc.) shape microbiome structure and function. This information will then be incorporated into a model network of microbiome interactions. The propose research is significant because it will provide the research community with a fundamental understanding of how microbiome derived compounds impact the structure and function of the microbiome, especially in regards to treatment. While our work focuses on the CF pulmonary microbiota, the methods and approaches we develop are broadly applicable to any microbiome.

项目总结/摘要 每个人都拥有一个复杂的微生物组，具有产生大量天然产物的遗传潜力。 最近的测序数据表明，这些微生物群落对维持我们的健康至关重要。 微生物群落的变化与许多疾病有关，但我们所知甚少 关于天然产品在维持这些社区中的作用。我的团队的长期目标是 代谢物介导的囊性纤维化患者的肺微生物群成员之间的关系， 阐明其在社区动态中的功能作用。我们假设微生物组的组成 这些化学信号的汇聚决定了群落的形成， 结构本提案的总体目标是开发和应用基于 结合传统和新兴的化学、分子和生物化学方法， 研究小分子在微生物群落中的作用。未来五年，我们将 化学表征未研究的微生物，2）阐明微生物群落结构如何影响 代谢输出，以及3）了解外源性压力（即治疗、宿主代谢物等）形状 微生物的结构和功能然后，这些信息将被纳入微生物组的模型网络中 交互.这项研究的意义重大，因为它将为研究界提供一个 基本了解微生物组衍生化合物如何影响微生物的结构和功能， 微生物组，特别是在治疗方面。虽然我们的工作集中在CF肺微生物群， 我们开发的方法和途径广泛适用于任何微生物组。