Microbial Engineering to Control the Structure and Function of the Gut Microbiome.

控制肠道微生物组结构和功能的微生物工程。

• 批准号: 10677794
• 负责人: Mark Mimee
• 金额: $ 41万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-05 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10677794
• 关键词: Behavior; Biochemical Pathway; Breathing; Collection; Communities; Development; Disease; Ecosystem; Engineering; Environment; Genes; Genetic; Genetic Determinism; Genetic Engineering; Health; Human; Individual; Investigation; Link; Metabolic; Microbe; Modeling; Molecular; Mus; Phylogenetic Analysis; Physiology; Play; Program Description; Property; Research; Role; Structure; Techniques; design; genetic manipulation; gut bacteria; gut microbiome; human microbiota; microbial; microbial community; microbiome; microbiome research; microbiota; multiple omics; new technology; predictive modeling; programs; resilience; response; symbiont; synthetic biology; tool; trait

Microbial Engineering to Control the Structure and Function of the Gut Microbiome SUMMARY The human microbiota, the collection of microbes that live on and in the body, is fully integrated with human physiology and has been extensively implicated in health and disease. As with all microbial communities, the summation of environmental, interbacterial, and interkingdom interactions governs both the composition and function of the microbiota. To date, top-down approaches have been largely used to study microbiome function, using multi-omics techniques to draw correlations between microbial taxa, genes, and metabolites with functional properties in different environmental conditions. While these studies contribute a rich set of hypotheses, bottom-up approaches are required to causally pinpoint the molecular mechanisms through which microbes interact with their environment, one another, and the host. Synthesis of these mechanistic studies can further enable predictive models that can be leveraged to engineer microbiomes. Through the development and application of novel technologies, the research program described herein aims to predictively engineer ecological responses and metabolic functions in the gut microbiome. A defined microbial community that mirrors the phylogenetic and functional diversity of natural communities will be used as a testbed to model the emergent phenomena that arise as a result of interbacterial interactions. Using inspiration from natural microbial communities to fuel synthetic biology approaches, we will create new tools to allow for genetic manipulation and expression control in previously intractable gut symbionts. These genetic tools will be applied to link microbial genes and associated functions with emergent properties of microbial communities, including resilience to environment perturbations and metabolic networks in the mouse gut. These studies will provide an experimental framework to pursue investigations into the core functions that structure microbial communities and to establish design rules for rational microbiome engineering.

微生物工程控制肠道微生物群的结构和功能