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Carbohydrate Public Good Interactions in Healthy and Dysbiotic Bacteroidales Communities

健康和失调拟杆菌社区中的碳水化合物公共利益相互作用

基本信息

批准号：
9420523
负责人：
Seth Rakoff-Nahoum
金额：
$ 19.2万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-02-02 至 2022-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9420523
关键词：
Adult Affect Anaerobic Bacteria Bacteria Bioinformatics Biology Biopsy Carbohydrates Childhood Communicable Diseases Communities Computer Analysis Development Development Plans Diet Dietary Polysaccharide Digestion Disease Dissection Ecology Energy-Generating Resources Enzymes Food Funding Generations Genes Genetic Gnotobiotic Goals Gram-Negative Bacteria Health Health Promotion Home environment Hospitals Human Human body Hydrolase Immunology In Vitro Individual Inflammation Inflammatory Bowel Diseases Intestines Knowledge Mediating Membrane Mentors Mentorship Microbe Modeling Molecular Mucous Membrane Mus Pathogenicity Phenotype Physicians Physiological Planet Earth Plants Play Polysaccharides Research Research Personnel Research Project Grants Research Proposals Research Training Resources Role Scientist Secure Series Shapes Source Structure System Testing Therapeutic Intervention Variant Vesicle Woman Work bacterial genetics base career career development community intervention dysbiosis experimental study genetic approach gut microbiota in vivo interdisciplinary approach medical schools member microbial microbiota microorganism mouse model mutant next generation next generation sequencing novel skills social

项目摘要

This proposal describes a 5-year career mentored research project with the goal of defining the role of cooperative and selfish utilization of dietary- and host- derived carbohydrates by the Bacteroidales in the ecological interactions and composition of the gut microbiota. Successful completion of the research and training plan will enable the investigator to gain the skills necessary to secure independent funding and transition into an independent physician- scientist with the long term goals of exploring the human gut microbiota through multidisciplinary approaches. The research aims and career development plan will work towards mastery and independence in bacterial genetics approaches to gut anaerobic bacteria and proficiency in both eco-evolutionary and bioinformatic/computational analysis of the microbiota. The primary co- mentors are Dr. Laurie Comstock – a world expert in the bacterial genetics of the Bacteroidales and Dr. Matthew Waldor – a leader in next-generational sequencing approaches to bacteria, both at the Brigham and Women's Hospital/Harvard Medical School. The collaborative and mentorship team is comprised of a local, multi-institutional group of experts in infectious diseases, theoretical ecology and modeling, microbial ecology, evolutionary biology, mucosal immunology and inflammatory bowel disease. The research proposal seeks to explore ecological interactions among the Bacteroidales, the predominant Gram negative bacteria of the human gut, which have important impacts on host health and disease. Our preliminary findings suggest that the Bacteroidales use diverse strategies to survive on dietary polysaccharides based on variation in the digestion of these carbohydrates and liberation and utilization of these digested products as public goods. We hypothesize that carbohydrate public good based interactions centered on the Bacteroidales are fundamental determinants of the composition and dynamics of individuals and microbiota communities. In this proposal we will use high throughput in vitro phenotypic analysis to assign ecotypes to members of co-resident healthy and dysbiotic Bacteroidales natural communities, use bacterial genetics to identify the genes involved in key carbohydrate-based interactions, and determine the impact of selfish and public goods-based carbohydrate interactions on the composition and dynamics of the gut microbiota in vivo. Collectively these proposed studies seek to provide critical information on the ecological determinants of naturally human Bacteroidales communities and will be important for our understanding of the microbiota and attempts to shape this community in health and disease.

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