Comparative Community Genomics of the Gut Microbiota

肠道微生物群的比较群落基因组学

• 批准号: 7017133
• 负责人: MARIA Pilar FRANCINO
• 金额: $ 25.15万
• 依托单位: UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7017133
• 关键词: adult human (21+); artificial chromosomes; bacteria infection mechanism; bacterial DNA; bacterial genetics; biotechnology; breast feeding; clinical research; drug resistance; enteric bacteria; feces; functional /structural genomics; genetic library; genetic screening; genome; host organism interaction; human subject; infant animal; infant human (0-1 year); laboratory mouse; mature animal; nucleic acid sequence; parents; population genetics; symbiosis

DESCRIPTION (provided by applicant): The global aim of this project is to increase our understanding of the diverse microbial community that inhabits the human gastrointestinal (GI) tract. This microbiota plays essential roles in human health, including a significant contribution to the digestive process, promotion of gut maturation and integrity and modulation of the immune system. Moreover, the microbiota interacts with pathogenic agents in several complex ways. On one hand, resident bacteria exert a protective barrier effect against enteropathogens; but, on the other, they could contribute to enrich the arsenal of incoming pathogens through horizontal transmission of genes involved in host-microbe interaction or antibiotic resistance. In addition, many normally benign GI commensals have the potential to become opportunistic pathogens in compromised hosts. Elucidating the composition and coding capabilities of the GI microbiota is therefore crucial for a comprehensive analysis of infectious disease. To advance towards this goal, we will produce large-insert bacterial artificial chromosome (BAC) libraries from genomic DNA isolated directly from fecal samples. The availability of BAC libraries will allow for a deep characterization of the GI microbiota by providing extensive genomic sequences that will serve to elucidate the coding capabilities as well as the phylogenetic positions of the members of this community. Given that the composition of the GI microbiota varies greatly with age and diet, we have chosen to generate BAC libraries from two very distinct stages of microbiota development: adults and breast-feeding infants, as represented by mother and child. Because of the widespread use of mice as an experimental system to study both infectious diseases in general and the GI microbiota in particular, we will also generate BAC libraries for mouse mother and suckling pup. To maximize our insight into the evolution and ecology of infectious disease, we will focus our sequencing efforts towards genomic regions relevant to pathogenicity and other ecological interactions, both among the microbial community members and between microbes and host.

描述（由申请人提供）： 该项目的全球目的是提高我们对居住在人类胃肠道（GI）区域的各种微生物社区的理解。这种微生物群在人类健康中起着重要作用，包括对消化过程的重要贡献，促进肠道成熟和完整性以及免疫系统的调节。此外，微生物群以几种复杂的方式与致病剂相互作用。一方面，居民细菌对肠道病的保护产生了保护性的屏障作用。但是，另一方面，它们可以通过涉及宿主 - 微生物相互作用或抗生素耐药性的基因的水平传播来富集传入病原体的武器库。此外，许多通常的良性GI共同体有可能成为受损宿主的机会性病原体。因此，阐明胃肠道菌群的组成和编码能力对于对传染病的全面分析至关重要。 为了迈向这一目标，我们将从直接从粪便样品中分离出的基因组DNA中生产大型插入细菌人造染色体（BAC）文库。 BAC文库的可用性将通过提供广泛的基因组序列来深入胃肠道菌群，以阐明该社区成员的编码能力以及系统发育位置。鉴于胃肠道菌群的组成随着年龄和饮食而变化很大，我们选择从微生物群发育的两个非常不同的阶段产生BAC文库：成人和母乳喂养的婴儿，由母亲和儿童代表。由于小鼠作为实验系统的广泛使用，尤其是研究传染病，尤其是胃肠道疾病，我们还将为小鼠母亲和哺乳幼犬生成BAC库。为了最大程度地了解传染病的进化和生态学，我们将在微生物社区成员以及微生物和宿主之间将测序努力集中在与致病性和其他生态相互作用有关的基因组区域。