Elucidation of Host and Bacterial Factors that Influence Resilience and Robustnes

影响弹性和鲁棒性的宿主和细菌因素的阐明

• 批准号: 8823468
• 负责人: Travis J Wiles
• 金额: $ 5.42万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8823468
• 关键词: Address; Aeromonas; Affect; Antibiotic Therapy; Antibiotics; Bacteria; Bacterial Genes; Biological Models; Candidate Disease Gene; Cataloging; Catalogs; Cells; Chromosome Mapping; Collection; Colon Carcinoma; Communities; Complex; Dexamethasone; Diabetes Mellitus; Disease; Engineering; Event; Exhibits; Extinction (Psychology); Genes; Genetic Screening; Genomics; Gnotobiotic; Goals; Health; Homeostasis; Human; Human body; Immune; Immune system; Immunosuppression; Immunosuppressive Agents; Individual; Inflammatory Bowel Diseases; Integration Host Factors; Intestines; Investigation; Larva; Libraries; Microbe; Molecular; Monitor; Nutrient; Obesity; Oxidants; Pattern; Pharmaceutical Preparations; Phylogenetic Analysis; Predisposition; Probiotics; Production; Property; Recovery; Research; Research Personnel; Resistance; Resources; Ribosomal RNA; Role; Systems Biology; Testing; Therapeutic; Therapeutic Intervention; Time; Work; Zebrafish; antimicrobial peptide; base; design; fortification; frontier; gut microbiota; human disease; insight; interest; killings; microbial community; microorganism; resilience; response

DESCRIPTION (provided by applicant): The microorganisms of the human intestinal tract-known as the 'microbiota'-represent a dynamic and diverse community made up of over 500 species and 100 trillion cells. Advancements in genomics over the last decade have greatly facilitated the characterization of this complex multi-species symbiont. It has been found that phylum-level compositional shifts in the microbiota, which can be induced by environmental, host and bacterial factors, correlate with and promote human disease. The next frontier in this research field is to understand how potentially deleterious shifts in the microbiota occur and how such shifts might be corrected to treat disease. Herein I describe a systems biology approach to identify molecular and cellular determinants of microbiota robustness (resistance to perturbation) and resilience (recovery from perturbation). The overarching hypothesis guiding my research plan is that both bacteria and host-derived properties contribute to the compositional integrity of the microbiota. To address this hypothesis, I will employ a gnotobiotic zebrafish host model system that is amenable to high-throughput and real time investigation of host-associated microbial community dynamics. AIM 1 of my proposal will identify bacterial genes within a natural zebrafish bacterial isolate required to resist the colonization of an invasive species. AIM 2 will address the consequences of temporary host immunosuppression on the diversity and function of the microbiota. And in AIM 3 I will investigate the role of specie extinction events, which can be a consequence of antibiotic use, on the composition and function of the microbiota. Observations made during this work will inform the design of more effective probiotic and therapeutic regimes for treating diseases associated with pathogenic alterations of the microbiota.

描述（由申请人提供）：人类肠道的微生物称为“微生物群” - 代表一个动态和多样化的社区，由500多种和100万亿个细胞组成。在过去的十年中，基因组学的进步极大地促进了这种复杂的多种物种共生体的表征。已经发现，微生物群中的门水平的成分转移可以由环境，宿主和细菌因素引起，与人类疾病相关并促进人类疾病。该研究领域的下一个领域是了解微生物群的潜在有害转变以及如何纠正这种转变以治疗疾病。本文我描述了一种系统生物学方法，以鉴定微生物核鲁棒性（抗扰动）和弹性（从扰动中恢复）的分子和细胞决定因素。基本的假设指导我的研究计划，是细菌和宿主衍生的特性都有助于微生物群的组成完整性。为了解决这一假设，我将采用一种齿状斑马鱼宿主模型系统，该模型可与宿主相关的微生物社区动力学进行高通量和实时研究。我的建议的目标1将在自然斑马鱼细菌分离株中鉴定细菌基因，以抵抗入侵物种的定殖。 AIM 2将解决临时宿主免疫抑制对微生物群多样性和功能的后果。在AIM 3中，我将研究Spece灭绝事件的作用，这可能是抗生素使用的结果，在微生物群的组成和功能上。在这项工作中进行的观察结果将为治疗与菌群致病性改变有关的疾病的更有效益生菌和治疗方案的设计提供信息。