权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Contact-dependent interbacterial responses modulate intestinal colonization by Bacteroides species

接触依赖性细菌间反应调节拟杆菌属的肠道定植

基本信息

批准号：
10636949
负责人：
Dustin E Bosch
金额：
$ 16.15万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-18 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10636949
关键词：
Affect Anatomy Applications Grants Bacteria Bacteriology Bacteroides Bacteroides fragilis Bacteroides thetaiotaomicron Bacteroidetes Board Certification Carbohydrates Cells Clinical Clinical Pathology Coculture Techniques Communication Communities Complex DNA Development Development Plans Diet Disease Doctor of Medicine Doctor of Philosophy Ecosystem Educational workshop Elements Environment Faculty Funding Genome Germ-Free Gnotobiotic Goals Grant Growth Human Immunity Individual Intestines K-Series Research Career Programs Lateral Leadership Link Mannans Mediating Mentored Clinical Scientist Development Award (K08)Mentorship Microbiology Molecular Mus Pathology Physicians Polysaccharides Process Proteins Proteomics Research Research Infrastructure Research Personnel Resource Development Role Scientist Shapes Starch Structural Protein System Technology Testing Therapeutic Toxin Training Translating Transmembrane Transport United States National Institutes of Health Writing Yeasts antagonist bacterial genetics career career development cell behavior experimental study gastrointestinal gut colonization gut microbiota human disease meetings microbiota mouse model novel nuclease professor response skills symbiont targeted treatment

项目摘要

Project Summary/Abstract The diverse group Bacteroidales is a predominant component of human intestinal microbiota, linked to numerous disease processes. Manipulation of Bacteroidales at the genus and species level holds therapeutic potential, but requires a more detailed understanding of the intestinal ecosystem. Bacteroides spp. genomes encode polysaccharide utilization loci (PUL), allowing enzymatic breakdown, membrane transport, and utilization of complex carbohydrates. Bacteroides spp. antagonize one another within the intestinal environment by delivering toxic effectors via contact-dependent type VI secretion systems (T6SS), resulting in altered capacities for colonization and persistence. The central hypothesis of this proposal is that contact among Bacteroides spp. results in dynamic adaptive responses that alter cellular behavior and contribute to persistence in the intestinal environment. The proposed experiments will discover contact-dependent proteomic responses important for competition within Bacteroides communities using cutting-edge proteomics technology (Aim 1). Molecular mechanisms of two known contact-dependent responses, altered polysaccharide utilization (Aim 2) and T6SS- mediated delivery of hcp-effector fusions (Aim 3), will be elucidated and translated to competitive growth and intestinal colonization in a gnotobiotic mouse model. A long-term research goal is to understand mechanisms underlying interbacterial interactions among intestinal symbionts for the development of targeted therapeutics. The candidate for this career development award is an M.D./Ph.D. physician scientist with board certification in anatomic and clinical pathology. The research proposed in this grant application will be conducted under the mentorship of Dr. Joseph Mougous, Professor of Microbiology, and Dr. Matthew Yeh, Professor of Pathology. The candidate will join faculty in a department with ample clinical resources for development of specialized expertise in gastrointestinal pathology, established NIH-funded investigators and research infrastructure, and a track record of strong support for physician scientists. The candidate is committed to a career as a physician scientist and seeks further scientific training. Career development plans include participation in relevant local and national meetings, advanced didactics and workshops to gain expertise in commensal bacteriology, build research communication and grant writing skills, and develop leadership and management skills. This mentored clinical scientist development award will facilitate the candidate’s transition to become a competitive NIH-funded independent investigator.

项目摘要/摘要不同的类杆菌是人类肠道微生物区系的主要组成部分，与许多疾病过程。在属和种水平上操纵类杆菌具有治疗潜力，但需要对肠道生态系统有更详细的了解。拟杆菌属基因组编码多糖利用位点(PUL)，允许酶的分解、膜的运输和利用复杂的碳水化合物。拟杆菌属在肠道环境中通过传递通过接触依赖型VI型分泌系统(T6SS)产生的毒性效应器，导致对殖民主义和坚持不懈。这一建议的中心假设是类杆菌属之间的接触。导致动态适应性反应，从而改变细胞行为并有助于肠道内的持久性环境。拟议中的实验将发现接触依赖的蛋白质组反应对使用尖端蛋白质组学技术的类杆菌群落内的竞争(目标1)。分子两种已知的接触依赖性反应的机制，改变多糖利用(AIM 2)和T6SS- HCP-效应器融合的介导性传递(目标3)将被阐明并转化为竞争性增长和诺生菌小鼠模型中的肠道定植。一个长期的研究目标是了解机制肠道共生菌之间潜在的细菌间相互作用，用于靶向治疗的开发。这一职业发展奖的候选人是医学博士/博士内科科学家，拥有解剖和临床病理学。这项拨款申请建议的研究将在微生物学教授Joseph Mougous和病理学教授Matthew Yeh博士的指导。应聘者将进入一个拥有充足临床资源的院系，以发展专科胃肠道病理学方面的专业知识，NIH资助的现有调查人员和研究基础设施，以及对内科科学家给予大力支持的记录。这位候选人致力于内科医生的事业并寻求进一步的科学培训。职业发展计划包括参与相关的本地以及国家会议、高级教学和讲习班，以获得共生细菌学方面的专业知识，建立研究沟通和授予写作技能，并培养领导和管理技能。这位导师临床科学家发展奖将促进候选人转变为具有竞争力的NIH资助的独立调查员。