Regulation and Function of a Mutualistic Bacterial Host Range Specificity Determinant

所有植物和动物宿主都与微生物共生体相关联，这些共生体可以促进健康或引起疾病。许多微生物-宿主关系（有益的和致病的）是特异性的;只有一个微生物物种或菌株与一个宿主或组织密切相关。一个基本但尚未回答的生物学问题是，是什么允许某些微生物而不是其他微生物在特定宿主或组织中定居。这项研究调查了细菌和动物共生伙伴如何识别彼此，同时排除不需要的物种。正在研究的细菌定植在一种小型土壤蛔虫（线虫）的肠道中，并表达出对线虫有益的特性。该项目的重点是细菌膜蛋白，这是必要的殖民和决定特定的线虫物种的特异性。这种蛋白质代表了存在于定殖动物粘膜的许多共生体中的蛋白质家族。遗传，生物化学，物理和显微镜方法将用于揭示蛋白质的结构，生化功能和相互作用的宿主因子。总的来说，这项工作将加速研究一类未充分研究的膜蛋白的技术进步。此外，这项研究将提供范式，对动物微生物定植的分子基础产生广泛的见解，以及什么可能使微生物超出其当前的定植范围并进入新的宿主或组织部位。公众将通过社区研讨会和高中外展计划了解这项研究。 该项目包括国家科学基金会建议的本科教育的五个核心概念，并将用于生成一个综合课程，强调这些领域。本科生，研究生和博士后学徒将通过直接的科学探究在结构生物学，分子生物学，线虫学和细菌学领域进行培训。 因此，该项目将提供细菌与动物宿主相互作用的基础知识，并将有助于培养未来的科学家，以进一步应用这些知识。

All plant and animal hosts associate with microbial symbionts that can contribute to health or cause disease. Many microbe-host associations (both beneficial and pathogenic) are specific; only a single species or strain of microbe exists in close association with a single host or tissue. A fundamental but unanswered biological question is what allows some microbes but not others to colonize specific hosts or tissues. This research investigates how bacteria and animal symbiotic partners recognize each other while excluding unwanted species. The bacterium being studied colonizes the intestine of a small soil-dwelling roundworm (nematode) , and expresses traits beneficial for the nematode. The project focuses on a bacterial membrane protein that is necessary for colonization and dictates specificity for certain nematode species. This protein represents a family of proteins present in many symbionts that colonize animal mucosae. Genetic, biochemical, physical, and microscopy approaches will be used to reveal the structure, biochemical function, and interacting host factors of the protein. In general, the work will hasten technical advances for investigating an understudied class of membrane proteins. Also, the research will provide paradigms that yield broad insights into the molecular basis of microbial colonization of animals and what might allow microbes to expand beyond their current colonization ranges and enter new hosts or tissue sites. The public will be exposed to this research through community seminars and high school outreach programs. The project encompasses the NSF-recommended five core concepts for undergraduate education, and will be used to generate an integrated curriculum emphasizing these areas. Undergraduate, graduate, and post-doctoral apprentices will be trained in the areas of structural biology, molecular biology, nematology, and bacteriology through direct scientific inquiry. Thus, this project will provide fundamental knowledge of bacterial interactions with animal hosts, and will help train future scientists with expertise to further apply this knowledge.