RUI: Aggregation and Colonization Mediated by Bacterial Surface Factors

智力优势细菌可以在多细胞生物体中定居，作为复杂群落的一部分生活在宿主体内或宿主表面。 它们利用特定的表面蛋白质相互粘附，并粘附在宿主细胞上，形成一个稳定的细菌群落，不会被冲走。 在这项研究中，指导的本科生将识别和表征蛋白质定植因素，并确定它们如何相互作用。 Hra 1以前被描述为外表面蛋白的凝集素家族的成员，其通过自缔合介导相邻的细菌细胞彼此粘附。 Hra 1还介导大肠杆菌与真核细胞的体内结合，并特异性地促进线虫肠道的小聚集体定殖。 有初步证据表明，第二种蛋白质Aap可以阻止Hra 1介导的相互作用。 Aap的抑制活性提供了一种机制，用于限制Hra 1介导的协会，因为细菌向其肠道生态位移动。 然而，一旦细菌到达合适的生态位，Aap必须被移除以进行定植。 这项研究将确定Aap去除的机制，从而确定Hra 1和Aap如何共同工作，以确保细菌能够以优化线虫肠道定植的方式结合和分散。 该项目还将确定参与肠道定植的新表面因子，并确定它们如何与已知的表面蛋白相互作用。 除了识别参与相同细菌之间结合的蛋白质外，该项目还将专注于发现允许不同种类细菌相互作用的表面蛋白质，作为了解生活在单个多细胞生物体内的多种细菌之间的社区组织的第一步。 细菌是地球上最丰富的生命形式，通过尚不清楚的机制在各种各样的生物和非生物小生境中定居。该项目将提高目前对细菌群落如何在其他生物体内建立和持续存在的理解，并增加对细菌表面蛋白结构和功能的了解。 解决与该项目相关的问题所需的研究将主要由在哈弗福德学院工作的本科生进行，并由在那里任教的首席研究员监督。 该项目将为这些学生提供早期机会，希望提高他们对科学的兴趣和保留。 每年将有4至8名学生，包括妇女和其他在科学领域代表性不足的群体，参与实验室研究项目。 其他几十名学生将通过主要研究者开发和教授的课程中的课程模块和课堂示例来丰富。 这包括20-40名学生，他们每年将参加基于探究的实验室研究课程，这将使他们接触微生物学，分子生物学和计算科学的技能。

Intellectual MeritBacteria that can colonize multi-cellular organisms live in or on their hosts as part of complex communities. They use specific surface proteins to adhere to one another, and to host cells, to form a stable community of bacteria that are not washed away. In this research, mentored undergraduate students, will identify and characterize protein colonization factors and determine how they interact with one another. Hra1 was previously described as a member of the agglutinin family of outer surface proteins which by self-association mediates adjacent bacterial cells to adhere to one another. Hra1 also mediates in vivo binding of Escherichia coli to eukaryotic cells and specifically promotes colonization of nematode worm intestines in small aggregates. There is preliminary evidence that suggests that a second protein, Aap, prevents Hra1 mediated interactions. The inhibitory activity of Aap provides a mechanism for restricting Hra1 mediated associations as bacteria travel towards their intestinal niche. Once bacteria reach a suitable niche however, Aap must be removed for colonization to ensue. This research, will determine the mechanism for Aap removal and thus how Hra1 and Aap work together to ensure that bacteria can bind and disperse in a manner that optimizes colonization of nematode intestines. The project will also identify new surface factors involved in intestinal colonization and determine how, if at all, they interact with known surface proteins. In addition to identifying proteins involved in binding among identical bacteria, the project will focus on uncovering surface proteins that allow different species of bacteria to interact with one another, as a first step to understanding community organization among the many types of bacteria living within a single multi-cellular organism. Broader Impact Bacteria are the most abundant life-forms on earth and colonize a wide variety of living and non-living niches by mechanisms that are not very well understood. This project will improve current understanding of how communities of bacteria are established and persist within other organisms, as well as add to knowledge on the structure and function of bacterial surface proteins. The research required to address questions relevant to this project will largely be performed by undergraduate students working at Haverford College and overseen by a principal investigator, who teaches there. The project will provide early opportunities for such students with the hope of increasing their interest and retention in science. Four to eight students, including women and other groups underrepresented in the sciences will be engaged in laboratory research projects each year. Several dozen other students will be enriched by course modules and classroom examples in courses that are developed and taught by the principal investigator. This includes 20-40 students who will participate in inquiry-based laboratory research courses each year that will expose them to skills in microbiology, molecular biology and computational science.