NSF Postdoctoral Fellowship in Biology FY 2020:Consequences of reductive evolution on cell wall metabolism in the obligate intracellular bacterium Rickettsia parkeri

该行动为2020财年美国国家科学基金会生物学博士后研究奖学金提供资金，扩大生物学中代表性不足群体的参与。该奖学金支持研究员的一项研究和培训计划，该计划将增加生物学中代表性不足的群体的参与。细菌是单细胞微生物，它们已经进化到可以在各种自然环境中生存，包括土壤、湖泊，甚至海洋深处。一些细菌已经进化到依赖宿主，形成有益的（内共生）或有害的（致病）关联。立克次体是一种只在宿主细胞内生长的细菌，可以通过蜱虫和其他节肢动物传播给哺乳动物。通过进化，立克次体失去了许多支持基本活动的基因，导致它们严格依赖宿主生长。虽然对允许自由生物生长的过程的理解已经很发达，但由于缺乏工具，对生活在宿主细胞内的细菌的这些过程的了解有限。通过该奖项，该研究员将翻译可用于自由生物的技术，以了解居住在宿主细胞内的细菌如何生长和复制，重点研究立克次体的一种成员。该项目有可能影响昆虫生物学，并为下一代抗菌药物提供新的细菌或宿主靶点。此外，该项目将开发一个研究生和博士后实习生指导计划，称为BRIDGE，通过最大限度地提高研究生的晋升和保留来增强多样性。以立克次体为立克次体的代表成员，本项目的目标是：(1)实施活体和固定显微镜方法，定量评估寄主细胞内单个细菌细胞的生长情况；(2)表征慢生长突变体。为了实现这些目标，该研究员将开发实时延时和固定显微镜，用于活性细胞壁合成的探针与定量图像分析工具相结合。该方法将建立定量胞内细菌生长参数的方法。其次，研究人员将描述细胞壁循环途径因子AmpG中生长缓慢的突变体的细胞内生长和细胞壁代谢。在项目执行期间，研究员将接受赞助科学家和博士后咨询委员会的培训，并将利用约翰霍普金斯大学专业发展和职业办公室的资源。最后，该研究员将通过创建一个名为BRIDGE的指导项目，扩大代表性不足群体的参与。该计划的核心是将URM博士后作为导师与约翰霍普金斯大学多元化和包容性组织的研究生相匹配，以帮助研究生发展和实现他们的个人发展计划目标，同时推进博士后培训。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2020, Broadening Participation of Groups Under-represented in Biology. The fellowship supports a research and training plan for the Fellow that will increase the participation of groups underrepresented in biology. Bacteria are single-celled microbes that have evolved to colonize a wide variety of natural environments including soil, lakes, and even the depths of the ocean. Some bacteria have evolved to become dependent on hosts, forming beneficial (endosymbiotic) or detrimental (pathogenic) associations. The Rickettsiales are bacteria that grow exclusively inside a host cell and may be transmitted to mammals by ticks and other arthropods. Through evolution, the Rickettsiales have lost many genes that support essential activities, leading to their strict dependence on the host for growth. While the understanding of processes that allow growth of free-living organisms is well-developed, knowledge of these processes in bacteria that live within host cells is limited due to a lack of tools. Through this award, the fellow will translate technologies available for free-living organisms to understand how bacteria residing inside host cells grow and replicate, focusing on a member of the Rickettsiales. The project has the potential to impact insect biology and to provide novel bacterial or host targets for the next generation of antimicrobial drugs. In addition, the project will develop a graduate student and postdoctoral trainee mentoring program, called BRIDGE, to enhance diversity by maximizing graduate student advancement and retention. Using Rickettsia parkeri as a representative member of the Rickettsiales, the objectives of this project are (1) to implement live and fixed microscopy methods for quantitatively evaluating growth of single bacterial cells within the host cell and (2) to characterize R. parkeri slow-growing mutants. To address these objectives, the fellow will develop live time-lapse and fixed microscopy with probes for active cell wall synthesis coupled to quantitative image analysis tools. This approach will establish methods for quantifying parameters of growth in intracellular bacteria. Second, the fellow will characterize intracellular growth and cell wall metabolism of slow-growing mutants in the cell wall recycling pathway factor AmpG. During execution of this project, the fellow will receive training by the sponsor scientist and a postdoctoral advisory committee, and will leverage resources available at the Professional Development and Career Office at Johns Hopkins University. Finally, the fellow will broaden the participation of underrepresented groups by creating a mentoring program called BRIDGE. The core of the program involves matching URM postdocs as mentors to graduate students from diversity and inclusion-oriented organizations at Johns Hopkins University to help graduate students develop and meet their individual development plan goals while advancing postdoctoral training.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.