NSF Postdoctoral Fellowship in Biology: Molecular Evolution of Bacterial Iron Piracy in Amoeba Hosts

美国国家科学基金会生物学博士后奖学金：阿米巴宿主细菌铁盗版的分子进化

• 批准号: 2208971
• 负责人: Edward Culbertson
• 金额: $ 13.8万
• 依托单位: Culbertson, Edward McLouth
• 依托单位国家: 美国
• 项目类别: Fellowship Award
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2208971&HistoricalAwards=false
• 关键词: NSF; Postdoctoral; Fellowship; Biology; Molecular

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2022, Integrative Research Investigating the Rules of Life Governing Interactions Between Genomes, Environment and Phenotypes. The fellowship supports research and training of the Fellow that will contribute to the area of Rules of Life in innovative ways. Environmental microorganisms, like bacteria, can evolve the molecular machinery to become disease pathogens in animal or human hosts. How does this occur? One hypothesis is that the need to survive predation by microeukaryotes, such as amoeba, selects for the evolution of genes that fight eukaryotic immunity. However, one ancient eukaryotic immune response is to deny pathogens access to iron. Successful pathogens have evolved tools to fight against the host to acquire iron. The outcome of this molecular tug of war is critical as iron is a vital micronutrient, required by most organisms for growth and survival. This project focuses on how adaptation to predatory amoeba, specifically the host-pathogen battle for iron has caused the bacterial pathogen Legionella pneumophila to evolve at the molecular level. The Fellow will recruit and mentor students in research in collaboration with the University of Pittsburgh. Host-pathogen conflicts can lead to molecular arms races, where domains of the proteins at the host-pathogen interface are subjected to ongoing cycles of rapid host and pathogen evolution. This project will test the hypothesis that the battle for iron has led iron sequestration genes to rapidly evolve as part of a molecular arms race between Legionella and its natural amoeba hosts. This project takes advantage of the power and utility of the Legionella/Dictyostelium infection model. Specifically, the Fellow will interrogate the evolution of MavN, a protein secreted by Legionella that functions to transport iron from the host cytosol into the Legionella-containing vacuole. The MavN protein shows signatures of rapid evolution and this sequence diversity has phenotypic consequences. These features suggest that MavN might be evolving due to a molecular arms race. This work bridges the current divide between evolutionary microbiology, bioinformatics, and bacteriology, and will enable the Fellow to enhance and develop skills that they will need to establish their own career as an independent researcher. This project will enable the Fellow to gain training in mentoring, scientific rigor, and how to foster inclusive environments in STEM. In addition, the Fellow will engage in efforts designed to increase scientific outreach in the Pittsburgh area by enhancing K-12 STEM curriculum.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.

该行动资助了2022财年的NSF生物学博士后研究奖学金，即调查基因组，环境和表型之间相互作用的生命规则的综合研究。该研究金支持研究员的研究和培训，以创新的方式为生活规则领域做出贡献。环境微生物，如细菌，可以进化分子机制，成为动物或人类宿主的疾病病原体。这是如何发生的？一种假设是，在微小真核生物（如变形虫）的捕食下生存的需要，选择了对抗真核免疫的基因的进化。然而，一种古老的真核免疫反应是拒绝病原体获得铁。成功的病原体已经进化出了对抗宿主获取铁的工具。这种分子拉锯战的结果至关重要，因为铁是一种重要的微量营养素，大多数生物体生长和生存所需。该项目的重点是如何适应捕食性阿米巴，特别是宿主-病原体争夺铁引起细菌病原体嗜肺军团菌在分子水平上进化。该研究员将与匹兹堡大学合作招募和指导学生进行研究。 宿主-病原体冲突可导致分子军备竞赛，其中宿主-病原体界面处的蛋白质结构域经受宿主和病原体快速进化的持续循环。该项目将测试这样一种假设，即争夺铁的斗争导致铁螯合基因迅速进化，这是军团菌与其天然阿米巴宿主之间分子军备竞赛的一部分。该项目利用了军团菌/网骨藻感染模型的能力和实用性。具体来说，研究员将询问MavN的演变，MavN是军团菌分泌的一种蛋白质，其功能是将铁从宿主细胞质运输到含军团菌的液泡中。MavN蛋白显示出快速进化的特征，并且这种序列多样性具有表型后果。这些特征表明，MavN可能是由于分子军备竞赛而进化的。这项工作弥合了目前进化微生物学，生物信息学和细菌学之间的鸿沟，并将使研究员能够提高和发展他们作为独立研究人员建立自己职业生涯所需的技能。该项目将使研究员获得指导，科学严谨性以及如何在STEM中培养包容性环境的培训。此外，该研究员将致力于通过加强K-12 STEM课程来增加匹兹堡地区的科学推广。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。