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

这一行动为NSF 2022财年生物学博士后研究奖学金提供了资金，综合研究调查了基因组、环境和表型之间相互作用的生命规则。该奖学金支持研究员的研究和培训，这些研究员将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。这种情况是如何发生的？一种假设是，需要在微型真核生物(如阿米巴)的捕食中幸存下来，这是对抗真核免疫的基因进化的选择。然而，一种古老的真核免疫反应是拒绝病原体接触铁。成功的病原体进化出了对抗宿主获取铁的工具。这场分子拉锯战的结果至关重要，因为铁是一种至关重要的微量营养素，是大多数生物体生长和生存所必需的。这个项目的重点是如何适应捕食性阿米巴，特别是宿主-病原体对铁的争夺，导致细菌病原体嗜肺军团菌在分子水平上进化。这位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-病原体的冲突可能导致分子军备竞赛，宿主-病原体界面的蛋白质结构域受到宿主和病原体快速进化的持续循环的影响。该项目将检验这样一种假设，即对铁的争夺导致铁储存基因迅速进化，这是军团菌与其天然变形虫宿主之间的分子军备竞赛的一部分。该项目充分利用了军团菌/网枝菌感染模型的强大功能和实用性。具体地说，这位研究员将询问MavN的进化，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输送到含有军团菌的液泡中。MavN蛋白显示出快速进化的特征，这种序列多样性具有表型后果。这些特征表明，MavN可能由于分子军备竞赛而进化。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，并将使该研究员能够增强和发展他们作为独立研究人员建立自己的职业生涯所需的技能。该项目将使该研究员能够在指导、科学严谨以及如何在STEM中促进包容性环境方面获得培训。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，并通过使用基金会的智力优势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 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.