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

Culbertson, Edward Mclouth, Pittsburgh PA

Investigators

Abstract

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.