Postdoctoral Fellowship: PRFB: Impact of Translation Efficiency on Immune Response Variation and Evolution

Ray, Allyson, Nashville TN

Investigators

Abstract

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2024, 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. Organisms face constant threats from parasites. Their immune response must be as effective as possible while conserving energy and minimizing damage. Immune factor production follows the central dogma of molecular biology: genes are copied to mRNA transcripts, which are then translated into proteins that then function in immunity. The speed of the immune response is a decisive factor in controlling parasite growth. Thousands of genes are transcribed in the early immune response. It takes many more steps for these transcripts to become functional, and cells struggle to keep up with the protein production demand. Deciding which transcripts to translate can then be life-or-death decisions during infection. This research combines various techniques across traditional immunology and ecoimmunology to demonstrate how protein translation regulates immunity. Furthermore, it aims to broaden participation in STEM through undergraduate research opportunities. This research will employ a combination of experimental and mathematical approaches in the red flour beetle (Tribolium castaneum) system, including cutting-edge ribosomal footprint sequencing techniques, to assess whether beetle populations differentially prioritize some transcripts over others for protein production during the early innate immune response across a panel of parasite challenges. In tandem, within-host mathematical models of immune kinetics will be built to assess translational regulation of immunity when exposure to certain parasites is unpredictable. Through the synthesis of these approaches, this research will investigate how selective translation contributes to immune specificity, determines infection trajectories, instigates tradeoffs, and drives local adaptation to unpredictable parasites. As both translation initiation machinery and innate immune signaling pathways are tightly conserved across species, this project will allow for general predictions regarding immune system regulation and evolution both within and across species. These projects will be conducted in partnership with the Maximizing Access to Research Careers (MARC) undergraduate program at Vanderbilt University, which works to broaden participation in biomedical research, to mentor at least three undergraduates on independent projects adjacent to the work proposed here. 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.