NSF Postdoctoral Fellowship in Biology FY 2021: Empirical and theoretical approaches to understanding the evolution of gene regulatory networks

Mcqueen, Eden Wellesley, Pittsburgh PA

Investigators

Abstract

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2021, 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. The project investigates the interactions between genes in the genome, which give rise to the physical traits of organisms. The specific “structures” of these interactions, that is, which genes interact to produce a trait, are often referred to as “gene regulatory networks” (GRNs). Variation in GRN structure is responsible for many differences in organismal traits, but how these structural changes to GRNs occur is not well understood. Understanding how changes to the genome alter the structure of GRNs and change traits is an important and challenging problem with broad applications. The project will tackle this problem by using sensitive techniques to investigate subtle variations of a GRN over different time scales and environments, under the mentorship of Dr. Patricia Wittkopp at the University of Michigan, and the co-mentorship a philosopher of science, Dr. Aaron Novick, to clarify practical ways to discuss and define GRNs. The Fellow will engage in teaching and outreach activities that will reach diverse audiences. The proposed work will use the genetic model system Saccharomyces cerevisiae (brewer’s yeast) to investigate GRN variation. This will be done by assessing the effects of introduced mutations on the expression levels of downstream targets of the focal GRN, specifically the TDH3 gene and its paralogs TDH1 and TDH2, using a highly sensitive high-throughput flow cytometry technique. The Fellow will examine the changes to GRN structure that have occurred within-species by quantifying the differing mutational effects on TDH3 and its paralogs. The project will also measure the effects of changing environment on the structure of these GRNs. Finally, the work will look at the focal GRN structure in a related species (S. paradoxus) to examine across-species GRN divergence. Dr. Novick’s co-sponsorship on this project adds an interdisciplinary element that will be incorporated into teaching objectives in both STEM and philosophy. The Fellow will also build a community space for early career caregivers in academia. The proposed fellowship represents an exceptional match for the career development goals of the Fellow who will receive training in a new model system, master cutting edge high-throughput data collection techniques, and receive mentoring in philosophy of science. 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.