NSF Postdoctoral Fellowship in Biology FY 2021: Deciphering how adipokine control of the epigenome impacts an organism's starvation response

Kelly, Kevin Parsons, Seattle WA

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. An accurate assessment of nutritional status is essential for survival. Fat cells signal a nutrient surplus state by secreting hormones called adipokines. Adipokines regulate decisions on several physiological processes including hunger, immunity, and reproduction. In surplus states, adipokines release a signal indicating energy resources can be devoted to costly activities like immunity and reproduction. During starvation, their secretion is reduced, signaling an energy deficit driving energy conservation. Recent evidence suggests that nuclear sequestration of the fly adipokine Upd2 is controlled by Atg8, a protein known for its role in autophagy. Furthermore, Upd2 can be forced to remain nuclear by disrupting the protein-protein interactions of Upd2 and Atg8, resulting in increased starvation resistance and promoting post-starvation hunger responses in flies. These data suggest that Upd2 and Atg8 may affect gene expression. This study seeks to determine the role of this unstudied form of adipokine-driven gene expression. The project will devote this research to teaching and mentoring high school students of underrepresented minorities through an established summer internship program to teach students basic fly research concepts and cultivate scientific interest. The project seeks to delineate how Upd2 and Atg8 modify the nuclear landscape to regulate organismal fitness during and after nutrient stress. Neither protein can bind DNA, so DNA/Chromatin binding proteins associated with Upd2 and Atg8 will be determined via immunoprecipitation. The project will determine where Upd2 binds to the genome using the CUT&Tag method of epigenomic profiling. In conjuction, a differential expression profile of genes associated with changes in nutrient state will be generated using RNAseq. Data from both analyses will be combined using current computational approaches to identify candidate genes regulated by Upd2 in a nutrient-dependent manner. Candidate genes will be mutated in the fly model for feeding behavior analysis during fed and starvation conditions to prove their involvement in the nutrient sensing response. This behavioral screening will provide a fun and simple way to introduce undergraduates to basic concepts of fly research and the Fellow will receive new experience and training in this study system as well. 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.