The Regulation of Polyploidy in Health and Disease

Project Summary Polyploidy frequently arises in response to injury, aging, and disease. Despite its prevalence, major gaps exist in our understanding of how polyploid cells alter cell, tissue, and organ physiology. This is part because polyploid cells are heterogeneous and arise in distinct ploidy states (mononucleated and multinucleated) with each nucleus having varying sets of chromosomes. It is therefore hypothesized that the heterogeneity of ploidy states provides cells with a vast repertoire of mechanisms for tissue growth, repair, and adaption to stress. Using the fruit fly, Drosophila melanogaster, as a model my laboratory has identified the core cellular and genetic mechanisms regulating polyploid cell growth in epithelial wound repair and aging as well as novel physiological roles for polyploidy in resistance to genotoxic stress and enhancing tissue mechanics. Since mononucleated and multinucleated cells arise in adult Drosophila epithelium in response to injury, similar to vertebrates, we can determine how a cell’s ploidy state affects its cellular, tissue, and organ physiology and disease susceptibility. The goals of this project are to 1) determine how ploidy state, both mononucleated and multinucleated epithelial cells responds to and protect against UV-induced DNA damage and 2) elucidate how ploidy state alters a cell’s actomyosin network to enhance epithelial tension and restore organ movement in the fruit fly post wound repair. Doing so, will provide fundamental insights into the versatility of polyploidy and how a cell’s ploidy state impacts human health and disease.