Understanding the Role of the PLA2G6 Gene in Neuromuscular Degeneration and Female Infertility

Abstract

The PLA2G6 gene is being studied intensely as it has been linked with various neurodegenerative diseases. Researchers often use Drosophila as a model for human diseases due to its short lifespan, its tendency to quickly reproduce, its genetic accessibility and its high degree of evolutionary conservation with humans. Interestingly, when PLA2G6 was knocked out in flies, they exhibited symptoms of neurodegeneration. To study the relationship between PLA2G6 and neurodegeneration, it is possible to phenocopy these symptoms by knocking down PLA2G6 exclusively in the neurons. Firstly, my research focuses on understanding the role of PLA2G6 in specific neuronal subtypes in Drosophila. Interestingly, my mentor’s lab demonstrated that flies with a ubiquitous knockdown of the PLA2G6 gene display more severe locomotor defects than flies with a pan-neuronal knockdown, leading them to posit that PLA2G6 also contributes to locomotor ability in tissues other than neurons. My research, therefore, also focuses on the role of PLA2G6 in muscle cells. Next, I investigate whether PLA2G6 and a related gene, parkin, interact, leading to more severe phenotypes when these genes are both disrupted. Lastly, the lab noticed that PLA2G6 mutant flies had female fertility defects, leading them to believe that cellular processes driven by PLA2G6 may act to affect germ cells, as well. For that reason, I additionally investigate the role of PLA2G6 in female infertility. My experiments will contribute to a more elaborate understanding of the PLA2G6 gene so that we can further piece together the cellular processes that are disturbed when this gene is mutated in human disease patients.