The Impact of H3.3 Glycine (G) 34 to Tryptophan (W) Mutation on the Fat Body

Abstract

Histone 3.3 Glycine (G) 34 to Tryptophan (W) mutation is a rare post-zygotic mutation that has been discovered to be implicated in 90% of giant cell tumor bone cases. Following previous RNA sequencing data on the expression of H3.3G34W on the somatic muscle of Drosophila melanogaster, it was revealed that there was deregulation of genes associated with lipid metabolism and also lethality at the pupal developmental stage. Following these findings, we aim to investigate the phenotypic effect of expressing H3.3 G34W specifically on the fat body tissue (organ of lipid metabolism) and the lipid droplets of Drosophila melanogaster, leveraging the UAS-GAL4 system.

Furthermore, we aim to assess the effect of fat body specific expression of H3.3G34W mutation on the survival, size and systemic behavior of Drosophila melanogaster. Additionally, to build on prior findings from the RNA-seq data, we aim to also assess the impact of somatic muscle specific H3.3G34W expression on the size of Drosophila melanogaster third instar larvae. Overall, this study will offer insights into the impact of H3.3G34W on metabolic regulation and potentially pave the way for new therapeutic strategies by targeting the affected lipid metabolic pathways.