Investigating uncharacterised epigenetic regulators in the C. elegans germline

Abstract

Epigenetics refers to the molecular signals that control the activation and repression of genes. These signals are important for several biological processes ranging from gametogenesis to development, and to the development of complex disease. Additionally, there is growing evidence that they can be inherited from one generation to the next, challenging traditional understanding of heredity. To fully comprehend how epigenetic mechanisms contribute to germline development and function, we must understand how the germline regulates, and is regulated by, these epigenetic processes. In this thesis, I use Caenorhabditis elegans as a model to explore understudied players in germline epigenetic regulation. The findings span numerous facets of epigenetic regulation, from chromatin to small RNA and the spatial organisation of biomolecules into phase-separating granules. I provide an overview of the burgeoning intersection between the fields of epigenetics and evolutionary biology, giving broader context for the potential implications of epigenetic inheritance. I synthesise existing data on protein-protein interactions in the germline granule context, developing a resource to better inform future investigations in this area. I investigate two uncharacterised genes in detail, using a range of phenotypic, transcriptomic and proteomic analyses to probe their functions, with a focus on their roles in germline epigenetics. Lastly, I explore the writing and reading of an underexplored histone modification which has been implicated in transgenerational effects but is lacking characterisation of its precise function and regulation in the germline. This thesis broadens the network of genes that play a role in germline epigenetics in C. elegans. It opens several new avenues of investigation that future work can build on to further expand our understanding of how epigenetics is regulated in the germline, and how it can contribute to complex phenotypes.