Mutations in ribosome protein (Rp) genes and ribosome biogenesis factors result in debilitating diseases known as ribosomopathies. Cells heterozygous mutant for Rp genes (Rp/+) also get eliminated when mixed with wild-type cells by cell competition. The competitive elimination of less fit cells is implicated in development of tissues and in diseases like cancer. Recent studies in Drosophila have focused on how Rp/+ cells experience stress pathway activation and transcriptional changes as an adaptation to the loss of a copy of a ribosomal gene. Some of these observations have led us to investigate the role of the Gr64 family of proteins in alleviating proteotoxic stress in Rp/+ cells and subsequently identify that occurs via calcium signalling. At the same time, the transcriptional profile of Rp/+ cells hints at many more alterations that have yet to be characterised. Our data also show that Rp/+ cells have differential expression of a great number of metabolic enzymes and membrane transporter proteins. These findings hint at metabolic alterations that occur in Rp/+ cells and thus a role for metabolism in cell competition. I have expanded on these observations and found that several metabolic pathways appear to be important in determining the fate of loser Rp/+ cells, such as the tricarboxylic acid cycle and glutathione biosynthesis. I present my findings on calcium signalling and metabolism in this thesis, with the aim to create a better understanding of mosaic winner-loser wing discs that undergo cell competition.
The role of calcium signalling and metabolism in cell competition induced by ribosome gene mutations.
Mastrogiannopoulos, A. A. (Author). 9 May 2023
Student thesis: Doctoral Thesis › Doctor of Philosophy (PhD)