Involvement of the fission yeast GATA transcription factor Gaf1 in TOR-dependent stress and nutrient responses

2018 dissertation for MRes. The Target of Rapamycin (TOR) pathway is responsible for the growth and metabolic control of a cell, in response to nutrients and stress. This pathway, functioning through distinct protein complexes known as TORCs (TORC1 and TORC2 in yeasts and humans), is highly evolutionarily conserved. This allows for fission yeast, S. pombe, to serve as a model for humans in this study. Understanding genetic control of the TOR pathway is considered to have the potential to present pharmacological and dietary interventions for ageing and age-related diseases such as Alzheimer’s and diabetes. In this study, the highly conserved GATA transcription factor Gaf1, orthologue of GATA6 in humans, is investigated for its role in TOR by studying phenotypical and transcriptional differences between wild type and gaf1Δ cells with and without TOR inhibition. The work makes use of microfermentation experiments to determine changes in growth kinetics as well as microarray data to understand gene expression changes that might underpin these phenotypes. The results highlight the need for further investigation in this area by suggesting a complex interplay between TORC1 and TORC2 and implicating Gaf1 in both spatial and temporal aspects of cell growth. The results support recent findings of Gaf1 involvement in ncRNA expression and tRNA binding, but suggest a more complicated involvement with organonitrogen metabolism and nitrogen catabolite repression