Genomic analysis of the heat shock response and its relationship to growth rate in Saccharomyces cerevisiae

Like other single cell organisms, the baker's yeast Saccharomyces cerevisiae has evolved the ability to respond to a variety of environment stresses. Much of our current understanding of yeast's stress response comes from induction-based studies such as the microarray, and high throughput screening of systematic deletion library. I have applied these two types of tools to study the yeast heat shock response.Previous large scale microarray experiments have identified a common set of gene expression pattern to a many type of environmental stress. However, more recent work also demonstrated that the same set of genes is also highly correlated with growth rate. The significant overlap between those two groups of genes suggests that much of the previously identified stress response genes could simply be the effect of slow-growth. I address this issue by examining the effect of growth rate on the heat shock response. I find compelling evidence that slow-growing cells behave as if they are under stress. At the gene expression level, most of the stress response is fully active at slow-growth. As a result, the magnitude of the stress response of slow-growing cells is smaller than fast-growing ones. At the physiological level, slow-growth confers increased thermotolerance to lethal heat shocks. While the induction of stress response of slow-growing cells can be attributed to an increased respiratory activity, it fails to explain the increased heat resistance of cells at low growth rate.I also took advantage of the yeast deletion library and applied barcode sequencing to screen for genes important for heat shock survival. Unlike induction-based methods, I found a small number of genes whose absence results in hypersensitivity to heat. Furthermore, there also appears to be very little correlation between the rate of gene expression induction and a gene's importance for heat shock survival. Unlike mild heat shock, the apparent lack of gene expression response to lethal heat shock suggest that factors important for heat shock survival cannot be identified through gene expression experiments and most likely act at the level of protein.