Mark Siegal

The genetic basis of non-genetic heterogeneity in yeast

Genetically identical cells growing in the same environment often display striking cell-to-cell heterogeneity in gene expression and other traits. Such heterogeneity is clinically important, as it is seen in microbial responses to antibiotics and in tumor cells. Nonetheless, molecular mechanisms that promote or suppress heterogeneity are poorly understood, particularly in eukaryotic organisms. I will present our work on a form of adaptive heterogeneity in the model eukaryote Saccharomyces cerevisiae (budding yeast). We developed a high-throughput, time-lapse microscopy assay to monitor variable protein

expression, growth rate and survival outcomes of tens of thousands of yeast microcolonies simultaneously. Genetically identical cells display high variation in growth rate, and slow growth correlates with higher resistance to acute heat stress. Thus, heterogeneity can serve as a bet-hedging mechanism against environmental uncertainty. I will present our work characterizing the regulatory network that controls heterogeneity, as well as our work to understand the role of heterogeneity in nature. Wild yeast strains differ in their growth-rate distributions, which suggests that heterogeneity is something that is tuned by natural selection and presents the opportunity to map natural genetic variants that underlie bet-hedging strategies.
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