Mark Siegal

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  The robustness continuum: yeast cells hedge their bets against unpredictable environmental change
  Mark Siegal
  Genetically identical cells grown in the same culture display striking cell-to-cell heterogeneity in gene expression and other traits. A crucial challenge is to understand how much of this heterogeneity reflects the noise tolerance of a robust system and how much serves a biological function. In some circumstances, heterogeneous traits might be favored over robust ones. For example, in bacteria cell-to-cell heterogeneity can serve as a bet-hedging mechanism, allowing a few cells to survive acute antibiotic stress while the others perish. Where a population of organisms falls on the continuum from uniformity to bet-hedging depends on the environmental regime it experiences. We describe a bet-hedging phenomenon in the yeast Saccharomyces cerevisiae, which occupies a range of natural and human-associated environments. We use a novel, high-throughput microscopy assay that monitors variable protein expression, growth rate and survival outcomes of tens of thousands of yeast microcolonies simultaneously. Clonal yeast populations display broad distributions of growth rates, and slow growth predicts resistance to acute heat stress. Expression of Tsl1, a trehalose-synthesis regulator, marks slow-growing cells and contributes to this resistance. I will present these results and discuss them in the context of the evolutionary forces shaping robust and heterogeneous traits.