Genomic approaches to studying the balance between growth versus stress defense in eukaryotic cells

Stress tolerance and rapid growth are often competing interests in cells. Upon severe environmental stress, many organisms activate defense systems concurrent with growth arrest. There has been debate as to whether aspects of the stress-activated transcriptome are regulated by stress or an indirect byproduct of reduced proliferation. For example, stressed Saccharomyces cerevisiae cells mount a common gene expression program called the environmental stress response (ESR) comprising ∼300 induced (iESR) transcripts involved in stress defense and ~600 reduced (rESR) mRNAs encoding ribosomal proteins and ribosome biogenesis factors important for division. Because ESR activation also correlates with reduced growth rate in nutrient-restricted chemostats and prolonged G1 in slow-growing mutants, an alternate proposal is that the ESR is simply a consequence of reduced division. A major challenge is that past studies did not separate effects of division arrest and stress defense; thus, the true responsiveness of the ESR – and the purpose of stress-dependent rESR repression in particular – has been unclear. In this talk, I will focus on genomic approaches, including integrative genomic analysis and single-cell transcriptomics, to test the link between growth, cell cycle progression, and ESR activation in budding yeast responding to environmental stress.