Department of Systems & Computational Biology


Departmental Seminar



Variability and robustness: lessons from single-cell traits in yeast


Mark Siegal, Ph.D.

Center for Genomics and Systems Biology

New York University

Monday, February 27, 2017

LeFrak Auditorium

Price Center



Abstract: 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. We use the model eukaryote and opportunistic pathogen Saccharomyces cerevisiae (budding yeast) to study these mechanisms. I will present our work using high-throughput morphometric analysis of individual yeast cells to investigate genes controlling the amount of variation in cell shape. This work argues against the longstanding view that the molecular chaperone Hsp90 buffers traits against the effects of mutations. I will also present our work on a form of beneficial heterogeneity in yeast. We developed a highly parallel, 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 expression of stress-protective gene products and with higher tolerance of acute heat stress. Thus, heterogeneity can serve as a bet-hedging mechanism against environmental uncertainty.

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