The Gresham lab studies the regulation of cell growth and the regulation of mRNA decay. We use the budding yeast (Saccharomyces cerevisiae) as a model system and a combination of genetic, genomic and computational methods to address these questions.
Systems biology of cell growth and quiescence
We are interested in the regulation of cell growth and how it is coordinated with progression through the cell cycle, metabolism and biogenesis of macromolecules such as ribosomes. To control the growth rate of cells we use chemostats, which allow us to systematically study the metabolic, physiological and molecular programs associated with different rates of cell growth. We are taking a variety of approaches to study how cell growth is regulated including:
-the study of mutants selected in nutrient-limited chemostats with increased growth rates
-mapping QTL that underlie variation in growth rate in natural isolates of yeast
-using massively parallel phenotyping to identify genetic interactions relevant to the regulation of cell growth and quiescence.
Regulation of mRNA decay
The fastest way to remodel global transcriptional states is to regulate the stability of existing populations of messenger RNAs. In response to particular extracellular stimuli we have found that the half-life of specific transcripts is dramatically decreased. We are studying how the fate of mRNAs is regulated using a variety of approaches including:
-in vivo labeling of mRNAs
-kinetic studies of mRNA synthesis and decay
-identification of cis and trans factors that alter mRNA decay rates