How do cells make decisions?

Cells must respond appropriately to nutrient, stresses, and other signals in order to prosper. Such responses or "decisions" result from the interplay of many genes, proteins, and metabolites. I am trying to understand how microbial decisions arise out of these molecular mechanisms by studying differences in decision-making behavior across diverse strains of the budding yeast Saccharomyces cerevisiae.

To prepare or not to prepare?

Sugar consumption and GAL gene expression profiles for a strain that undergoes a diauxic shift (top) and a strain without diauxic shift, i.e. a "preparing" strain (bottom).

A common decision faced by microorganisms in nature is which nutrient(s) to consume when there are multiple options. When microbes are given a mixture of two sugars, they first consume the "preferred" sugar, then undergo a transient lag or delay in growth while inducing genes to metabolize the "alternative" sugar. The growth lag is called a "diauxic shift", and has been known since Monod's pioneering work in the 1940's. It is speculated that the diauxic shift is an adaptation to minimize the cost of expressing alternative nutrient pathways when a better nutrient is available.

However, there are many circumstances where a culture does not display a diauxic lag (Spencer et al. 2008; New et al. 2014). In a recent paper, we tried to understand how and why microbes might grow in a nutrient mixture without having a diauxic shift. We found that diauxic lag, or lack thereof, can be seen as different degrees of "preparation" for impending exhaustion of a preferred nutrient, and that this leads to a fitness tradeoff. A strain may be optimized for transitioning between nutrients or growth on a preferred nutrient, but not both.

Genetics of nutrient decisions

I am now dissecting the genetic basis of the differences in diauxie (or "preparation") across yeast strains. I hope to discover the repertoire of mutations used by nature to tune nutrient sensing, as well as the molecular basis of the fitness tradeoff we observed.

Publications

In reverse-chronological order:

Agashe D., Sane M., Phalnikar K., Diwan G. D., Habibullah A., Martinez-Gomez N. C., Sahasrabuddhe V., Polachek W., Wang J., Chubiz L. M., Marx C. J. (2015) Large-Effect Beneficial Synonymous Mutations Mediate Rapid And Parallel Adaptation In A Bacterium. PNAS (Submitted).

Wang J., Atolia E., Hua B., Savir Y., Escalante-Chong R., Springer M. (2014) Natural Variation in Preparation for Nutrient Depletion Reveals a Cost-Benefit Tradeoff. PLoS Biology. 10.1371/journal.pbio.1002041.

Escalante-Chong R., Savir Y., Carroll S. M., Ingraham J. B., Wang J., Marx C. J., Springer M. (2014) Galactose metabolic genes in yeast respond to a ratio of galactose and glucose. PNAS 112(5): 1636-1641.

Marquardt S., Escalante-Chong R., Pho N., Wang J., Churchman L. S., Springer M., Buratowski S. (2014) A chromatin-based mechanism for limiting divergent noncoding transcription. Cell 157: 1712–23. LINK