Variability in the budding yeast cell cycle: single cell experiments and stochastic network models. The variability within a clonal population of budding yeast is often larger than the variability associated with genetic differences. Fluctuations, presumably due to the low numbers of mRNA of several key cell cycle regulators, go unnoticed in datasets produced by studying aggregate contents of a population of cells. Only through single cell in vivo studies does such variation become apparent. Although the scale of variability on the single cell level and the fitness cost associated with disordered progression through the cell cycle suggest that cells are adapted to cope with molecular fluctuations, the mechanisms employed are currently unknown. With my mathematical expertise and the experimental capabilities of Fred Cross' yeast biology lab at the Rockefeller University we are well poised to tackle this question.
I aim to use time series of fluorescent markers of key cell cycle regulators from single cell experiments to design a new stochastic network model of the G1/S transition responsible for size control in budding yeast. Close collaboration with experimental biologists will allow for rapid integration of new data and for theory to influence experimental design. ? ? ?
| Skotheim, Jan M; Di Talia, Stefano; Siggia, Eric D et al. (2008) Positive feedback of G1 cyclins ensures coherent cell cycle entry. Nature 454:291-6 |
