Stochastic Start in the budding yeast cell cycle

描述（由申请人提供）：出芽酵母细胞周期的可变性：单细胞实验和随机网络模型。芽殖酵母克隆群体内的变异性往往大于与遗传差异相关的变异性。波动可能是由于几种关键细胞周期调节因子的mRNA数量较少，在研究细胞群体的总含量产生的数据集中未被注意到。只有通过单细胞体内研究，这种变异才变得明显。尽管单细胞水平上的可变性规模以及与细胞周期无序进展相关的适应度成本表明，细胞适应于应对分子波动，但所采用的机制目前尚不清楚。凭借我的数学专业知识和洛克菲勒大学弗雷德·克罗斯酵母生物学实验室的实验能力，我们已经准备好解决这个问题。我的目标是利用单细胞实验中关键细胞周期调节因子的时间序列荧光标记来设计一个新的G1/S过渡的随机网络模型，该模型负责出芽酵母的大小控制。与实验生物学家的密切合作将使新数据的快速整合和理论影响实验设计成为可能。

DESCRIPTION (provided by applicant): 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.