Stability of cellular memory

30 September 2005

Alexander van Oudenaarden


Multistability, the capacity to achieve multiple internal states in response to a single set of external inputs, is the essence of a biological switch. Biological switches underlie such processes as the determination of cell fate in multicellular organisms, the regulation of cell cycle oscillations, and the propagation of epigenetic traits in microbes. The defining characteristic of a switch is that, once its internal state has been set or reset by a transient external stimulus, that state is maintained even in the absence of stimuli. Multistable network therefore have the potential to store information on prior stimuli. In this talk I will use discuss theoretical tools that can be used to characterize multistable gene networks. Additionally I will show how stochastic fluctuations in the concentrations of regulatory proteins limit the stability of cellular memory. Finally I will speculate about which evolutionary role bistability and noise could play. I will show that, during growth in fluctuating environments, a dynamically bistable population can sometimes achieve a higher net growth rate than a homogenous one.


M Acar, A Becskei, A van Oudenaarden, "Enhancement of cellular memory by reducing stochastic transitions,", Nature 435:228-32 2005. PDF

M Thattai, A van Oudenaarden, "Stochastic gene expression in fluctuating environments,", Genetics 167:523-30 2004. PDF.

E M Ozbudak, M Thattai, H N Lim, B I Shraiman, A van Oudenaarden, "Multistability in the lactose utilization network of Escherichia coli", Nature 427:737-40 2004. PDF.

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