Multistability in the lactose utilization network of Escherichia coli.

@article{citeulike:148, abstract = {Multistability, the capacity to achieve multiple internal states in response to a single set of external inputs, is the defining characteristic of a switch. Biological switches are essential for the determination of cell fate in multicellular organisms, the regulation of cell-cycle oscillations during mitosis and the maintenance of epigenetic traits in microbes. The multistability of several natural and synthetic systems has been attributed to positive feedback loops in their regulatory networks. However, feedback alone does not guarantee multistability. The phase diagram of a multistable system, a concise description of internal states as key parameters are varied, reveals the conditions required to produce a functional switch. Here we present the phase diagram of the bistable lactose utilization network of Escherichia coli. We use this phase diagram, coupled with a mathematical model of the network, to quantitatively investigate processes such as sugar uptake and transcriptional regulation in vivo. We then show how the hysteretic response of the wild-type system can be converted to an ultrasensitive graded response. The phase diagram thus serves as a sensitive probe of molecular interactions and as a powerful tool for rational network design.}, address = {Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.}, author = {Ozbudak, E. M. and Thattai, M. and Lim, H. N. and Shraiman, B. I. and Van Oudenaarden, A. }, citeulike-article-id = {148}, doi = {10.1038/nature02298}, issn = {1476-4687}, journal = {Nature}, keywords = {bistability, ecoli, lac\_operon}, month = {February}, number = {6976}, pages = {737--740}, posted-at = {2008-04-22 19:57:29}, priority = {2}, title = {Multistability in the lactose utilization network of Escherichia coli.}, url = {http://dx.doi.org/10.1038/nature02298}, volume = {427}, year = {2004} }

TY - JOUR ID - citeulike:148 L3 - citeulike-article-id:148 TI - Multistability in the lactose utilization network of Escherichia coli. JF - Nature VL - 427 IS - 6976 SP - 737 EP - 740 AD - Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. SN - 1476-4687 N2 - Multistability, the capacity to achieve multiple internal states in response to a single set of external inputs, is the defining characteristic of a switch. Biological switches are essential for the determination of cell fate in multicellular organisms, the regulation of cell-cycle oscillations during mitosis and the maintenance of epigenetic traits in microbes. The multistability of several natural and synthetic systems has been attributed to positive feedback loops in their regulatory networks. However, feedback alone does not guarantee multistability. The phase diagram of a multistable system, a concise description of internal states as key parameters are varied, reveals the conditions required to produce a functional switch. Here we present the phase diagram of the bistable lactose utilization network of Escherichia coli. We use this phase diagram, coupled with a mathematical model of the network, to quantitatively investigate processes such as sugar uptake and transcriptional regulation in vivo. We then show how the hysteretic response of the wild-type system can be converted to an ultrasensitive graded response. The phase diagram thus serves as a sensitive probe of molecular interactions and as a powerful tool for rational network design. KW - bistability KW - ecoli KW - lac_operon AU - Ozbudak, EM AU - Thattai, M AU - Lim, HN AU - Shraiman, BI AU - Van Oudenaarden, A PY - 2004/02/19/ UR - http://dx.doi.org/10.1038/nature02298 ER -