Metabolic gene regulation in a dynamically changing environment.
Metabolic gene regulation in a dynamically changing environment.
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DOI：
10.1038/nature07211
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发表时间：
2008-08-28
期刊：
影响因子：
64.8
通讯作者：
Hasty, Jeff
中科院分区：
文献类型：
--
作者：
Bennett, Matthew R.;Pang, Wyming Lee;Ostroff, Natalie A.;Baumgartner, Bridget L.;Nayak, Sujata;Tsimring, Lev S.;Hasty, Jeff
Natural selection dictates that cells constantly adapt to dynamically changing environments in a context-dependent manner. Gene-regulatory networks often mediate the cellular response to perturbation, and an understanding of cellular adaptation will require experimental approaches aimed at subjecting cells to a dynamic environment that mimics their natural habitat. Here, we monitor the response of S. cerevisiae metabolic gene regulation to periodic changes in the external carbon source by utilizing a microfluidic platform that allows precise, dynamic control over environmental conditions. We find that the metabolic system acts as a low-pass filter that reliably responds to a slowly changing environment, while effectively ignoring fluctuations that are too fast for the cell to mount an efficient response. We use computational modeling calibrated with experimental data to determine how frequency selection in the system is controlled by the interaction of coupled regulatory networks governing the signal transduction of alternative carbon sources. Experimental verification of model predictions leads to the discovery of two novel properties of the regulatory network. First, we reveal a previously unknown mechanism for post-transcriptional control, by demonstrating that two key transcripts are degraded at a rate that depends on the carbon source. Second, we compare two S. cerevisiae strains and find that they exhibit the same frequency response despite having markedly different induction characteristics. Our results suggest that while certain characteristics of the complex networks may differ when probed in a static environment, the system has been optimized for a robust response to a dynamically changing environment. Importantly, the integration of a novel experimental platform with numerical simulations revealed previously masked network properties, and the approach establishes a framework for dynamically probing organisms in order to reveal mechanisms that have evolved to mediate cellular responses to unpredictable environments.
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影响因子：
--
作者：
Kaniak, A;Xue, ZX;Johnston, M
通讯作者：
Johnston, M
DOI：
10.1016/j.bbrc.2005.04.119
发表时间：
2005-06-24
影响因子：
3.1
作者：
Andrade, RP;Kötter, P;Casal, M
通讯作者：
Casal, M
DOI：
10.1073/pnas.0403790102
发表时间：
2005-05-17
影响因子：
11.1
作者：
Lipan, O;Wong, WH
通讯作者：
Wong, WH
影响因子：
5.3
作者：
Rohde, JR;Trinh, J;Sadowski, I
通讯作者：
Sadowski, I
影响因子：
2.6
作者：
Sheff, MA;Thorn, KS
通讯作者：
Thorn, KS