Emergent bistability by a growth-modulating positive feedback circuit.
Emergent bistability by a growth-modulating positive feedback circuit.
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DOI：
10.1038/nchembio.218
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发表时间：
2009-11
影响因子：
14.8
通讯作者：
You, Lingchong
中科院分区：
文献类型：
--
作者：
Tan, Cheemeng;Marguet, Philippe;You, Lingchong
一个合成的基因电路通常是通过将宿主细胞视为一个不变的“底盘”来设计的。然而，电路激活可能会调节宿主的生理，而这反过来又会对电路行为产生重大影响。我们通过一个简单的电路来说明这一点，该电路由突变的T7RNA聚合酶(T7RNAP*)组成，它激活了自己在大肠杆菌中的表达。尽管T7 RNAP*的激活是非合作的，但该回路导致了双稳定基因的表达。这种违反直觉的观察可以用回路激活导致的生长迟缓来解释，这导致了T7 RNAP*在单个细菌中的非线性稀释。解释这种影响的模型所作的预测得到了进一步的实验测量的验证。我们的结果揭示了一种产生双稳态的新机制，并强调了在设计基因电路时考虑宿主生理调节的必要性。
A synthetic gene circuit is often engineered by considering the host cell as an invariable “chassis”. Circuit activation, however, may modulate host physiology, which in turn can drastically impact circuit behavior. We illustrate this point by a simple circuit consisting of mutant T7 RNA polymerase (T7 RNAP*) that activates its own expression in bacterium Escherichia coli. Although activation by the T7 RNAP* is noncooperative, the circuit caused bistable gene expression. This counterintuitive observation can be explained by growth retardation caused by circuit activation, which resulted in nonlinear dilution of T7 RNAP* in individual bacteria. Predictions made by models accounting for such effects were verified by further experimental measurements. Our results reveal a novel mechanism of generating bistability and underscore the need to account for host physiology modulation when engineering gene circuits.
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DOI：
10.1073/pnas.0500345102
发表时间：
2005-07-05
影响因子：
11.1
作者：
Kramer, BP;Fussenegger, M
通讯作者：
Fussenegger, M
影响因子：
46.9
作者：
Kramer, BP;Viretta, AU;Fussenegger, M
通讯作者：
Fussenegger, M
影响因子：
64.8
作者：
Dekel, E;Alon, U
通讯作者：
Alon, U
影响因子：
30.8
作者：
Lim, Han N.;van Oudenaarden, Alexander
通讯作者：
van Oudenaarden, Alexander
影响因子：
4.4
作者：
Haseltine, Eric L.;Arnold, Frances H.
通讯作者：
Arnold, Frances H.