Engineering modular and tunable genetic amplifiers for scaling transcriptional signals in cascaded gene networks.
Engineering modular and tunable genetic amplifiers for scaling transcriptional signals in cascaded gene networks.
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DOI：
10.1093/nar/gku593
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发表时间：
2014-08
影响因子：
14.9
通讯作者：
Buck M
中科院分区：
文献类型：
--
作者：
Wang B;Barahona M;Buck M
合成生物学旨在控制和重新编程活细胞内的信号处理途径，以实现重新利用的有益应用。在这里，我们报告的设计和建设的一组模块化和增益可调的基因放大器在大肠杆菌能够放大的转录信号与广泛的可调增益控制级联基因网络。这些装置是使用来自假单胞菌中hrp（过敏反应和致病性）基因调控网络的正交遗传组分（hrpRS、hrpV和PhrpL）进行工程改造的。放大器可以线性放大高达21倍的转录输入，具有大的输出动态范围，但在信号放大过程中不会引入显著的时间延迟或显著的噪声。该组基因放大器通过改变装置中潜在的无配体激活蛋白的表达水平来实现不同的增益和输入动态范围。作为它们的电子对应物，这些工程化的转录放大器可以通过可预测地和动态地调节转录信号流来实现高级的细胞内和细胞外控制功能，从而在生物系统的设计中充当基本构建块。
Synthetic biology aims to control and reprogram signal processing pathways within living cells so as to realize repurposed, beneficial applications. Here we report the design and construction of a set of modular and gain-tunable genetic amplifiers in Escherichia coli capable of amplifying a transcriptional signal with wide tunable-gain control in cascaded gene networks. The devices are engineered using orthogonal genetic components (hrpRS, hrpV and PhrpL) from the hrp (hypersensitive response and pathogenicity) gene regulatory network in Pseudomonas syringae. The amplifiers can linearly scale up to 21-fold the transcriptional input with a large output dynamic range, yet not introducing significant time delay or significant noise during signal amplification. The set of genetic amplifiers achieves different gains and input dynamic ranges by varying the expression levels of the underlying ligand-free activator proteins in the device. As their electronic counterparts, these engineered transcriptional amplifiers can act as fundamental building blocks in the design of biological systems by predictably and dynamically modulating transcriptional signal flows to implement advanced intra- and extra-cellular control functions.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
12.6
作者：
Wang, Baojun;Barahona, Mauricio;Buck, Martin
通讯作者：
Buck, Martin
DOI：
10.1073/pnas.0408507102
发表时间：
2005-03-08
影响因子：
11.1
作者：
Hooshangi, S;Thiberge, S;Weiss, R
通讯作者：
Weiss, R
影响因子：
3.9
作者：
Varadarajan, Prasanna Amur;Del Vecchio, Domitilla
通讯作者：
Del Vecchio, Domitilla
影响因子：
46.9
作者：
Dahl, Robert H.;Zhang, Fuzhong;Keasling, Jay D.
通讯作者：
Keasling, Jay D.