Quorum-sensing crosstalk-driven synthetic circuits: from unimodality to trimodality.
Quorum-sensing crosstalk-driven synthetic circuits: from unimodality to trimodality.
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DOI：
10.1016/j.chembiol.2014.10.008
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发表时间：
2014-12-18
影响因子：
--
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Wu F;Menn DJ;Wang X
广泛的群体感应（QS）使细菌能够进行交流，并在控制细菌毒力方面发挥着关键作用。然而，混杂的 QS 串扰的影响及其对基因调控和细胞决策的影响仍然很大程度上未知。我们系统地研究了LuxR/I和LasR/I系统之间的串扰，发现QS串扰可以分解为信号串扰和启动子串扰。使用合成正反馈电路的进一步研究表明，信号串扰显着降低了电路的双稳态电位，同时保持单峰性。然而，启动子串扰可重复地产生由噪声引起的状态转换和主机电路相互作用引起的复杂三峰响应。开发了一个集成电路非线性、随机性和主电路相互作用的数学模型，并通过实验验证了其对三模态条件的预测。这项工作结合了合成生物学和数学模型，揭示了 QS 串扰产生的复杂行为，可用于治疗和生物技术。
Widespread quorum-sensing (QS) enables bacteria to communicate and plays a critical role in controlling bacterial virulence. However, effects of promiscuous QS crosstalk and its implications for gene regulation and cell decision-making remain largely unknown. Here we systematically studied the crosstalk between LuxR/I and LasR/I systems and found that QS crosstalk can be dissected into signal crosstalk and promoter crosstalk. Further investigations using synthetic positive feedback circuits revealed that signal crosstalk significantly decreases circuit’s bistable potential while maintaining unimodality. Promoter crosstalk, however, reproducibly generates complex trimodal responses resulting from noise-induced state transitions and host-circuit interactions. A mathematical model that integrates the circuit’s nonlinearity, stochasticity, and host-circuit interactions was developed, and its predictions of conditions for trimodality were verified experimentally. Combining synthetic biology and mathematical modeling, this work sheds light on the complex behaviors emerging from QS crosstalk, which could be exploited for therapeutics and biotechnology.
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影响因子：
46.9
作者：
Canton, Barry;Labno, Anna;Endy, Drew
通讯作者：
Endy, Drew
影响因子：
56.9
作者：
Chuang, John S.;Rivoire, Olivier;Leibler, Stanislas
通讯作者：
Leibler, Stanislas
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
46.9
作者：
通讯作者：
--
DOI：
10.1073/pnas.0307571101
发表时间：
2004-04-27
影响因子：
11.1
作者：
Basu, S;Mehreja, R;Weiss, R
通讯作者：
Weiss, R