Dichotomous feedback: a signal sequestration-based feedback mechanism for biocontroller design.

Dichotomous feedback: a signal sequestration-based feedback mechanism for biocontroller design.
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DOI:
10.1098/rsif.2021.0737
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发表时间:
2022-04
期刊:
Journal of the Royal Society, Interface
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我们引入了一种新的设计框架,用于在合成生物学中实施负反馈调节,我们将其称为“二分反馈”。我们的方法与当前方法的不同之处在于,它隔离了要控制的过程中的现有通量,并以这种方式利用过程的架构来设计控制律。这种信号隔离机制出现在许多自然生物系统中,并且可能比“分子隔离”和当今生物分子反馈控制设计中常见的其他比较基序更容易实现。通过将信号隔离的强度与过程输出联系起来来闭合环路。我们的反馈调节机制是由双组分信号系统驱动的,其中第二个响应调节器可以与自然响应调节器竞争,从而隔离激酶活性。这里,二分反馈是通过随着自然过程的输出水平的增加而增加第二响应调节剂的浓度来建立的。广泛的分析展示了这种类型的反馈如何塑造信号响应、衰减固有噪声,同时提高鲁棒性并减少串扰。
We introduce a new design framework for implementing negative feedback regulation in synthetic biology, which we term ‘dichotomous feedback’. Our approach is different from current methods, in that it sequesters existing fluxes in the process to be controlled, and in this way takes advantage of the process’s architecture to design the control law. This signal sequestration mechanism appears in many natural biological systems and can potentially be easier to realize than ‘molecular sequestration’ and other comparison motifs that are nowadays common in biomolecular feedback control design. The loop is closed by linking the strength of signal sequestration to the process output. Our feedback regulation mechanism is motivated by two-component signalling systems, where a second response regulator could be competing with the natural response regulator thus sequestering kinase activity. Here, dichotomous feedback is established by increasing the concentration of the second response regulator as the level of the output of the natural process increases. Extensive analysis demonstrates how this type of feedback shapes the signal response, attenuates intrinsic noise while increasing robustness and reducing crosstalk.
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