A rationally engineered decoder of transient intracellular signals.

A rationally engineered decoder of transient intracellular signals.
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DOI:
10.1038/s41467-021-22190-4
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发表时间:
2021-03-25
影响因子:
16.6
通讯作者:
Stelling J
Stelling J
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Lormeau C;Rudolf F;Stelling J

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细胞可以通过调节信号动力学和相应的反应来编码有关其环境的信息。然而,当细胞只对瞬时信号做出反应时,细胞用于解码这些动态的机制仍然未知。在这里,我们的方法,这种解码的设计原则,合理的工程合成短脉冲解码器在芽殖酵母。TopoDesign是一种用于快速原型设计的计算方法,它允许我们探索4122种可能的电路架构,设计有针对性的实验,然后合理地选择单个电路进行实施。该电路通过非相干前馈和正反馈演示了短脉冲解码。我们预测非相干前馈解码瞬态信号是必不可少的,从而补充提出的设计原则的时间滤波,持续的信号,但不是瞬态信号的响应能力。更一般地说,我们预计TopoDesign可以帮助设计其他具有非直观动力学的合成电路,只需组装可用的生物组件。细胞通过调节信号动力学来编码信息。在这里,作者开发了一个快速原型工具TopoDesign,在酵母中设计合成短脉冲解码器。
Cells can encode information about their environment by modulating signaling dynamics and responding accordingly. Yet, the mechanisms cells use to decode these dynamics remain unknown when cells respond exclusively to transient signals. Here, we approach design principles underlying such decoding by rationally engineering a synthetic short-pulse decoder in budding yeast. A computational method for rapid prototyping, TopoDesign, allowed us to explore 4122 possible circuit architectures, design targeted experiments, and then rationally select a single circuit for implementation. This circuit demonstrates short-pulse decoding through incoherent feedforward and positive feedback. We predict incoherent feedforward to be essential for decoding transient signals, thereby complementing proposed design principles of temporal filtering, the ability to respond to sustained signals, but not to transient signals. More generally, we anticipate TopoDesign to help designing other synthetic circuits with non-intuitive dynamics, simply by assembling available biological components. Cells encode information by modulating signal dynamics. Here the authors developed a rapid prototyping tool, TopoDesign, to engineer a synthetic short-pulse decoder in yeast.
DOI: 10.1038/s41467-021-22190-4
发表时间: 2021-03-25
影响因子: 16.6
作者:
Lormeau C;Rudolf F;Stelling J
通讯作者: Stelling J
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