A quasi-integral controller for adaptation of genetic modules to variable ribosome demand
A quasi-integral controller for adaptation of genetic modules to variable ribosome demand
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DOI：
10.1038/s41467-018-07899-z
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发表时间：
2018-12-21
影响因子：
16.6
通讯作者：
Del Vecchio, Domitilla
中科院分区：
文献类型：
--
作者：
Huang, Hsin-Ho;Qian, Yili;Del Vecchio, Domitilla
遗传电路的行为往往难以预测。基因的表达水平不仅由预期的调控因子决定，而且还受其他基因表达所引起的核糖体可用性变化的影响。在这里，我们设计了一个准积分生物分子反馈控制器，使任何感兴趣的基因（GOI）的表达水平，以适应可用的核糖体的变化。反馈通过合成的小RNA（sRNA）实现，其沉默GOI的mRNA，并使用正交细胞质外功能（ECF）σ因子来感测GOI的翻译并启动sRNA转录。在没有控制子的情况下，当激活资源竞争者时，GOI的表达水平降低50%。相比之下，使用控制器，基因表达水平几乎不受竞争对手的影响。这种反馈控制器允许遗传模块适应可变的核糖体需求，从而有助于复杂电路的模块化构建。
The behavior of genetic circuits is often poorly predictable. A gene's expression level is not only determined by the intended regulators, but also affected by changes in ribosome availability imparted by expression of other genes. Here we design a quasi-integral biomolecular feedback controller that enables the expression level of any gene of interest (GOI) to adapt to changes in available ribosomes. The feedback is implemented through a synthetic small RNA (sRNA) that silences the GOI's mRNA, and uses orthogonal extracytoplasmic function (ECF) sigma factor to sense the GOI's translation and to actuate sRNA transcription. Without the controller, the expression level of the GOI is reduced by 50% when a resource competitor is activated. With the controller, by contrast, gene expression level is practically unaffected by the competitor. This feedback controller allows adaptation of genetic modules to variable ribosome demand and thus aids modular construction of complicated circuits.