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Architectures for Combined Transcriptional and Translational Resource Allocation Controllers.
Cell Systems ( IF 9.3 ) Pub Date : 2020-09-15 , DOI: 10.1016/j.cels.2020.08.014
Alexander P S Darlington 1 , Declan G Bates 1
Affiliation  

Recent work on engineering synthetic cellular circuitry has shown that non-regulatory interactions mediated by competition for gene expression resources can result in degraded performance or even failure. Transcriptional and translational resource allocation controllers based on orthogonal circuit-specific gene expression machinery have separately been shown to improve modularity and circuit performance. Here, we investigate the potential advantages, challenges, and design trade-offs involved in combining transcriptional and translational controllers into a “dual resource allocation control system.” We show that separately functional, translational, and transcriptional controllers cannot generally be combined without extensive redesign. We analyze candidate architectures for direct design of dual resource allocation controllers and propose modifications to improve their performance (in terms of decoupling and expression level) and robustness. We show that dual controllers can be built that are composed only of orthogonal gene expression resources and demonstrate that such designs offer both superior performance and robustness characteristics.



中文翻译:

组合转录和翻译资源分配控制器的架构。

最近关于工程合成细胞电路的工作表明,由对基因表达资源的竞争介导的非调节相互作用会导致性能下降甚至失败。基于正交电路特定基因表达机制的转录和翻译资源分配控制器已分别被证明可以提高模块性和电路性能。在这里,我们研究了将转录和翻译控制器组合成“双资源分配控制系统”所涉及的潜在优势、挑战和设计权衡。我们表明,如果不进行广泛的重新设计,通常不能将单独的功能、翻译和转录控制器结合起来。我们分析了直接设计双资源分配控制器的候选架构,并提出修改建议以提高其性能(在解耦和表达水平方面)和稳健性。我们表明可以构建仅由正交基因表达资源组成的双控制器,并证明这种设计提供了卓越的性能和稳健性特征。

更新日期:2020-10-30
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