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Host-circuit interactions explain unexpected behavior of a gene circuit. ?

机译：宿主电路相互作用解释了基因电路的意外行为。 ？

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摘要

Mathematical models are powerful tools for the design of gene circuits in synthetic biology. Models can predict circuit behavior and guide the selection of suitable circuit components and implementations. The increasing complexity synthetic circuits typically requires model approximations that are amenable for analysis and parameter estimation. However, these simpler models may not reflect the actual behavior of a synthetic circuit once implemented in a host of interest. The experimental implementation of a circuit may show dynamics that cannot be accounted by simplified models. Potential sources for unexpected circuit behavior are host-circuit interactions through competition for shared cellular resources. The allocation of cellular resources to circuit expression inevitably reduces those resources available to other cellular functions such as growth and biosynthesis. Yet the balance between circuit function and host physiology is often overlooked at the design stage. Here we integrate a model of a synthetic circuit, the incoherent feedforward loop, with a mechanistic model for cell growth. We show how the integrated model explains measured circuit responses that the circuit-only model was unable to predict. Our results provide evidence that anomalous circuit dynamics can be traced back to host-circuit interactions.
机译：数学模型是用于合成生物学中基因电路设计的强大工具。模型可以预测电路行为，并指导选择合适的电路组件和实现。越来越复杂的合成电路通常需要适用于分析和参数估计的模型近似。但是，一旦在感兴趣的主机中实现，这些较简单的模型可能无法反映合成电路的实际行为。电路的实验实现可能会显示简化模型无法解释的动力学。电路意外行为的潜在来源是通过竞争共享蜂窝资源而发生的主电路交互。将细胞资源分配给电路表达不可避免地减少了可用于其他细胞功能（例如生长和生物合成）的那些资源。然而，电路功能和宿主生理之间的平衡通常在设计阶段就被忽略了。在这里，我们将合成电路模型（非相干前馈环路）与细胞生长的机械模型集成在一起。我们将展示集成模型如何解释仅电路模型无法预测的测量电路响应。我们的结果提供了证据，异常电路动力学可以追溯到主电路相互作用。

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