Effects of growth feedback on gene circuits: A dynamical understanding
Effects of growth feedback on gene circuits: A dynamical understanding
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DOI：
10.1101/2023.06.06.543915
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发表时间：
2023-06
期刊：
影响因子：
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通讯作者：
Ling-Wei Kong;Wenjia Shi;Xiao-Jun Tian;Ying-Cheng Lai
中科院分区：
文献类型：
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作者：
Ling-Wei Kong;Wenjia Shi;Xiao-Jun Tian;Ying-Cheng Lai
由于电路-宿主相互作用，例如生长反馈，将工程基因电路成功整合到宿主细胞中仍然是合成生物学中的重大挑战，其中电路影响细胞生长，反之亦然。了解电路故障的动态变化并识别对增长反馈有弹性的拓扑结构对于基础研究和应用研究都至关重要。利用转录调控电路与适应作为一个范例，我们系统地研究了435个不同的拓扑结构，并发现六类故障。电路故障的三种动力学机制被确定为：响应曲线的连续变形，加强或诱导振荡，以及突然切换到共存吸引子。我们广泛的计算还揭示了电路鲁棒性措施和增长反馈的强度之间的比例律。尽管大多数电路拓扑结构的增长反馈的负面影响，我们确定了一些电路，保持最佳性能的设计，一个重要的应用功能。
The successful integration of engineered gene circuits into host cells remains a significant challenge in synthetic biology due to circuit-host interactions, such as growth feedback, where the circuit influences cell growth and vice versa. Understanding the dynamics of circuit failures and identifying topologies resilient to growth feedback are crucial for both fundamental and applied research. Utilizing transcriptional regulation circuits with adaptation as a paradigm, we systematically study 435 distinct topological structures and uncover six categories of failures. Three dynamical mechanisms of circuit failures are identified: continuous deformation of the response curve, strengthened or induced oscillations, and sudden switching to coexisting attractors. Our extensive computations also uncover a scaling law between a circuit robustness measure and the strength of growth feedback. Despite the negative effects of growth feedback on the majority of circuit topologies, we identify a few circuits that maintain optimal performance as designed, a feature important for applications.