Topology-Dependent Interference of Synthetic Gene Circuit Function by Growth Feedback
Topology-Dependent Interference of Synthetic Gene Circuit Function by Growth Feedback
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DOI：
10.1038/s41589-020-0509-x
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发表时间：
2020-03
影响因子：
14.8
通讯作者：
Rong Zhang;Jiao Li;J. Melendez-Alvarez;Xingwen Chen;P. Sochor;H. Goetz;Qi Zhang;Tian Ding;Xiao Wang;Xiao-Jun Tian
中科院分区：
文献类型：
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作者：
Rong Zhang;Jiao Li;J. Melendez-Alvarez;Xingwen Chen;P. Sochor;H. Goetz;Qi Zhang;Tian Ding;Xiao Wang;Xiao-Jun Tian
合成基因回路和宿主生物之间的生长介导反馈导致多种出现的行为，包括生长双稳定性和增强的超敏感性。然而，生长反馈对基因回路的可能影响范围仍未得到充分探索。本文通过数学和实验证明了生长反馈以网络拓扑依赖的方式影响记忆电路的功能。具体来说，由于生长介导的电路产品稀释，自激活开关的记忆很快丢失。生长反馈的解耦揭示了它的记忆性，表现为它在诱导剂浓度范围内的滞回特性。相反，拨动开关对生长介导的稀释更有抵抗力，在快速生长阶段后可以恢复记忆。其基本原理在于这些回路中主动调控和抑制调控对生长介导的稀释的不同依赖。我们的研究结果揭示了生长介导的反馈如何影响基因回路行为的拓扑依赖机制。
Growth-mediated feedback between synthetic gene circuits and host organisms leads to diverse emerged behaviors, including growth bistability and enhanced ultrasensitivity. However, the range of possible impacts of growth feedback on gene circuits remains underexplored. Here we mathematically and experimentally demonstrated that growth feedback affects the functions of memory circuits in a network topology-dependent way. Specifically, the memory of the self-activation switch is quickly lost due to the growth-mediated dilution of the circuit products. Decoupling of growth feedback reveals its memory, manifested by its hysteresis property across a broad range of inducer concentration. On the contrary, the toggle switch is more refractory to growth-mediated dilution and can retrieve its memory after the fast-growth phase. The underlying principle lies in the different dependence of active and repressive regulations in these circuits on the growth-mediated dilution. Our results unveil the topology-dependent mechanism on how growth-mediated feedback influences the behaviors of gene circuits.