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Topology-Dependent Interference of Circuit Function by Growth Feedback

By Rong Zhang, Jiao Li, Juan Melendez-Alvarez, Xingwen Chen, Patrick Sochor, Qi Zhang, Hanah Goetz, Tian Ding, Xiao Wang, Xiao-Jun Tian

Posted 05 Aug 2019
bioRxiv DOI: 10.1101/724906

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 different gene circuits remains underexplored. Here, we mathematically and experimentally demonstrated that growth feedback affects the functions of memory gene circuits in a network topology-dependent way. Specifically, the memory of the self-activation circuit is quickly lost due to the fast growth-mediated dilution of the circuit products. Decoupling of growth feedback reveals its memory, manifested by its hysteresis property across a broad range of stimulus. On the contrary, the toggle switch is more refractory to the 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.

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