Topology-dependent interference of synthetic gene circuit function by growth feedback

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

Research output: Contribution to journalArticle

Abstract

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. [Figure not available: see fulltext.].

Original languageEnglish (US)
Pages (from-to)695-701
Number of pages7
JournalNature Chemical Biology
Volume16
Issue number6
DOIs
StatePublished - Jun 1 2020

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Zhang, R., Li, J., Melendez-Alvarez, J., Chen, X., Sochor, P., Goetz, H., Zhang, Q., Ding, T., Wang, X., & Tian, X. J. (2020). Topology-dependent interference of synthetic gene circuit function by growth feedback. Nature Chemical Biology, 16(6), 695-701. https://doi.org/10.1038/s41589-020-0509-x