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Bistable State Switch Enables Ultrasensitive Feedback Control in Heterogeneous Microbial Populations

Ren, Xinying and Cuba Samaniego, Christian and Murray, Richard M. and Franco, Elisa (2021) Bistable State Switch Enables Ultrasensitive Feedback Control in Heterogeneous Microbial Populations. In: 2021 American Control Conference (ACC). IEEE , Piscataway, NJ, pp. 652-659. ISBN 978-1-6654-4197-1.

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Molecular feedback control circuits can improve robustness of gene expression at single cell-level. This achievement can be offset by requirements of rapid protein expression, that may induce cellular stress, known as burden, that reduces colony growth. To begin to address this challenge we take inspiration by ‘division-of-labor’ in heterogeneous cell populations: we propose to combine bistable switches and quorum sensing systems to coordinate gene expression at population-level. We show that bistable switches in individual cells operating in parallel yield an ultrasensitive response, while cells maintain heterogeneous levels of gene expression. Within a feedback loop, these switches can achieve robust reference tracking and adaptation to disturbances at the population-level. We also demonstrate that molecular sequestration enables tunable hysteresis in individual switches, making it possible to obtain a wide range of stable population-level expressions.

Item Type:Book Section
Related URLs:
URLURL TypeDescription Paper
Cuba Samaniego, Christian0000-0003-1858-2259
Murray, Richard M.0000-0002-5785-7481
Franco, Elisa0000-0003-1103-2668
Additional Information:© 2021 AACC. The authors would like to thank Fangzhou Xiao, Ronghui Zhu and Nicholas A Delateur for their insightful discussions. The author XR is sponsored by the Defense Advanced Research Projects Agency (Agreement HR0011-17-2-0008). The authors EF and CCS acknowledge support by NSF/BBSRC award 2020039. The content of the information does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred.
Funding AgencyGrant Number
Defense Advanced Research Projects Agency (DARPA)HR0011-17-2-0008
Biotechnology and Biological Sciences Research Council (BBSRC)2020039
Record Number:CaltechAUTHORS:20201111-093413972
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Official Citation:X. Ren, C. C. Samaniego, R. M. Murray and E. Franco, "Bistable State Switch Enables Ultrasensitive Feedback Control in Heterogeneous Microbial Populations," 2021 American Control Conference (ACC), 2021, pp. 652-659, doi: 10.23919/ACC50511.2021.9482836
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:106609
Deposited By: Tony Diaz
Deposited On:11 Nov 2020 17:55
Last Modified:25 Aug 2021 16:51

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