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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 (2020) Bistable State Switch Enables Ultrasensitive Feedback Control in Heterogeneous Microbial Populations. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20201111-093413972

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Abstract

Molecular feedback control circuits can improve robustness of gene expression at the 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 the 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 to avoid burden across all cells. 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:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2020.11.10.377051DOIDiscussion Paper
ORCID:
AuthorORCID
Cuba Samaniego, Christian0000-0003-1858-2259
Murray, Richard M.0000-0002-5785-7481
Franco, Elisa0000-0003-1103-2668
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. This version posted November 10, 2020. 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.
Funders:
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
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20201111-093413972
Official Citation:Bistable State Switch Enables Ultrasensitive Feedback Control in Heterogeneous Microbial Populations Xinying Ren, Christian Cuba Samaniego, Richard M Murray, Elisa Franco bioRxiv 2020.11.10.377051; doi: https://doi.org/10.1101/2020.11.10.377051
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:106609
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:11 Nov 2020 17:55
Last Modified:11 Nov 2020 17:55

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