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Analysis of Circuits for Dosage Control in Microbial Populations

Walton, Sophie J. and Clamons, Samuel E. and Murray, Richard M. (2020) Analysis of Circuits for Dosage Control in Microbial Populations. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20201221-102922403

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Abstract

Designing genetic circuits to control the behaviors of microbial populations is an ongoing challenge in synthetic biology. Here we analyze circuits which implement dosage control by controlling levels of a global signal in a microbial population in face of varying cell density, growth rate, and environmental dilution. We utilize the Lux quorum sensing system to implement dosage control circuits, and we analyze the dynamics of circuits using both simplified analytical analysis and in silico simulations. We demonstrate that strong negative feedback through inhibiting LuxI synthase expression along with AiiA degradase activity results in circuits with fast response times and robustness to cell density and dilution rate. We find that degradase activity yields robustness to variations in population density for large population sizes, while negative feedback to synthase production decreases sensitivity to dilution rates.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2020.12.18.423556DOIDiscussion Paper
https://www.biorxiv.org/content/10.1101/2020.12.18.423556v1OrganizationDiscussion Paper
https://github.com/sophiejwalton/dosage_controlRelated ItemCode
ORCID:
AuthorORCID
Walton, Sophie J.0000-0003-1320-1525
Clamons, Samuel E.0000-0002-7993-2278
Murray, Richard M.0000-0002-5785-7481
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-ND 4.0 International license. This version posted December 20, 2020. We would like to thank Xinying Ren, John Marken, William Poole, and the Murray lab for useful discussions and insights throughout the project. This research is supported in part by the Institute for Collaborative Biotechnologies through contract W911NF-19-D-0001 from the U.S. Army Research Office. The content of the information on this page does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred. Code Availability: All code for figures and results of this study can be found at https://github.com/sophiejwalton/dosage_control. The authors have declared no competing interest.
Funders:
Funding AgencyGrant Number
Army Research Office (ARO)W911NF-19-D-0001
Record Number:CaltechAUTHORS:20201221-102922403
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20201221-102922403
Official Citation:Analysis of Circuits for Dosage Control in Microbial Populations. Sophie J. Walton, Samuel E. Clamons, Richard M Murray. bioRxiv 2020.12.18.423556; doi: https://doi.org/10.1101/2020.12.18.423556
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:107236
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:21 Dec 2020 18:36
Last Modified:21 Dec 2020 18:36

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