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Theoretical Design of Paradoxical Signaling-Based Synthetic Population Control Circuit in E. coli

Mayalu, Michaëlle N. and Murray, Richard M. (2020) Theoretical Design of Paradoxical Signaling-Based Synthetic Population Control Circuit in E. coli. . (Unpublished)

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We have developed a mathematical framework to analyze the cooperative control of cell population homeostasis via paradoxical signaling in synthetic contexts. Paradoxical signaling functions through quorum sensing (where cells produce and release a chemical signal as a function of cell density). Precisely, the same quorum sensing signal provides both positive (proliferation) and negative (death) feedback in different signal concentration regimes. As a consequence, the relationship between intercellular quorum sensing signal concentration and net growth rate (cell proliferation minus death rates) can be non-monotonic. This relationship is a condition for robustness to certain cell mutational overgrowths and allows for increased stability in the presence of environmental perturbations. Here, we explore stability and robustness of a conceptualized synthetic circuit. Furthermore, we asses possible design principles that could exist among a subset of paradoxical circuit implementations. This analysis sparks the development a bio-molecular control theory to identify ideal underlying characteristics for paradoxical signaling control systems.

Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription Paper
Mayalu, Michaëlle N.0000-0002-9678-0157
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-NC 4.0 International license. bioRxiv preprint first posted online Jan. 28, 2020. The authors are grateful to Leopold N. Green for help with conceptualizing circuit components within design and elucidating mechanisms. The authors acknowledge funding support from the Burroughs Wellcome Fund. The efforts depicted is also sponsored by the Defense Advanced Research Projects Agency (Agreement HR0011-17-2-0008). 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
Burroughs Wellcome FundUNSPECIFIED
Defense Advanced Research Projects Agency (DARPA)HR0011-17-2-0008
Subject Keywords:Paradoxical Signaling; Coordinated Population Control; Homeostasis; Mathematical Modeling; Stability Analysis
Record Number:CaltechAUTHORS:20200128-150452496
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Official Citation:Theoretical Design of Paradoxical Signaling-Based Synthetic Population Control Circuit in E. coli. Michaëlle N Mayalu, Richard M Murray. bioRxiv 2020.01.27.921734; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:100977
Deposited By: Tony Diaz
Deposited On:28 Jan 2020 23:24
Last Modified:16 Nov 2021 17:58

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