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Context Dependence of Biological Circuits

Catanach, Thomas A. and McCardell, Reed and Baetica, Ania-Ariadna and Murray, Richard M. (2018) Context Dependence of Biological Circuits. . (Unpublished)

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It has been an ongoing scientific debate whether biological parameters are conserved across experimental setups with different media, pH values, and other experimental conditions. Our work explores this question using Bayesian probability as a rigorous framework to assess the biological context of parameters in a model of the cell growth controller in You et al. When this growth controller is uninduced, the E. coli cell population grows to carrying capacity; however, when the circuit is induced, the cell population growth is regulated to remain well below carrying capacity. This growth control controller regulates the E. coli cell population by cell to cell communication using the signaling molecule AHL and by cell death using the bacterial toxin CcdB. To evaluate the context dependence of parameters such as the cell growth rate, the carrying capacity, the AHL degradation rate, the leakiness of AHL, the leakiness of toxin CcdB, and the IPTG induction factor, we collect experimental data from the growth control circuit in two different media, at two different pH values, and with several induction levels. We define a set of possible context dependencies that describe how these parameters may differ with the experimental conditions and we develop mathematical models of the growth controller across the different experimental contexts. We then determine whether these parameters are shared across experimental contexts or whether they are context dependent. For each of these possible context dependencies, we use Bayesian inference to assess its plausibility and to estimate the parameters of the growth controller. Ultimately, we find that there is significant experimental context dependence in this circuit. Moreover, we also find that the estimated parameter values are sensitive to our assumption of a context relationship.

Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription Paper
Catanach, Thomas A.0000-0002-4321-3159
Baetica, Ania-Ariadna0000-0003-0421-8181
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-ND 4.0 International license. This project is partially 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. This research was also funded through the John von Neumann Fellowship program at Sandia National Laboratories and used the computational resources of the National Energy Research Scientific Computing Center, a DOE Office of Science User Facility supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. Sandia National Laboratories is a multimission laboratory managed and operated by National Technology & Engineering Solutions of Sandia, LLC, a wholly owned subsidiary of Honeywell International Inc., for the U.S. Department of Energy’s National Nuclear Security Administration under contract DE-NA0003525. SAND no. SAND2018-7077 J.
Funding AgencyGrant Number
Defense Advanced Research Projects Agency (DARPA)HR0011-17-2-0008
Sandia National LaboratoriesUNSPECIFIED
Department of Energy (DOE)DE-AC02-05CH11231
Department of Energy (DOE)DE-NA0003525
Other Numbering System:
Other Numbering System NameOther Numbering System ID
SANDSAND2018-7077 J
Record Number:CaltechAUTHORS:20181008-162020352
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Official Citation:Context Dependence of Biological Circuits Thomas Catanach, Reed D McCardell, Ania-Ariadna Baetica, Richard Murray bioRxiv 360040; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:90175
Deposited By: George Porter
Deposited On:09 Oct 2018 14:43
Last Modified:16 Nov 2021 03:30

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