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Deterministic and stochastic population-level simulations of an artificial lac operon genetic network

Stamatakis, M; Zygourakis, K; (2011) Deterministic and stochastic population-level simulations of an artificial lac operon genetic network. BMC Bioinformatics , 12 , Article 301. 10.1186/1471-2105-12-301. Green open access

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Abstract

Background: The lac operon genetic switch is considered as a paradigm of genetic regulation. This system has a positive feedback loop due to the LacY permease boosting its own production by the facilitated transport of inducer into the cell and the subsequent de-repression of the lac operon genes. Previously, we have investigated the effect of stochasticity in an artificial lac operon network at the single cell level by comparing corresponding deterministic and stochastic kinetic models.Results: This work focuses on the dynamics of cell populations by incorporating the above kinetic scheme into two Monte Carlo (MC) simulation frameworks. The first MC framework assumes stochastic reaction occurrence, accounts for stochastic DNA duplication, division and partitioning and tracks all daughter cells to obtain the statistics of the entire cell population. In order to better understand how stochastic effects shape cell population distributions, we develop a second framework that assumes deterministic reaction dynamics. By comparing the predictions of the two frameworks, we conclude that stochasticity can create or destroy bimodality, and may enhance phenotypic heterogeneity.Conclusions: Our results show how various sources of stochasticity act in synergy with the positive feedback architecture, thereby shaping the behavior at the cell population level. Further, the insights obtained from the present study allow us to construct simpler and less computationally intensive models that can closely approximate the dynamics of heterogeneous cell populations. © 2011 Stamatakis and Zygourakis; licensee BioMed Central Ltd.

Type: Article
Title: Deterministic and stochastic population-level simulations of an artificial lac operon genetic network
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/1471-2105-12-301
Publisher version: http://dx.doi.org/10.1186/1471-2105-12-301
Language: English
Additional information: © 2011 Stamatakis and Zygourakis; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Chemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/1356181
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