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Determining the Transcription Rates Yielding Steady-State Production of mRNA in the Lac Genetic Switch of Escherichia coli

Paul Rees Orcid Logo, Komlan Atitey, Pavel Loskot Orcid Logo, Paul Rees

Journal of Computational Biology

Swansea University Authors: Paul Rees Orcid Logo, Pavel Loskot Orcid Logo

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DOI (Published version): 10.1089/cmb.2018.0055

Abstract

To elucidate the regulatory dynamics of the gene expression activation and inactivation, an in silico biochemical model of the lac circuit in Escherichia coli was used to evaluate the transcription rates that yield the steady-state mRNA production in active and inactive states of the lac circuit. Th...

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Published in: Journal of Computational Biology
ISSN: 1557-8666
Published: 2018
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URI: https://cronfa.swan.ac.uk/Record/cronfa40085
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spelling 2019-03-26T17:41:05.8715362 v2 40085 2018-05-10 Determining the Transcription Rates Yielding Steady-State Production of mRNA in the Lac Genetic Switch of Escherichia coli 537a2fe031a796a3bde99679ee8c24f5 0000-0002-7715-6914 Paul Rees Paul Rees true false bc7cba9ef306864239b9348c3aea4c3e 0000-0002-2773-2186 Pavel Loskot Pavel Loskot true false 2018-05-10 MEDE To elucidate the regulatory dynamics of the gene expression activation and inactivation, an in silico biochemical model of the lac circuit in Escherichia coli was used to evaluate the transcription rates that yield the steady-state mRNA production in active and inactive states of the lac circuit. This result can be used in synthetic biology applications to understand the limits of the genetic synthesis. Since most genetic networks involve many interconnected components with positive and negative feedback control, intuitive understanding of their dynamics is often difficult to obtain. Although the kinetic model of the lac circuit considered involves only a single positive feedback, the developed computational framework can be used to evaluate supported ranges of other reaction rates in genetic circuits with more complex regulatory networks. More specifically, the inducible lac gene switch in E. coli is regulated by unbinding and binding of the inducer-repressor complexes to or from the DNA operator to switch the gene expression on and off. The dependency of mRNA production at steady state on different transcription rates and the repressor complexes has been studied by computer simulations in the Lattice Microbe software. Provided that the lac circuit is in active state, the transcription rate is independent of the inducer-repressor complexes present in the cell. In inactive state, the transcription rate is dependent on the specific inducer-repressor complex bound to the operator that inactivates the gene expression. We found that the repressor complex with the largest affinity to the operator yields the smallest range of the feasible transcription rates to yield the steady state while the lac circuit is in inactive state. In contrast, the steady state in active state can be obtained for any value of the transcription rate. Journal Article Journal of Computational Biology 1557-8666 Escherichia coli; kinetic model; mRNA; steady state; transcription 31 12 2018 2018-12-31 10.1089/cmb.2018.0055 COLLEGE NANME Biomedical Engineering COLLEGE CODE MEDE Swansea University 2019-03-26T17:41:05.8715362 2018-05-10T09:52:11.3416409 Faculty of Science and Engineering School of Engineering and Applied Sciences - Biomedical Engineering Paul Rees 0000-0002-7715-6914 1 Komlan Atitey 2 Pavel Loskot 0000-0002-2773-2186 3 Paul Rees 4 0040085-10052018095433.pdf atitey2018.pdf 2018-05-10T09:54:33.4900000 Output 1345117 application/pdf Accepted Manuscript true 2019-06-29T00:00:00.0000000 true eng
title Determining the Transcription Rates Yielding Steady-State Production of mRNA in the Lac Genetic Switch of Escherichia coli
spellingShingle Determining the Transcription Rates Yielding Steady-State Production of mRNA in the Lac Genetic Switch of Escherichia coli
Paul Rees
Pavel Loskot
title_short Determining the Transcription Rates Yielding Steady-State Production of mRNA in the Lac Genetic Switch of Escherichia coli
title_full Determining the Transcription Rates Yielding Steady-State Production of mRNA in the Lac Genetic Switch of Escherichia coli
title_fullStr Determining the Transcription Rates Yielding Steady-State Production of mRNA in the Lac Genetic Switch of Escherichia coli
title_full_unstemmed Determining the Transcription Rates Yielding Steady-State Production of mRNA in the Lac Genetic Switch of Escherichia coli
title_sort Determining the Transcription Rates Yielding Steady-State Production of mRNA in the Lac Genetic Switch of Escherichia coli
author_id_str_mv 537a2fe031a796a3bde99679ee8c24f5
bc7cba9ef306864239b9348c3aea4c3e
author_id_fullname_str_mv 537a2fe031a796a3bde99679ee8c24f5_***_Paul Rees
bc7cba9ef306864239b9348c3aea4c3e_***_Pavel Loskot
author Paul Rees
Pavel Loskot
author2 Paul Rees
Komlan Atitey
Pavel Loskot
Paul Rees
format Journal article
container_title Journal of Computational Biology
publishDate 2018
institution Swansea University
issn 1557-8666
doi_str_mv 10.1089/cmb.2018.0055
college_str Faculty of Science and Engineering
hierarchytype
hierarchy_top_id facultyofscienceandengineering
hierarchy_top_title Faculty of Science and Engineering
hierarchy_parent_id facultyofscienceandengineering
hierarchy_parent_title Faculty of Science and Engineering
department_str School of Engineering and Applied Sciences - Biomedical Engineering{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Engineering and Applied Sciences - Biomedical Engineering
document_store_str 1
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description To elucidate the regulatory dynamics of the gene expression activation and inactivation, an in silico biochemical model of the lac circuit in Escherichia coli was used to evaluate the transcription rates that yield the steady-state mRNA production in active and inactive states of the lac circuit. This result can be used in synthetic biology applications to understand the limits of the genetic synthesis. Since most genetic networks involve many interconnected components with positive and negative feedback control, intuitive understanding of their dynamics is often difficult to obtain. Although the kinetic model of the lac circuit considered involves only a single positive feedback, the developed computational framework can be used to evaluate supported ranges of other reaction rates in genetic circuits with more complex regulatory networks. More specifically, the inducible lac gene switch in E. coli is regulated by unbinding and binding of the inducer-repressor complexes to or from the DNA operator to switch the gene expression on and off. The dependency of mRNA production at steady state on different transcription rates and the repressor complexes has been studied by computer simulations in the Lattice Microbe software. Provided that the lac circuit is in active state, the transcription rate is independent of the inducer-repressor complexes present in the cell. In inactive state, the transcription rate is dependent on the specific inducer-repressor complex bound to the operator that inactivates the gene expression. We found that the repressor complex with the largest affinity to the operator yields the smallest range of the feasible transcription rates to yield the steady state while the lac circuit is in inactive state. In contrast, the steady state in active state can be obtained for any value of the transcription rate.
published_date 2018-12-31T03:51:00Z
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score 11.035634

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