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Elucidating effects of reaction rates on dynamics of the lac circuit in Escherichia coli

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

Biosystems, Volume: 175, Pages: 1 - 10

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

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DOI (Published version): 10.1016/j.biosystems.2018.11.003

Abstract

Gene expression is regulated by a complex transcriptional network. It is of interest to quantify uncertainty of not knowing accurately reaction rates of underlying biochemical reactions, and to understand how they affect gene expression. Assuming a kinetic model of the lac circuit in Escherichia col...

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Published in: Biosystems
ISSN: 03032647
Published: 2019
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URI: https://cronfa.swan.ac.uk/Record/cronfa45901
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first_indexed 2018-11-12T20:24:19Z
last_indexed 2019-09-23T14:09:42Z
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spelling 2019-09-23T04:37:11.1347142 v2 45901 2018-11-12 Elucidating effects of reaction rates on dynamics of the lac circuit in Escherichia coli bc7cba9ef306864239b9348c3aea4c3e 0000-0002-2773-2186 Pavel Loskot Pavel Loskot true false 537a2fe031a796a3bde99679ee8c24f5 0000-0002-7715-6914 Paul Rees Paul Rees true false 2018-11-12 EEN Gene expression is regulated by a complex transcriptional network. It is of interest to quantify uncertainty of not knowing accurately reaction rates of underlying biochemical reactions, and to understand how they affect gene expression. Assuming a kinetic model of the lac circuit in Escherichia coli, regardless of how many reactions are involved in transcription regulation, transcription rate is shown to be the most important parameter affecting steady state production of mRNA and protein in the cell. In particular, doubling the transcription rate approximately doubles the number of mRNA synthesized at steady state for any rates of transcription inhibition and activation. On the other hand, increasing the rate of transcription inhibition by 10% reduces the average steady state count of mRNA by about 7%, whereas changes in the rate of transcription activation appear to have no such effect. Furthermore, for wide range of reaction rates in the kinetic model of the lac genetic switch considered, protein production was observed to always reach a maximum before the degradation reduces its count to zero, and this maximum was found to be always at least 27 protein molecules. Such value appears to be a fundamental structural property of genetic circuits making it very robust against changes in the internal and external conditions. Journal Article Biosystems 175 1 10 03032647 Escherichia colilac genetic circuit, steady state synthesis, transcription 31 12 2019 2019-12-31 10.1016/j.biosystems.2018.11.003 COLLEGE NANME Engineering COLLEGE CODE EEN Swansea University 2019-09-23T04:37:11.1347142 2018-11-12T13:06:47.3964110 Faculty of Science and Engineering School of Engineering and Applied Sciences - Biomedical Engineering Komlan Atitey 1 Pavel Loskot 0000-0002-2773-2186 2 Paul Rees 0000-0002-7715-6914 3 0045901-15112018085151.pdf atitey2018(4).pdf 2018-11-15T08:51:51.6970000 Output 1054068 application/pdf Accepted Manuscript true 2019-11-14T00:00:00.0000000 true eng
title Elucidating effects of reaction rates on dynamics of the lac circuit in Escherichia coli
spellingShingle Elucidating effects of reaction rates on dynamics of the lac circuit in Escherichia coli
Pavel Loskot
Paul Rees
title_short Elucidating effects of reaction rates on dynamics of the lac circuit in Escherichia coli
title_full Elucidating effects of reaction rates on dynamics of the lac circuit in Escherichia coli
title_fullStr Elucidating effects of reaction rates on dynamics of the lac circuit in Escherichia coli
title_full_unstemmed Elucidating effects of reaction rates on dynamics of the lac circuit in Escherichia coli
title_sort Elucidating effects of reaction rates on dynamics of the lac circuit in Escherichia coli
author_id_str_mv bc7cba9ef306864239b9348c3aea4c3e
537a2fe031a796a3bde99679ee8c24f5
author_id_fullname_str_mv bc7cba9ef306864239b9348c3aea4c3e_***_Pavel Loskot
537a2fe031a796a3bde99679ee8c24f5_***_Paul Rees
author Pavel Loskot
Paul Rees
author2 Komlan Atitey
Pavel Loskot
Paul Rees
format Journal article
container_title Biosystems
container_volume 175
container_start_page 1
publishDate 2019
institution Swansea University
issn 03032647
doi_str_mv 10.1016/j.biosystems.2018.11.003
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
active_str 0
description Gene expression is regulated by a complex transcriptional network. It is of interest to quantify uncertainty of not knowing accurately reaction rates of underlying biochemical reactions, and to understand how they affect gene expression. Assuming a kinetic model of the lac circuit in Escherichia coli, regardless of how many reactions are involved in transcription regulation, transcription rate is shown to be the most important parameter affecting steady state production of mRNA and protein in the cell. In particular, doubling the transcription rate approximately doubles the number of mRNA synthesized at steady state for any rates of transcription inhibition and activation. On the other hand, increasing the rate of transcription inhibition by 10% reduces the average steady state count of mRNA by about 7%, whereas changes in the rate of transcription activation appear to have no such effect. Furthermore, for wide range of reaction rates in the kinetic model of the lac genetic switch considered, protein production was observed to always reach a maximum before the degradation reduces its count to zero, and this maximum was found to be always at least 27 protein molecules. Such value appears to be a fundamental structural property of genetic circuits making it very robust against changes in the internal and external conditions.
published_date 2019-12-31T03:57:34Z
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score 11.016235

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