Modeling circadian clock–cell cycle interaction effects on cell population growth rates

The circadian clock and the cell cycle are two tightly coupled oscillators. Recent analytical studies have shown counter-intuitive effects of circadian gating of the cell cycle on growth rates of proliferating cells which cannot be explained by a molecular model or a population model alone. In this...

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Main Author: El Khatib, N. (author)
Other Authors: El Cheikh, R. (author), Bernard, S. (author)
Format: article
Published: 2014
Online Access:http://hdl.handle.net/10725/4885
http://dx.doi.org/10.1016/j.jtbi.2014.08.008
http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php
http://www.sciencedirect.com/science/article/pii/S0022519314004561
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author El Khatib, N.
author2 El Cheikh, R.
Bernard, S.
author2_role author
author
author_facet El Khatib, N.
El Cheikh, R.
Bernard, S.
author_role author
dc.creator.none.fl_str_mv El Khatib, N.
El Cheikh, R.
Bernard, S.
dc.date.none.fl_str_mv 2014
2016-12-06T10:58:51Z
2016-12-06T10:58:51Z
2016-12-06
dc.identifier.none.fl_str_mv 0022-5193
http://hdl.handle.net/10725/4885
http://dx.doi.org/10.1016/j.jtbi.2014.08.008
El Cheikh, R., Bernard, S., & El Khatib, N. (2014). Modeling circadian clock–cell cycle interaction effects on cell population growth rates. Journal of theoretical biology, 363, 318-331.
http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php
http://www.sciencedirect.com/science/article/pii/S0022519314004561
dc.language.none.fl_str_mv en
dc.relation.none.fl_str_mv Journal of Theoretical Biology
dc.rights.*.fl_str_mv info:eu-repo/semantics/openAccess
dc.title.none.fl_str_mv Modeling circadian clock–cell cycle interaction effects on cell population growth rates
dc.type.none.fl_str_mv Article
info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/article
description The circadian clock and the cell cycle are two tightly coupled oscillators. Recent analytical studies have shown counter-intuitive effects of circadian gating of the cell cycle on growth rates of proliferating cells which cannot be explained by a molecular model or a population model alone. In this work, we present a combined molecular-population model that studies how coupling the circadian clock to the cell cycle, through the protein WEE1, affects a proliferating cell population. We show that the cell cycle can entrain to the circadian clock with different rational period ratios and characterize multiple domains of entrainment. We show that coupling increases the growth rate for autonomous periods of the cell cycle around 24 h and above 48 h. We study the effect of mutation of circadian genes on the growth rate of cells and show that disruption of the circadian clock can lead to abnormal proliferation. Particularly, we show that Cry 1, Cry 2 mutations decrease the growth rate of cells, Per 2 mutation enhances it and Bmal 1 knockout increases it for autonomous periods of the cell cycle less than 21 h and decreases it elsewhere. Combining a molecular model to a population model offers new insight on the influence of the circadian clock on the growth of a cell population. This can help chronotherapy which takes benefits of physiological rhythms to improve anti-cancer efficacy and tolerance to drugs by administering treatments at a specific time of the day.
eu_rights_str_mv openAccess
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id LAURepo_6ac46d00166496c4e8a3c48eadc54545
identifier_str_mv 0022-5193
El Cheikh, R., Bernard, S., & El Khatib, N. (2014). Modeling circadian clock–cell cycle interaction effects on cell population growth rates. Journal of theoretical biology, 363, 318-331.
language_invalid_str_mv en
network_acronym_str LAURepo
network_name_str Lebanese American University repository
oai_identifier_str oai:laur.lau.edu.lb:10725/4885
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spelling Modeling circadian clock–cell cycle interaction effects on cell population growth ratesEl Khatib, N.El Cheikh, R.Bernard, S.The circadian clock and the cell cycle are two tightly coupled oscillators. Recent analytical studies have shown counter-intuitive effects of circadian gating of the cell cycle on growth rates of proliferating cells which cannot be explained by a molecular model or a population model alone. In this work, we present a combined molecular-population model that studies how coupling the circadian clock to the cell cycle, through the protein WEE1, affects a proliferating cell population. We show that the cell cycle can entrain to the circadian clock with different rational period ratios and characterize multiple domains of entrainment. We show that coupling increases the growth rate for autonomous periods of the cell cycle around 24 h and above 48 h. We study the effect of mutation of circadian genes on the growth rate of cells and show that disruption of the circadian clock can lead to abnormal proliferation. Particularly, we show that Cry 1, Cry 2 mutations decrease the growth rate of cells, Per 2 mutation enhances it and Bmal 1 knockout increases it for autonomous periods of the cell cycle less than 21 h and decreases it elsewhere. Combining a molecular model to a population model offers new insight on the influence of the circadian clock on the growth of a cell population. This can help chronotherapy which takes benefits of physiological rhythms to improve anti-cancer efficacy and tolerance to drugs by administering treatments at a specific time of the day.PublishedN/A2016-12-06T10:58:51Z2016-12-06T10:58:51Z20142016-12-06Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article0022-5193http://hdl.handle.net/10725/4885http://dx.doi.org/10.1016/j.jtbi.2014.08.008El Cheikh, R., Bernard, S., & El Khatib, N. (2014). Modeling circadian clock–cell cycle interaction effects on cell population growth rates. Journal of theoretical biology, 363, 318-331.http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.phphttp://www.sciencedirect.com/science/article/pii/S0022519314004561enJournal of Theoretical Biologyinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/48852021-03-19T10:03:22Z
spellingShingle Modeling circadian clock–cell cycle interaction effects on cell population growth rates
El Khatib, N.
status_str publishedVersion
title Modeling circadian clock–cell cycle interaction effects on cell population growth rates
title_full Modeling circadian clock–cell cycle interaction effects on cell population growth rates
title_fullStr Modeling circadian clock–cell cycle interaction effects on cell population growth rates
title_full_unstemmed Modeling circadian clock–cell cycle interaction effects on cell population growth rates
title_short Modeling circadian clock–cell cycle interaction effects on cell population growth rates
title_sort Modeling circadian clock–cell cycle interaction effects on cell population growth rates
url http://hdl.handle.net/10725/4885
http://dx.doi.org/10.1016/j.jtbi.2014.08.008
http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php
http://www.sciencedirect.com/science/article/pii/S0022519314004561