A comprehensive reduced model of the mammalian cell cycle

Almeida, Sofia; Chaves, Madalena; Delaunay, Franck; Feillet, Céline

doi:10.1016/j.ifacol.2017.08.2204

Cited by 6 publications

(15 citation statements)

References 14 publications

(21 reference statements)

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“…To verify that the system's period response to variations of GF is compatible with observations, figure 8 shows entrainment for values of coupling strength c m = 0.2 and c b = 30. The trend of period decrease with GF fits well to data points [11,18] when making a 1 to 1 correspondence GF ¼ %FBS. We chose only the parameters c m and c b and maintained all remaining parameters calibrated as in table 1.…”

Section: The Effect Of Growth Factorsupporting

confidence: 71%

“…Period response of the bidirectional coupled system. Our bidirectional coupling mechanisms are able to reproduce the overall observed oscillators' period response of acceleration with GF and result in a good fit to experimental data[11,18], taking GF ¼ %FBS, with c m = 0.2 and c b = 30. royalsocietypublishing.org/journal/rsos R. Soc. open sci.…”

mentioning

confidence: 59%

“…Original parameters for both models were obtained by nonlinear optimization based on costminimization, with the use of a MATLAB function [18,19]. In order to have oscillation of both systems with periods of the same order of magnitude and consistent with values of experimental observations (namely T clock = 24 h) we scale the original parameters of both models, by multiplying those referring to rates of change by an appropriate constant.…”

Section: Methodsmentioning

confidence: 99%

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Control of synchronization ratios in clock/cell cycle coupling by growth factors and glucocorticoids

2020

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The cell cycle and the circadian clock are essential cyclic cellular processes often synchronous in healthy cells. In this work, we use previously developed mathematical models of the mammalian cell cycle and circadian cellular clock in order to investigate their dynamical interactions. Firstly, we study unidirectional cell cycle → clock coupling by proposing a mechanism of mitosis promoting factor (MPF)-controlled REV-ERB α degradation. Secondly, we analyse a bidirectional coupling configuration, where we add the CLOCK : BMAL1-mediated MPF repression via the WEE1 kinase to the first system. Our simulations reproduce ratios of clock to cell cycle period in agreement with experimental observations and give predictions of the system’s synchronization state response to a variety of control parameters. Specifically, growth factors accelerate the coupled oscillators and dexamethasone (Dex) drives the system from a 1 : 1 to a 3 : 2 synchronization state. Furthermore, simulations of a Dex pulse reveal that certain time regions of pulse application drive the system from 1 : 1 to 3 : 2 synchronization while others have no effect, revealing the existence of a responsive and an irresponsive system’s phase, a result we contextualize with observations on the segregation of Dex-treated cells into two populations.

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Section: The Effect Of Growth Factorsupporting

confidence: 71%

mentioning

confidence: 59%

Section: Methodsmentioning

confidence: 99%

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Control of synchronization ratios in clock/cell cycle coupling by growth factors and glucocorticoids

2020

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“…The cell cycle model was developed and analyzed by Almeida et al 19 and in its most reduced form consists of a two variable system forming a main negative regulatory loop between the essential cell cycle component MPF (mitosis promoting factor), which is the cyclin B/CDK1 complex, necessary and sufficient to carry out the mitotic process, and its repressor the APC:cdc20 complex. This model includes terms describing the action of CDC25 phosphatase, an MPF activator, and the WEE1 kinase, an MPF repressor 19 .…”

Section: Methodsmentioning

confidence: 99%

“…Firstly, we model unidirectional clock → cell cycle coupling via the induction of the MPF repressor wee1 by CLOCK:BMAL1. The action of WEE1 on MPF is included in the term V w 19 . Thus, we multiply this term by the variable BMAL1 to represent the repressor effect of CLOCK:BMAL1.…”

Section: Modeling Coupling Mechanismsmentioning

confidence: 99%

Cell cycle period control through modulation of clock inputs

Almeida

Chaves

Delaunay

2020

J. Bioinform. Comput. Biol.

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In this work, we study period control of the mammalian cell cycle via coupling with the cellular clock. For this, we make use of the oscillators’ synchronization dynamics and investigate methods of slowing down the cell cycle with the use of clock inputs. Clock control of the cell cycle is well established via identified molecular mechanisms, such as the CLOCK:BMAL1-mediated induction of the wee1 gene, resulting in the WEE1 kinase that represses the active form of mitosis promoting factor (MPF), the essential cell cycle component. To investigate the coupling dynamics of these systems, we use previously developed models of the clock and cell cycle oscillators and center our studies on unidirectional clock [Formula: see text] cell cycle coupling. Moreover, we propose an hypothesis of a Growth Factor (GF)-responsive clock, involving a pathway of the non-essential cell cycle complex cyclin D/CDK4. We observe a variety of rational ratios of clock to cell cycle period, such as: 1:1, 3:2, 4:3, and 5:4. Finally, our protocols of period control are successful in effectively slowing down the cell cycle by the use of clock modulating inputs, some of which correspond to existing drugs.

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Computationally modelling cell proliferation: A review

Barbosa

Belinha

Jorge

et al. 2023

Numer Methods Biomed Eng

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Cell proliferation is vital for the development and homeostasis of the human body. For such to occur, cells go through the cell cycle during which they replicate their genetic material and ultimately complete cellular division, when one cell divides into two new cells with equal genetic material. However, if there are some errors or abnormalities during the cell cycle that disrupt the balance between cell death and proliferation, severe problems can occur, such as tumour development, which is currently one of the leading causes of death in the world. Nowadays, mathematical and computational models are used to understand and study several biological mechanisms and processes, namely cellular proliferation. Over the last forty-five years, several models have attempted to describe cell proliferation and its regulation. Due to the complexity of the process, numerous assumptions and simplifications have been considered. This work presents a review of some of these models, focusing mainly on mammalian or generic eukaryotic models. Previously published continuum, discrete and hybrid approaches are presented and compared, in order to understand and highlight the relevance and capabilities of these models, their shortcomings and future challenges.

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A comprehensive reduced model of the mammalian cell cycle

Cited by 6 publications

References 14 publications

Control of synchronization ratios in clock/cell cycle coupling by growth factors and glucocorticoids

Control of synchronization ratios in clock/cell cycle coupling by growth factors and glucocorticoids

Cell cycle period control through modulation of clock inputs

Computationally modelling cell proliferation: A review

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