Mathematical modelling of p53 signalling during DNA damage response: a survey

Eliaš, J. and Macnamara, C. K. (2021) Mathematical modelling of p53 signalling during DNA damage response: a survey. International Journal of Molecular Sciences, 22(19), 10590. (doi: 10.3390/ijms221910590) (PMID:34638930) (PMCID:PMC8508851)

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Abstract

No gene has garnered more interest than p53 since its discovery over 40 years ago. In the last two decades, thanks to seminal work from Uri Alon and Ghalit Lahav, p53 has defined a truly synergistic topic in the field of mathematical biology, with a rich body of research connecting mathematic endeavour with experimental design and data. In this review we survey and distill the extensive literature of mathematical models of p53. Specifically, we focus on models which seek to reproduce the oscillatory dynamics of p53 in response to DNA damage. We review the standard modelling approaches used in the field categorising them into three types: time delay models, spatial models and coupled negative-positive feedback models, providing sample model equations and simulation results which show clear oscillatory dynamics. We discuss the interplay between mathematics and biology and show how one informs the other; the deep connections between the two disciplines has helped to develop our understanding of this complex gene and paint a picture of its dynamical response. Although yet more is to be elucidated, we offer the current state-of-the-art understanding of p53 response to DNA damage.

Item Type:Articles
Additional Information:This research was funded by the EPSRC grant number EP/N014642/1. The APC was funded by the University of Graz.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Macnamara, Dr Cicely
Authors: Eliaš, J., and Macnamara, C. K.
College/School:College of Science and Engineering > School of Mathematics and Statistics > Mathematics
Journal Name:International Journal of Molecular Sciences
Publisher:MDPI
ISSN:1661-6596
ISSN (Online):1422-0067
Published Online:30 September 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in International Journal of Molecular Sciences 22(19):10590
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172141EPSRC Centre for Multiscale soft tissue mechanics with application to heart & cancerRaymond OgdenEngineering and Physical Sciences Research Council (EPSRC)EP/N014642/1M&S - Mathematics