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dc.contributor.authorMacnamara, Cicely Krystyna
dc.contributor.authorChaplain, Mark Andrew Joseph
dc.identifier.citationMacnamara , C K & Chaplain , M A J 2016 , ' Diffusion driven oscillations in gene regulatory networks ' Journal of Theoretical Biology , vol. 407 , pp. 51-70 .
dc.identifier.otherPURE: 244397967
dc.identifier.otherPURE UUID: 160e339a-38f6-4516-90d9-b367f27fff15
dc.identifier.otherScopus: 84979533470
dc.identifier.otherORCID: /0000-0003-4961-6052/work/27162488
dc.identifier.otherORCID: /0000-0001-5727-2160/work/55378857
dc.description.abstractGene regulatory networks (GRNs) play an important role in maintaining cellular function by correctly timing key processes such as cell division and apoptosis. GRNs are known to contain similar structural components, which describe how genes and proteins within a network interact - typically by feedback. In many GRNs, proteins bind to gene-sites in the nucleus thereby altering the transcription rate. If the binding reduces the transcription rate there is a negative feedback leading to oscillatory behaviour in mRNA and protein levels, both spatially (e.g. by observing fluorescently labelled molecules in single cells) and temporally (e.g. by observing protein/mRNA levels over time). Mathematical modelling of GRNs has focussed on such oscillatory behaviour. Recent computational modelling has demonstrated that spatial movement of the molecules is a vital component of GRNs, while it has been proved rigorously that the diffusion coefficient of the protein/mRNA acts as a bifurcation parameter and gives rise to a Hopf-bifurcation. In this paper we consider the spatial aspect further by considering the specific location of gene and protein production, showing that there is an optimum range for the distance between an mRNA gene-site and a protein production site in order to achieve oscillations. We first present a model of a well-known GRN, the Hes1 system, and then extend the approach to examine spatio-temporal models of synthetic GRNs e.g. n-gene repressilator and activator-repressor systems. By incorporating the idea of production sites into such models we show that the spatial component is vital to fully understand GRN dynamics.en
dc.relation.ispartofJournal of Theoretical Biologyen
dc.rights© 2016, Elsevier Ltd. This work is made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at /
dc.subjectHes1 proteinen
dc.subjectSynthetic networksen
dc.subjectActivator-repressor systemsen
dc.subjectSpatial modellingen
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.subjectQA Mathematicsen
dc.subjectQH301 Biologyen
dc.titleDiffusion driven oscillations in gene regulatory networksen
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews. Applied Mathematicsen
dc.description.statusPeer revieweden

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