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Spatial-stochastic modelling of synthetic gene regulatory networks

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jtb2019.pdf (2.989Mb)
Date
07/05/2019
Author
Macnamara, Cicely K.
Mitchell, Elaine
Chaplain, Mark A. J.
Keywords
Synthetic gene regulatory networks
Repressilators
Activator-repressor systems
Spatial modelling
QA75 Electronic computers. Computer science
QH301 Biology
RC0254 Neoplasms. Tumors. Oncology (including Cancer)
DAS
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Abstract
Transcription factors are important molecules which control the levels of mRNA and proteins within cells by modulating the process of transcription (the mechanism by which mRNA is produced within cells) and hence translation (the mechanism by which proteins are produced within cells). Transcription factors are part of a wider family of molecular interaction networks known as gene regulatory networks (GRNs) which play an important role in key cellular processes such as cell division and apoptosis (e.g. the p53-Mdm2, NFκB pathways). Transcription factors exert control over molecular levels through feedback mechanisms, with proteins binding to gene sites in the nucleus and either up-regulating or down-regulating production of mRNA. In many GRNs, there is a negative feedback in the network and the transcription rate is reduced. Typically, this leads to the mRNA and protein levels oscillating over time and also spatially between the nucleus and cytoplasm. When experimental data for such systems is analysed, it is observed to be noisy and in many cases the actual numbers of molecules involved are quite low. In order to model such systems accurately and connect with the data in a quantitative way, it is therefore necessary to adopt a stochastic approach as well as take into account the spatial aspect of the problem. In this paper, we extend previous work in the area by formulating and analysing stochastic spatio-temporal models of synthetic GRNs e.g. repressilators and activator-repressor systems.
Citation
Macnamara , C K , Mitchell , E & Chaplain , M A J 2019 , ' Spatial-stochastic modelling of synthetic gene regulatory networks ' , Journal of Theoretical Biology , vol. 468 , pp. 27-44 . https://doi.org/10.1016/j.jtbi.2019.02.003
Publication
Journal of Theoretical Biology
Status
Peer reviewed
DOI
https://doi.org/10.1016/j.jtbi.2019.02.003
ISSN
0022-5193
Type
Journal article
Rights
Copyright © 2019 Elsevier Ltd. All rights reserved. This work has been 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 https://doi.org/10.1016/j.jtbi.2019.02.003
Description
Funding: EPSRC Grant No. EP/N014642/1 (EPSRC Centre for Multiscale Soft Tissue Mechanics - With Application to Heart & Cancer) (MAJC,CKM).
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/19433

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