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dc.contributor.authorden Breems, N. Y.en
dc.contributor.authorNguyen, L. K.en
dc.contributor.authorKulasiri, Gamalathge D.en
dc.identifier.citationden Breems, N.Y., Nguyen, L.K., & Kulasiri, D. (2014). Integrated signaling pathway and gene expression regulatory model to dissect dynamics of Escherichia coli challenged mammary epithelial cells. Biosystems, 126, 27-40. doi:10.1016/j.biosystems.2014.09.011en
dc.description.abstractCells transform external stimuli, through the activation of signaling pathways, which in turn activate gene regulatory networks, in gene expression. As more omics data are generated from experiments, eliciting the integrated relationship between the external stimuli, the signaling process in the cell and the subsequent gene expression is a major challenge in systems biology. The complex system of non-linear dynamic protein interactions in signaling pathways and gene networks regulates gene expression. The complexity and non-linear aspects have resulted in the study of the signaling pathway or the gene network regulation in isolation. However, this limits the analysis of the interaction between the two components and the identification of the source of the mechanism differentiating the gene expression profiles. Here, we present a study of a model of the combined signaling pathway and gene network to highlight the importance of integrated modeling. Based on the experimental findings we developed a compartmental model and conducted several simulation experiments. The model simulates the mRNA expression of three different cytokines (RANTES, IL8 and TNFα) regulated by the transcription factor NFkB in mammary epithelial cells challenged with E. coli. The analysis of the gene network regulation identifies a lack of robustness and therefore sensitivity for the transcription factor regulation. However, analysis of the integrated signaling and gene network regulation model reveals distinctly different underlying mechanisms in the signaling pathway responsible for the variation between the three cytokine's mRNA expression levels. Our key findings reveal the importance of integrating the signaling pathway and gene expression dynamics in modeling. Modeling infers valid research questions which need to be verified experimentally and can assist in the design of future biological experiments.en
dc.publisherElsevier Irelanden
dc.relationThe original publication is available from - Elsevier Ireland -
dc.subjectintegrated networken
dc.subjectsignaling pathwayen
dc.subjectgene regulatory networken
dc.subjectNF kappa Ben
dc.subject.meshMammary Glands, Animalen
dc.subject.meshEpithelial Cellsen
dc.subject.meshEscherichia colien
dc.subject.meshSignal Transductionen
dc.subject.meshGene Expression Regulationen
dc.subject.meshGene Regulatory Networksen
dc.titleIntegrated signaling pathway and gene expression regulatory model to dissect dynamics of Escherichia coli challenged mammary epithelial cellsen
dc.typeJournal Article
lu.contributor.unitLincoln Universityen
lu.contributor.unitFaculty of Agriculture and Life Sciencesen
lu.contributor.unitDepartment of Wine, Food and Molecular Biosciencesen
dc.subject.anzsrc11 Medical and Health Sciencesen
dc.subject.anzsrc060102 Bioinformaticsen
dc.subject.anzsrc100499 Medical Biotechnology not elsewhere classifieden
dc.subject.anzsrc1004 Medical Biotechnologyen
dc.subject.anzsrc06 Biological Sciencesen
dc.subject.anzsrc09 Engineeringen
pubs.notespublisher: Elsevier articletitle: Integrated signaling pathway and gene expression regulatory model to dissect dynamics of Escherichia coli challenged mammary epithelial cells journaltitle: Biosystems articlelink: content_type: article copyright: Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.en
pubs.organisational-group/LU/Agriculture and Life Sciences
pubs.organisational-group/LU/Agriculture and Life Sciences/WFMB
pubs.organisational-group/LU/Research Management Office
pubs.organisational-group/LU/Research Management Office/2018 PBRF Staff group

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