Non-monotonic Response to Monotonic Stimulus: Regulation of Glyoxylate Shunt Gene-Expression Dynamics inﾠ Mycobacterium tuberculosis

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dc.citation.firstpagee1004741
dc.citation.issueNumber2
dc.citation.journalTitlePLoS Computational Biology
dc.citation.volumeNumber12
dc.contributor.authorAscensao, Joao A.
dc.contributor.authorDatta, Pratik
dc.contributor.authorHancioglu, Baris
dc.contributor.authorSontag, Eduardo
dc.contributor.authorGennaro, Maria L.
dc.contributor.authorIgoshin, Oleg A.
dc.contributor.orgCenter for Theoretical Biological Physics
dc.date.accessioned2016-04-04T20:15:21Z
dc.date.available2016-04-04T20:15:21Z
dc.date.issued2016
dc.description.abstractUnderstanding how dynamical responses of biological networks are constrained by underlying network topology is one of the fundamental goals of systems biology. Here we employ monotone systems theory to formulate a theorem stating necessary conditions for non-monotonic time-response of a biochemical network to a monotonic stimulus. We apply this theorem to analyze the non-monotonic dynamics of the σB-regulated glyoxylate shunt gene expression in Mycobacterium tuberculosis cells exposed to hypoxia. We first demonstrate that the known network structure is inconsistent with observed dynamics. To resolve this inconsistency we employ the formulated theorem, modeling simulations and optimization along with follow-up dynamic experimental measurements. We show a requirement for post-translational modulation of σB activity in order to reconcile the network dynamics with its topology. The results of this analysis make testable experimental predictions and demonstrate wider applicability of the developed methodology to a wide class of biological systems.
dc.identifier.citationAscensao, Joao A., Datta, Pratik, Hancioglu, Baris, et al.. "Non-monotonic Response to Monotonic Stimulus: Regulation of Glyoxylate Shunt Gene-Expression Dynamics inﾠ Mycobacterium tuberculosis." <i>PLoS Computational Biology,</i> 12, no. 2 (2016) Public Library of Science: e1004741. http://dx.doi.org/10.1371/journal.pcbi.1004741.
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pcbi.1004741
dc.identifier.urihttps://hdl.handle.net/1911/88836
dc.language.isoeng
dc.publisherPublic Library of Science
dc.rightsThis is an open access article distributed under the terms of the�Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleNon-monotonic Response to Monotonic Stimulus: Regulation of Glyoxylate Shunt Gene-Expression Dynamics inﾠ Mycobacterium tuberculosis
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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