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

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dc.citation.firstpagee1004741en_US
dc.citation.issueNumber2en_US
dc.citation.journalTitlePLoS Computational Biologyen_US
dc.citation.volumeNumber12en_US
dc.contributor.authorAscensao, Joao A.en_US
dc.contributor.authorDatta, Pratiken_US
dc.contributor.authorHancioglu, Barisen_US
dc.contributor.authorSontag, Eduardoen_US
dc.contributor.authorGennaro, Maria L.en_US
dc.contributor.authorIgoshin, Oleg A.en_US
dc.contributor.orgCenter for Theoretical Biological Physicsen_US
dc.date.accessioned2016-04-04T20:15:21Zen_US
dc.date.available2016-04-04T20:15:21Zen_US
dc.date.issued2016en_US
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.en_US
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.en_US
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pcbi.1004741en_US
dc.identifier.urihttps://hdl.handle.net/1911/88836en_US
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
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.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleNon-monotonic Response to Monotonic Stimulus: Regulation of Glyoxylate Shunt Gene-Expression Dynamics inﾠ Mycobacterium tuberculosisen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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