Sources of Variability in a Synthetic Gene Oscillator

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dc.citation.firstpagee1004674en_US
dc.citation.issueNumber12en_US
dc.citation.journalTitlePLoS Computational Biologyen_US
dc.citation.volumeNumber11en_US
dc.contributor.authorVeliz-Cuba, Alanen_US
dc.contributor.authorHirning, Andrew J.en_US
dc.contributor.authorAtanas, Adam A.en_US
dc.contributor.authorHussain, Faizaen_US
dc.contributor.authorVancia, Flaviaen_US
dc.contributor.authorJosić, Krešimiren_US
dc.contributor.authorBennett, Matthew R.en_US
dc.date.accessioned2016-01-14T20:01:03Zen_US
dc.date.available2016-01-14T20:01:03Zen_US
dc.date.issued2015en_US
dc.description.abstractSynthetic gene oscillators are small, engineered genetic circuits that produce periodic variations in target protein expression. Like other gene circuits, synthetic gene oscillators are noisy and exhibit fluctuations in amplitude and period. Understanding the origins of such variability is key to building predictive models that can guide the rational design of synthetic circuits. Here, we developed a method for determining the impact of different sources of noise in genetic oscillators by measuring the variability in oscillation amplitude and correlations between sister cells. We first used a combination of microfluidic devices and time-lapse fluorescence microscopy to track oscillations in cell lineages across many generations. We found that oscillation amplitude exhibited high cell-to-cell variability, while sister cells remained strongly correlated for many minutes after cell division. To understand how such variability arises, we constructed a computational model that identified the impact of various noise sources across the lineage of an initial cell. When each source of noise was appropriately tuned the model reproduced the experimentally observed amplitude variability and correlations, and accurately predicted outcomes under novel experimental conditions. Our combination of computational modeling and time-lapse data analysis provides a general way to examine the sources of variability in dynamic gene circuits.en_US
dc.identifier.citationVeliz-Cuba, Alan, Hirning, Andrew J., Atanas, Adam A., et al.. "Sources of Variability in a Synthetic Gene Oscillator." <i>PLoS Computational Biology,</i> 11, no. 12 (2015) Public Library of Science: e1004674. http://dx.doi.org/10.1371/journal.pcbi.1004674.en_US
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pcbi.1004674en_US
dc.identifier.urihttps://hdl.handle.net/1911/87819en_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.titleSources of Variability in a Synthetic Gene Oscillatoren_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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