Sources of Variability in a Synthetic Gene Oscillator

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dc.citation.firstpagee1004674
dc.citation.issueNumber12
dc.citation.journalTitlePLoS Computational Biology
dc.citation.volumeNumber11
dc.contributor.authorVeliz-Cuba, Alan
dc.contributor.authorHirning, Andrew J.
dc.contributor.authorAtanas, Adam A.
dc.contributor.authorHussain, Faiza
dc.contributor.authorVancia, Flavia
dc.contributor.authorJosić, Krešimir
dc.contributor.authorBennett, Matthew R.
dc.date.accessioned2016-01-14T20:01:03Z
dc.date.available2016-01-14T20:01:03Z
dc.date.issued2015
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.
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.
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pcbi.1004674
dc.identifier.urihttps://hdl.handle.net/1911/87819
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.titleSources of Variability in a Synthetic Gene Oscillator
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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