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dc.contributor.authorVeliz-Cuba, Alan
Hirning, Andrew J.
Atanas, Adam A.
Hussain, Faiza
Vancia, Flavia
Josić, Krešimir
Bennett, Matthew R.
dc.date.accessioned 2016-01-14T20:01:03Z
dc.date.available 2016-01-14T20:01:03Z
dc.date.issued 2015
dc.identifier.citation Veliz-Cuba, Alan, Hirning, Andrew J., Atanas, Adam A., et al.. "Sources of Variability in a Synthetic Gene Oscillator." PLoS Computational Biology, 11, no. 12 (2015) Public Library of Science: e1004674. http://dx.doi.org/10.1371/journal.pcbi.1004674.
dc.identifier.urihttps://hdl.handle.net/1911/87819
dc.description.abstract Synthetic 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.language.iso eng
dc.publisher Public Library of Science
dc.rights This 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.title Sources of Variability in a Synthetic Gene Oscillator
dc.type Journal article
dc.contributor.funder National Institutes of Health
dc.contributor.funder National Science Foundation
dc.contributor.funder Welch Foundation
dc.citation.journalTitle PLoS Computational Biology
dc.citation.volumeNumber 11
dc.citation.issueNumber 12
dc.type.dcmi Text
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pcbi.1004674
dc.identifier.grantID R01GM104974 (National Institutes of Health)
dc.identifier.grantID DMS-1122094 (National Science Foundation)
dc.identifier.grantID C-1729 (Welch Foundation)
dc.type.publication publisher version
dc.citation.firstpage e1004674


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