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    Sources of Variability in a Synthetic Gene Oscillator

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    Author
    Veliz-Cuba, Alan; Hirning, Andrew J.; Atanas, Adam A.; Hussain, Faiza; Vancia, Flavia; More... Josić, Krešimir; Bennett, Matthew R. Less...
    Date
    2015
    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.
    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.
    Published Version
    http://dx.doi.org/10.1371/journal.pcbi.1004674
    Type
    Journal article
    Publisher
    Public Library of Science
    Citable link to this page
    https://hdl.handle.net/1911/87819
    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.
    Link to License
    http://creativecommons.org/licenses/by/4.0/
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    • Biochemistry and Cell Biology Publications [118]
    • Bioengineering Publications [632]
    • BioSciences Publications [365]
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    Home | FAQ | Contact Us | Privacy Notice | Accessibility Statement
    Managed by the Digital Scholarship Services at Fondren Library, Rice University
    Physical Address: 6100 Main Street, Houston, Texas 77005
    Mailing Address: MS-44, P.O.BOX 1892, Houston, Texas 77251-1892
    Site Map