Coherent activation of a synthetic mammalian gene network |
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| Authors: | Diane M Longo Alexander Hoffmann Lev S Tsimring Jeff Hasty |
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| Institution: | (1) Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA;(2) Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA;(3) BioCircuits Institute, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA;(4) Molecular Biology Section, Division of Biology, Department of Bioengineering, BioCircuits Institute, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; |
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| Abstract: | A quantitative analysis of naturally-occurring regulatory networks, especially those present in mammalian cells, is difficult
due to their high complexity. Much simpler gene networks can be engineered in model organisms and analyzed as isolated regulatory
modules. Recently, several synthetic networks have been constructed in mammalian systems. However, most of these engineered
mammalian networks have been characterized using steady-state population level measurements. Here, we use an integrated experimental-computational
approach to analyze the dynamical response of a synthetic positive feedback network in individual mammalian cells. We observe
a switch-like activation of the network with variable delay times in individual cells. In agreement with a stochastic model
of the network, we find that increasing the strength of the positive feedback results in a decrease in the mean delay time
and a more coherent activation of individual cells. Our results are important for gaining insight into biological processes
which rely on positive feedback regulation. |
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| Keywords: | Gene regulation Positive feedback Signaling dynamics Synthetic gene network |
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