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Published January 20, 2000 | public
Journal Article

A synthetic oscillatory network of transcriptional regulators


Networks of interacting biomolecules carry out many essential functions in living cells, but the 'design principles' underlying the functioning of such intracellular networks remain poorly understood, despite intensive efforts including quantitative analysis of relatively simple systems. Here we present a complementary approach to this problem: the design and construction of a synthetic network to implement a particular function. We used three transcriptional repressor systems that are not part of any natural biological clock to build an oscillating network, termed the repressilator, in Escherichia coli. The network periodically induces the synthesis of green fluorescent protein as a readout of its state in individual cells. The resulting oscillations, with typical periods of hours, are slower than the cell-division cycle, so the state of the oscillator has to be transmitted from generation to generation. This artificial clock displays noisy behaviour, possibly because of stochastic fluctuations of its components. Such 'rational network design' may lead both to the engineering of new cellular behaviours and to an improved understanding of naturally occurring networks.

Additional Information

© 2000 Nature Publishing Group. Received 06 July 1999; Accepted 09 November 1999; Issue Date 20 January 2000. We thank H. Bujard, S. Freundlieb, A. Hochschild, R. Lutz and C. Sternberg for plasmids and advice; U. Alon, N. Barkai, P. Cluzel, L. Frisen, C. Guet, T. Hyman, R. Kishony, A. Jaedicke, P. Lopez, F. Nédélec, S. Pichler, R. Kishony, T. Silhavy, T. Surrey, J. Vilar, C. Wiggins and E. Winfree for discussions; M. Surette for advice and encouragement; L. Hartwell and C. Weitz for comments on the manuscript; and F. Kafatos and E. Karsenti for hospitality and support at the European Molecular Biology Laboratory (EMBL), where part of this work was done. This work was partly supported by the US National Institutes of Health and the von Humboldt Foundation.

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