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Synchronous long-term oscillations in a synthetic gene circuit.

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Potvin-Trottier, Laurent 
Lord, Nathan D 
Vinnicombe, Glenn 
Paulsson, Johan 


Synthetically engineered genetic circuits can perform a wide variety of tasks but are generally less accurate than natural systems. Here we revisit the first synthetic genetic oscillator, the repressilator, and modify it using principles from stochastic chemistry in single cells. Specifically, we sought to reduce error propagation and information losses, not by adding control loops, but by simply removing existing features. We show that this modification created highly regular and robust oscillations. Furthermore, some streamlined circuits kept 14 generation periods over a range of growth conditions and kept phase for hundreds of generations in single cells, allowing cells in flasks and colonies to oscillate synchronously without any coupling between them. Our results suggest that even the simplest synthetic genetic networks can achieve a precision that rivals natural systems, and emphasize the importance of noise analyses for circuit design in synthetic biology.



Biological Clocks, Escherichia coli, Gene Expression Regulation, Bacterial, Gene Regulatory Networks, Genes, Synthetic, Genetic Engineering, Models, Genetic, Research Design, Synthetic Biology

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Springer Science and Business Media LLC
Some work was performed at the Harvard Medical School Microfluidics Facility and the Center for Nanoscale Systems, a member of the National Nanotechnology Infrastructure Network supported by NSF award ECS-0335765. LPT acknowledges fellowship support from the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Fonds de recherche du Québec – Nature et technologies. This work was supported by NIH Grant GM095784 and NSF Award 1137676.