Journal
NATURE
Volume 538, Issue 7626, Pages 514-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature19841
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Funding
- NSF [ECS-0335765, 1517372]
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- Fonds de recherche du Quebec - Nature et technologies
- National Institutes of Health (NIH) [GM081563, GM095784]
- Division Of Mathematical Sciences
- Direct For Mathematical & Physical Scien [1517372] Funding Source: National Science Foundation
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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(1), 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.
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