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Synchronous long-term oscillations in a synthetic gene circuit

Synthetically engineered genetic circuits can perform a wide range of tasks but generally with lower accuracy than natural systems. Here we revisited the first synthetic genetic oscillator, the repressilator(1), and modified it based on principles from stochastic chemistry in single cells. Specifica...

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Autores principales: Potvin-Trottier, Laurent, Lord, Nathan D., Vinnicombe, Glenn, Paulsson, Johan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637407/
https://www.ncbi.nlm.nih.gov/pubmed/27732583
http://dx.doi.org/10.1038/nature19841
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author Potvin-Trottier, Laurent
Lord, Nathan D.
Vinnicombe, Glenn
Paulsson, Johan
author_facet Potvin-Trottier, Laurent
Lord, Nathan D.
Vinnicombe, Glenn
Paulsson, Johan
author_sort Potvin-Trottier, Laurent
collection PubMed
description Synthetically engineered genetic circuits can perform a wide range of tasks but generally with lower accuracy than natural systems. Here we revisited the first synthetic genetic oscillator, the repressilator(1), and modified it based on 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. This created highly regular and robust oscillations. 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 show 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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spelling pubmed-56374072017-10-12 Synchronous long-term oscillations in a synthetic gene circuit Potvin-Trottier, Laurent Lord, Nathan D. Vinnicombe, Glenn Paulsson, Johan Nature Article Synthetically engineered genetic circuits can perform a wide range of tasks but generally with lower accuracy than natural systems. Here we revisited the first synthetic genetic oscillator, the repressilator(1), and modified it based on 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. This created highly regular and robust oscillations. 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 show 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. 2016-10-12 2016-10-27 /pmc/articles/PMC5637407/ /pubmed/27732583 http://dx.doi.org/10.1038/nature19841 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms Reprints and permissions information is available at www.nature.com/reprints.
spellingShingle Article
Potvin-Trottier, Laurent
Lord, Nathan D.
Vinnicombe, Glenn
Paulsson, Johan
Synchronous long-term oscillations in a synthetic gene circuit
title Synchronous long-term oscillations in a synthetic gene circuit
title_full Synchronous long-term oscillations in a synthetic gene circuit
title_fullStr Synchronous long-term oscillations in a synthetic gene circuit
title_full_unstemmed Synchronous long-term oscillations in a synthetic gene circuit
title_short Synchronous long-term oscillations in a synthetic gene circuit
title_sort synchronous long-term oscillations in a synthetic gene circuit
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637407/
https://www.ncbi.nlm.nih.gov/pubmed/27732583
http://dx.doi.org/10.1038/nature19841
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