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Gene networks that compensate for crosstalk with crosstalk

Crosstalk is a major challenge to engineering sophisticated synthetic gene networks. A common approach is to insulate signal-transduction pathways by minimizing molecular-level crosstalk between endogenous and synthetic genetic components, but this strategy can be difficult to apply in the context o...

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Autores principales: Müller, Isaak E., Rubens, Jacob R., Jun, Tomi, Graham, Daniel, Xavier, Ramnik, Lu, Timothy K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731275/
https://www.ncbi.nlm.nih.gov/pubmed/31492904
http://dx.doi.org/10.1038/s41467-019-12021-y
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author Müller, Isaak E.
Rubens, Jacob R.
Jun, Tomi
Graham, Daniel
Xavier, Ramnik
Lu, Timothy K.
author_facet Müller, Isaak E.
Rubens, Jacob R.
Jun, Tomi
Graham, Daniel
Xavier, Ramnik
Lu, Timothy K.
author_sort Müller, Isaak E.
collection PubMed
description Crosstalk is a major challenge to engineering sophisticated synthetic gene networks. A common approach is to insulate signal-transduction pathways by minimizing molecular-level crosstalk between endogenous and synthetic genetic components, but this strategy can be difficult to apply in the context of complex, natural gene networks and unknown interactions. Here, we show that synthetic gene networks can be engineered to compensate for crosstalk by integrating pathway signals, rather than by pathway insulation. We demonstrate this principle using reactive oxygen species (ROS)-responsive gene circuits in Escherichia coli that exhibit concentration-dependent crosstalk with non-cognate ROS. We quantitatively map the degree of crosstalk and design gene circuits that introduce compensatory crosstalk at the gene network level. The resulting gene network exhibits reduced crosstalk in the sensing of the two different ROS. Our results suggest that simple network motifs that compensate for pathway crosstalk can be used by biological networks to accurately interpret environmental signals.
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spelling pubmed-67312752019-09-09 Gene networks that compensate for crosstalk with crosstalk Müller, Isaak E. Rubens, Jacob R. Jun, Tomi Graham, Daniel Xavier, Ramnik Lu, Timothy K. Nat Commun Article Crosstalk is a major challenge to engineering sophisticated synthetic gene networks. A common approach is to insulate signal-transduction pathways by minimizing molecular-level crosstalk between endogenous and synthetic genetic components, but this strategy can be difficult to apply in the context of complex, natural gene networks and unknown interactions. Here, we show that synthetic gene networks can be engineered to compensate for crosstalk by integrating pathway signals, rather than by pathway insulation. We demonstrate this principle using reactive oxygen species (ROS)-responsive gene circuits in Escherichia coli that exhibit concentration-dependent crosstalk with non-cognate ROS. We quantitatively map the degree of crosstalk and design gene circuits that introduce compensatory crosstalk at the gene network level. The resulting gene network exhibits reduced crosstalk in the sensing of the two different ROS. Our results suggest that simple network motifs that compensate for pathway crosstalk can be used by biological networks to accurately interpret environmental signals. Nature Publishing Group UK 2019-09-06 /pmc/articles/PMC6731275/ /pubmed/31492904 http://dx.doi.org/10.1038/s41467-019-12021-y Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Müller, Isaak E.
Rubens, Jacob R.
Jun, Tomi
Graham, Daniel
Xavier, Ramnik
Lu, Timothy K.
Gene networks that compensate for crosstalk with crosstalk
title Gene networks that compensate for crosstalk with crosstalk
title_full Gene networks that compensate for crosstalk with crosstalk
title_fullStr Gene networks that compensate for crosstalk with crosstalk
title_full_unstemmed Gene networks that compensate for crosstalk with crosstalk
title_short Gene networks that compensate for crosstalk with crosstalk
title_sort gene networks that compensate for crosstalk with crosstalk
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731275/
https://www.ncbi.nlm.nih.gov/pubmed/31492904
http://dx.doi.org/10.1038/s41467-019-12021-y
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