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Effects of growth rate and promoter activity on single-cell protein expression

Protein expression in a single cell depends on its global physiological state. Moreover, genetically-identical cells exhibit variability (noise) in protein expression, arising from the stochastic nature of biochemical processes, cell growth and division. While it is well understood how cellular grow...

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Autores principales: Nordholt, Niclas, van Heerden, Johan, Kort, Remco, Bruggeman, Frank J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524720/
https://www.ncbi.nlm.nih.gov/pubmed/28740089
http://dx.doi.org/10.1038/s41598-017-05871-3
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author Nordholt, Niclas
van Heerden, Johan
Kort, Remco
Bruggeman, Frank J.
author_facet Nordholt, Niclas
van Heerden, Johan
Kort, Remco
Bruggeman, Frank J.
author_sort Nordholt, Niclas
collection PubMed
description Protein expression in a single cell depends on its global physiological state. Moreover, genetically-identical cells exhibit variability (noise) in protein expression, arising from the stochastic nature of biochemical processes, cell growth and division. While it is well understood how cellular growth rate influences mean protein expression, little is known about the relationship between growth rate and noise in protein expression. Here we quantify this relationship in Bacillus subtilis by a novel combination of experiments and theory. We measure the effects of promoter activity and growth rate on the expression of a fluorescent protein in single cells. We disentangle the observed protein expression noise into protein-specific and systemic contributions, using theory and variance decomposition. We find that noise in protein expression depends solely on mean expression levels, regardless of whether expression is set by promoter activity or growth rate, and that noise increases linearly with growth rate. Our results can aid studies of (synthetic) gene circuits of single cells and their condition dependence.
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spelling pubmed-55247202017-07-26 Effects of growth rate and promoter activity on single-cell protein expression Nordholt, Niclas van Heerden, Johan Kort, Remco Bruggeman, Frank J. Sci Rep Article Protein expression in a single cell depends on its global physiological state. Moreover, genetically-identical cells exhibit variability (noise) in protein expression, arising from the stochastic nature of biochemical processes, cell growth and division. While it is well understood how cellular growth rate influences mean protein expression, little is known about the relationship between growth rate and noise in protein expression. Here we quantify this relationship in Bacillus subtilis by a novel combination of experiments and theory. We measure the effects of promoter activity and growth rate on the expression of a fluorescent protein in single cells. We disentangle the observed protein expression noise into protein-specific and systemic contributions, using theory and variance decomposition. We find that noise in protein expression depends solely on mean expression levels, regardless of whether expression is set by promoter activity or growth rate, and that noise increases linearly with growth rate. Our results can aid studies of (synthetic) gene circuits of single cells and their condition dependence. Nature Publishing Group UK 2017-07-24 /pmc/articles/PMC5524720/ /pubmed/28740089 http://dx.doi.org/10.1038/s41598-017-05871-3 Text en © The Author(s) 2017 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
Nordholt, Niclas
van Heerden, Johan
Kort, Remco
Bruggeman, Frank J.
Effects of growth rate and promoter activity on single-cell protein expression
title Effects of growth rate and promoter activity on single-cell protein expression
title_full Effects of growth rate and promoter activity on single-cell protein expression
title_fullStr Effects of growth rate and promoter activity on single-cell protein expression
title_full_unstemmed Effects of growth rate and promoter activity on single-cell protein expression
title_short Effects of growth rate and promoter activity on single-cell protein expression
title_sort effects of growth rate and promoter activity on single-cell protein expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524720/
https://www.ncbi.nlm.nih.gov/pubmed/28740089
http://dx.doi.org/10.1038/s41598-017-05871-3
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