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Sources, propagation and consequences of stochasticity in cellular growth

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Title: Sources, propagation and consequences of stochasticity in cellular growth
Authors: Thomas, P
Terradot, G
Danos, V
Weisse, A
Item Type: Journal Article
Abstract: Growth impacts a range of phenotypic responses. Identifying the sources of growth variation and their propagation across the cellular machinery can thus unravel mechanisms that underpin cell decisions. We present a stochastic cell model linking gene expression, metabolism and replication to predict growth dynamics in single bacterial cells. Alongside we provide a theory to analyse stochastic chemical reactions coupled with cell divisions, enabling efficient parameter estimation, sensitivity analysis and hypothesis testing. The cell model recovers population-averaged data on growth-dependence of bacterial physiology and how growth variations in single cells change across conditions. We identify processes responsible for this variation and reconstruct the propagation of initial fluctuations to growth and other processes. Finally, we study drug-nutrient interactions and find that antibiotics can both enhance and suppress growth heterogeneity. Our results provide a predictive framework to integrate heterogeneous data and draw testable predictions with implications for antibiotic tolerance, evolutionary and synthetic biology.
Issue Date: 30-Oct-2018
Date of Acceptance: 3-Oct-2018
URI: http://hdl.handle.net/10044/1/64557
DOI: https://dx.doi.org/10.1038/s41467-018-06912-9
ISSN: 2041-1723
Publisher: Nature Publishing Group
Journal / Book Title: Nature Communications
Volume: 9
Copyright Statement: © 2018 The Author(s). 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/.
Sponsor/Funder: Royal Commission for the Exhibition of 1851
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
TRANSCRIPTIONAL REGULATORY NETWORK
ESCHERICHIA-COLI
GENE-EXPRESSION
SINGLE-CELL
INHIBITORY CONCENTRATIONS
PHENOTYPIC HETEROGENEITY
NOISE
SIZE
REPLICATION
POPULATION
MD Multidisciplinary
Publication Status: Published
Open Access location: http://dx.doi.org/10.1038/s41467-018-06912-9
Article Number: 4528
Appears in Collections:Mathematics
Department of Medicine
Applied Mathematics and Mathematical Physics
Faculty of Natural Sciences



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