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The σB alternative sigma factor circuit modulates noise to generate different types of pulsing dynamics.

Published version
Peer-reviewed

Repository DOI


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Authors

Loman, Torkel E 

Abstract

Single-cell approaches are revealing a high degree of heterogeneity, or noise, in gene expression in isogenic bacteria. How gene circuits modulate this noise in gene expression to generate robust output dynamics is unclear. Here we use the Bacillus subtilis alternative sigma factor σB as a model system for understanding the role of noise in generating circuit output dynamics. σB controls the general stress response in B. subtilis and is activated by a range of energy and environmental stresses. Recent single-cell studies have revealed that the circuit can generate two distinct outputs, stochastic pulsing and a single pulse response, but the conditions under which each response is generated are under debate. We implement a stochastic mathematical model of the σB circuit to investigate this and find that the system's core circuit can generate both response types. This is despite one response (stochastic pulsing) being stochastic in nature, and the other (single response pulse) being deterministic. We demonstrate that the main determinant for whichever response is generated is the degree with which the input pathway activates the core circuit, although the noise properties of the input pathway also biases the system towards one or the other type of output. Thus, our work shows how stochastic modelling can reveal the mechanisms behind non-intuitive gene circuit output dynamics.

Description

Acknowledgements: We are grateful for the high performance computing resources provided by the Cambridge Service for Data Driven Discovery. We thank Dr. Katie Abley and Dr Christian Schwall (University of Cambridge) for critical reading of the manuscript.

Keywords

Sigma Factor, Bacterial Proteins, Models, Biological, Stress, Physiological, Bacillus subtilis, Gene Expression Regulation, Bacterial

Journal Title

PLoS Comput Biol

Conference Name

Journal ISSN

1553-734X
1553-7358

Volume Title

19

Publisher

Public Library of Science (PLoS)
Sponsorship
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (721456)