1. Computational and Systems Biology
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Phenotypic diversity and temporal variability in a bacterial signaling network revealed by single-cell FRET

  1. Johannes M Keegstra
  2. Keita Kamino
  3. François Anquez
  4. Milena D Lazova
  5. Thierry Emonet
  6. Thomas S Shimizu Is a corresponding author
  1. AMOLF Institute, Netherlands
  2. Yale University, United States
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Cite as: eLife 2017;6:e27455 doi: 10.7554/eLife.27455

Abstract

We present in vivo single-cell FRET measurements in the Escherichia coli chemotaxis system that reveal pervasive signaling variability, both across cells in isogenic populations and within individual cells over time. We quantify cell-to-cell variability of adaptation, ligand response, as well as steady-state output level, and analyze the role of network design in shaping this diversity from gene expression noise. In the absence of changes in gene expression, we find that single cells demonstrate strong temporal fluctuations. We provide evidence that such signaling noise can arise from at least two sources: (i) stochastic activities of adaptation enzymes, and (ii) receptor-kinase dynamics in the absence of adaptation. We demonstrate that under certain conditions, (ii) can generate giant fluctuations that drive signaling activity of the entire cell into a stochastic two-state switching regime. Our findings underscore the importance of molecular noise, arising not only in gene expression but also in protein networks.

Article and author information

Author details

  1. Johannes M Keegstra

    AMOLF Institute, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0002-8877-4881
  2. Keita Kamino

    AMOLF Institute, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  3. François Anquez

    AMOLF Institute, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  4. Milena D Lazova

    AMOLF Institute, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. Thierry Emonet

    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0002-6746-6564
  6. Thomas S Shimizu

    AMOLF Institute, Amsterdam, Netherlands
    For correspondence
    shimizu@amolf.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0003-0040-7380

Funding

Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO Vidi 680-47-515)

  • Thomas S Shimizu

Stichting voor Fundamenteel Onderzoek der Materie (FOM Projectruimte 11PR2958)

  • Thomas S Shimizu

Paul G. Allen Family Foundation (11562)

  • Thierry Emonet
  • Thomas S Shimizu

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Naama Barkai, Reviewing Editor, Weizmann Institute of Science, Israel

Publication history

  1. Received: April 4, 2017
  2. Accepted: November 17, 2017
  3. Accepted Manuscript published: December 12, 2017 (version 1)
  4. Accepted Manuscript updated: December 14, 2017 (version 2)

Copyright

© 2017, Keegstra et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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