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From molecular noise to behavioural variability in a single bacterium

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Abstract

The chemotaxis network that governs the motion of Escherichia coli has long been studied to gain a general understanding of signal transduction. Although this pathway is composed of just a few components, it exhibits some essential characteristics of biological complexity, such as adaptation and response to environmental signals1. In studying intracellular networks, most experiments and mathematical models2,3,4,5 have assumed that network properties can be inferred from population measurements. However, this approach masks underlying temporal fluctuations of intracellular signalling events. We have inferred fundamental properties of the chemotaxis network from a noise analysis of behavioural variations in individual bacteria. Here we show that certain properties established by population measurements, such as adapted states, are not conserved at the single-cell level: for timescales ranging from seconds to several minutes, the behaviour of non-stimulated cells exhibit temporal variations much larger than the expected statistical fluctuations. We find that the signalling network itself causes this noise and identify the molecular events that produce it. Small changes in the concentration of one key network component suppress temporal behavioural variability, suggesting that such variability is a selected property of this adaptive system.

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Figure 1: Schematic view of the apparatus.
Figure 2: Noise of the chemotaxis network.
Figure 3: Behavioural variability as a function of [CheR].
Figure 4: Simulated variability of the chemotaxis network.

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Acknowledgements

P.C. is indebted to S. Leibler in whose laboratory at Princeton University this work was begun. The authors thank J. Doyle for pointing out the existence of the power law in the CCW intervals distributions, H. Park for technical help with Labview software, U. Alon for sharing the expression vector pUA4, J. S. Parkinson for the RP8610 strain and the pRR27 vector, and F. Cattaneo for the use of computers. The authors are thankful to R. Albert, C. Guet, T. Griggs, C. Macal, M. North and R. Rosner for discussions and comments on the manuscript. This work was supported partially by the MRSEC programme of the NSF and the Cancer Research Foundation. T.E. acknowledges support from a joint research funding from the US Department of Energy. T.S.S. acknowledges support from NEDO, Ministry of Economy, Trade and Industry of Japan.

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Author notes

  1. Jose M. G. Vilar

    Present address: Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 307 East 63rd Street, New York, New York, 10021, USA

  2. Thomas S. Shimizu

    Present address: Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts, 02138, USA

  3. Ekaterina Korobkova and Thierry Emonet: These authors contributed equally to this work

Authors and Affiliations

  1. The Institute for Biophysical Dynamics and the James Franck Institute, The University of Chicago, 5640 South Ellis Avenue, Chicago, Illinois, 60637, USA

    Ekaterina Korobkova, Thierry Emonet & Philippe Cluzel

  2. The Rockefeller University, Box 34, 1230 York Avenue, New York, New York, 10021, USA

    Jose M. G. Vilar

  3. Laboratory for Bioinformatics, Institute for Advanced Biosciences, Keio University Fujisawa, 252-8520, Japan

    Thomas S. Shimizu

Authors
  1. Ekaterina Korobkova
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  2. Thierry Emonet
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  3. Jose M. G. Vilar
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  4. Thomas S. Shimizu
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  5. Philippe Cluzel
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Correspondence to Philippe Cluzel.

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The authors declare that they have no competing financial interests.

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Korobkova, E., Emonet, T., Vilar, J. et al. From molecular noise to behavioural variability in a single bacterium. Nature 428, 574–578 (2004). https://doi.org/10.1038/nature02404

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