Abstract

The choice that bacteria make between sporulation and competence when subjected to stress provides a prototypical example of collective cell fate determination that is stochastic on the individual cell level, yet predictable (deterministic) on the population level. This collective decision is performed by an elaborated gene network. Considerable effort has been devoted to simplify its complexity by taking physics approaches to untangle the basic functional modules that are integrated to form the complete network: (1) A stochastic switch whose transition probability is controlled by two order parameters—population density and internal/external stress. (2) An adaptable timer whose clock rate is normalized by the same two previous order parameters. (3) Sensing units which measure population density and external stress. (4) A communication module that exchanges information about the cells' internal stress levels. (5) An oscillating gate of the stochastic switch which is regulated by the timer. The unique circuit architecture of the gate allows special dynamics and noise management features. The gate opens a window of opportunity in time for competence transitions, during which the circuit generates oscillations that are translated into a chain of short intervals with high transition probability. In addition, the unique architecture of the gate allows filtering of external noise and robustness against variations in circuit parameters and internal noise. We illustrate that a physics approach can be very valuable in investigating the decision process and in identifying its general principles. We also show that both cell-cell variability and noise have important functional roles in the collectively controlled individual decisions.

Highlights

  • Identical cells are capable of stochastically differentiating into various phenotypes with unique attributes

  • The choice that bacteria make between sporulation and competence when subjected to stress provides a prototypical example of collective cell fate determination that is stochastic on the individual cell level, yet predictable on the population level

  • In the subsequent section we introduce how these circuits are interplayed when connected to form the elaborate gene network involved in bacterial decisions between sporulation and competence

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Summary

The physics of bacterial decision making

Eshel Ben-Jacob 1,2,3*, Mingyang Lu 1, Daniel Schultz 4 and Jose’ N. Reviewed by: Avraham Beer, Ben-Gurion University of the Negev, Israel Gurol Suel, University of California, San Diego, USA. The choice that bacteria make between sporulation and competence when subjected to stress provides a prototypical example of collective cell fate determination that is stochastic on the individual cell level, yet predictable (deterministic) on the population level. This collective decision is performed by an elaborated gene network. The unique architecture of the gate allows filtering of external noise and robustness against variations in circuit parameters and internal noise.

INTRODUCTION
REGULATION BY PHOSPHORYLATION
TRANSLATIONAL REGULATION
DYNAMICAL SYSTEM APPROACH TO GENE CIRCUITS
INTEGRATED GENE CIRCUITS
THE STOCHASTIC SWITCH AS A PARTICLE IN A POTENTIAL WELL
GATING OF THE STOCHASTIC SWITCH
THE ADAPTABLE TIMER
THE DECISION GATE
TIME MEASUREMENT BY GENE CIRCUIT
PHOSPHORYLATION DRIVEN REPRESSILATOR
TURNING OSCILLATIONS INTO OPPORTUNITIES
MANAGEMENT OF INTERNAL NOISE
CONCLUSIONS
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