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Robust multicellular computing using genetically encoded NOR gates and chemical ‘wires’

Nature volume 469, pages 212215 (13 January 2011) | Download Citation

Abstract

Computation underlies the organization of cells into higher-order structures, for example during development or the spatial association of bacteria in a biofilm1,2,3. Each cell performs a simple computational operation, but when combined with cell–cell communication, intricate patterns emerge. Here we study this process by combining a simple genetic circuit with quorum sensing to produce more complex computations in space. We construct a simple NOR logic gate in Escherichia coli by arranging two tandem promoters that function as inputs to drive the transcription of a repressor. The repressor inactivates a promoter that serves as the output. Individual colonies of E. coli carry the same NOR gate, but the inputs and outputs are wired to different orthogonal quorum-sensing ‘sender’ and ‘receiver’ devices4,5. The quorum molecules form the wires between gates. By arranging the colonies in different spatial configurations, all possible two-input gates are produced, including the difficult XOR and EQUALS functions. The response is strong and robust, with 5- to >300-fold changes between the ‘on’ and ‘off’ states. This work helps elucidate the design rules by which simple logic can be harnessed to produce diverse and complex calculations by rewiring communication between cells.

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Acknowledgements

We thank W. Mulyasasmita and K. Temme for critical discussions. This work was supported by the National Science Foundation (SynBERC, NSF#0943385 and NSF Sandpit CCF-0943385) and the Office of Naval Research.

Author information

Affiliations

  1. Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158, USA

    • Alvin Tamsir
  2. Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, California 94158, USA

    • Jeffrey J. Tabor
    •  & Christopher A. Voigt

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Contributions

A.T. designed and performed the experiments, analysed the data and wrote the manuscript. J.J.T. designed experiments and edited the manuscript. C.A.V. designed experiments, analysed the data and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Christopher A. Voigt.

Supplementary information

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    Supplementary Information

    This file contains Supplementary Figures S1-S11 with legends, Supplementary Table S1-S5, Supplementary Discussions, a List of Strains, Plasmid Maps, and Supplementary References.

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DOI

https://doi.org/10.1038/nature09565

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