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Nature. 2011 Jan 13;469(7329):212-5. doi: 10.1038/nature09565. Epub 2010 Dec 8.

Robust multicellular computing using genetically encoded NOR gates and chemical 'wires'.

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

Abstract

Computation underlies the organization of cells into higher-order structures, for example during development or the spatial association of bacteria in a biofilm. 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' devices. 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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PMID:
21150903
[PubMed - indexed for MEDLINE]
PMCID:
PMC3904220
Free PMC Article

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