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.
At a glance
- 1951) The General and Logical Theory of Automata (Wiley,
- The chemical basis of morphogenesis. 1953. Bull. Math. Biol. 52, 119–152 (discussion), 153–197 (1990)
- 23–113 (Wolfram Media, 2002) A New Kind of Science
- Engineered bidirectional communication mediates a consensus in a microbial biofilm consortium. Proc. Natl Acad. Sci. USA 104, 17300–17304 (2007) , , &
- A synthetic multicellular system for programmed pattern formation. Nature 434, 1130–1134 (2005) , , , &
- The yeast cell-cycle network is robustly designed. Proc. Natl Acad. Sci. USA 101, 4781–4786 (2004) , , , &
- The bio-logic and machinery of plant morphogenesis. Am. J. Bot. 90, 515–525 (2003)
- Logic-based models for the analysis of cell signaling networks. Biochemistry 49, 3216–3224 (2010) , , &
- Plasticity of the cis-regulatory input function of a gene. PLoS Biol. 4, e45 (2006) , , , &
- Environmental signal integration by a modular AND gate. Mol. Syst. Biol. 3, 133 (2007) , &
- Combinatorial synthesis of genetic networks. Science 296, 1466–1470 (2002) , , &
- A universal RNAi-based logic evaluator that operates in mammalian cells. Nature Biotechnol. 25, 795–801 (2007) et al.
- A synthetic mammalian gene circuit reveals antituberculosis compounds. Proc. Natl Acad. Sci. USA 105, 9994–9998 (2008) et al.
- Diversity-based, model-guided construction of synthetic gene networks with predicted functions. Nature Biotechnol. 27, 465–471 (2009) , &
- Synthesizing a novel genetic sequential logic circuit: a push-on push-off switch. Mol. Syst. Biol. 6, 350 (2010) et al.
- A synthetic genetic edge detection program. Cell 137, 1272–1281 (2009) et al.
- Synthetic gene networks that count. Science 324, 1199–1202 (2009) et al.
- Emergent bistability by a growth-modulating positive feedback circuit. Nature Chem. Biol. 5, 842–848 (2009) , &
- Axiomatization of propositional calculus with Sheffer functors. Notre Dame J. Formal Logic 6, 209–217 (1965)
- Directed evolution of a genetic circuit. Proc. Natl Acad. Sci. USA 99, 16587–16591 (2002) , &
- A mathematical model for transcriptional interference by RNA polymerase traffic in Escherichia coli . J. Mol. Biol. 346, 399–409 (2005) et al.
- Regulation of las and rhl quorum sensing in Pseudomonas aeruginosa. J. Bacteriol. 179, 3127–3132 (1997) , , &
- Signal-amplifying genetic circuit enables in vivo observation of weak promoter activation in the Rhl quorum sensing system. Biotechnol. Bioeng. 89, 709–718 (2005) &
- Gene regulation at the single-cell level. Science 307, 1962–1965 (2005) , , , &
- Noise propagation in gene networks. Science 307, 1965–1969 (2005) &
- 141–146 (Prentice Hall, 1994) & Contemporary Logic Design
- A synchronized quorum of genetic clocks. Nature 463, 326–330 (2010) , , &
- Programming cells: towards an automated ‘genetic compiler’. Curr. Opin. Biotechnol. 21, 572–581 (2010) &
- 1–18 (World Scientific, 2001) Cellular Automata: A Discrete Universe
- Programmable cellular arrays. Int. J. Control 14, 1041–1061 (1971) &
- Supplementary Information (1.6M)
This file contains Supplementary Figures S1-S11 with legends, Supplementary Table S1-S5, Supplementary Discussions, a List of Strains, Plasmid Maps, and Supplementary References.