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

By Alvin Tamsir, Jeffrey J. Tabor, Christopher A. Voigt. Nature, 2010

789 citations recorded by the source corpus.

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.

Subfields: Biomedical Engineering, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/f92e363c45c06c2a9ffb4e465cd656d22a43e72c

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Citations in the corpus

Complex cellular logic computation using ribocomputing devices (2017, neutral): “9 and 10.”
Genomic Mining of Prokaryotic Repressors for Orthogonal Logic Gates (2013, background): “A genetic NOR gate can be built by adding a second input promoter in series to the NOT gate, so that both input promoters drive the expression of the repressor 11 .”
A Comprehensive Survey of Recent Advancements in Molecular Communication (2014, background): “With the prevalence of synthetic biology and applications such as biological computation, simple intercellular communication has been used for multicellular computation [249].”
Biomolecular computing systems: principles, progress and potential (2012, background): “Therefore, most experimental transcriptional circuits use one-or two-input universal gates 30,31,86–90 in parallel and in cascades to increase the total number of inputs (FIG.”