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December 08, 2010

UCSF team develops “logic gates” to program bacteria as computers

A team of UCSF researchers has engineered E. coli with the key molecular circuitry that will enable genetic engineers to program cells to communicate and perform computations.

The work builds into cells the same logic gates found in electronic computers and creates a method to create circuits by “rewiring” communications between cells. This system can be harnessed to turn cells into miniature computers

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



That, in turn, will enable cells to be programmed with more intricate functions for a variety of purposes, including agriculture and the production of pharmaceuticals, materials and industrial chemicals, according to Christopher A. Voigt, PhD, a synthetic biologist and associate professor in the UCSF School of Pharmacy’s Department of Pharmaceutical Chemistry who is senior author of the paper.

The most common electronic computers are digital, he explained; that is, they apply logic operations to streams of 1’s and 0’s to produce more complex functions, ultimately producing the software with which most people are familiar. These logic operations are the basis for cellular computation, as well.

“We think of electronic currents as doing computation, but any substrate can act like a computer, including gears, pipes of water, and cells,” Voigt said. “Here, we’ve taken a colony of bacteria that are receiving two chemical signals from their neighbors, and have created the same logic gates that form the basis of silicon computing.”

The Nature paper describes how the Voigt team built simple logic gates out of genes and inserted them into separate E. coli strains. The gate controls the release and sensing of a chemical signal, which allows the gates to be connected among bacteria much the way electrical gates would be on a circuit board.

“The purpose of programming cells is not to have them overtake electronic computers,” explained Voigt, whom Scientist magazine named a “scientist to watch” in 2007 and whose work is included among the Scientist’s Top 10 Innovations of 2009. “Rather, it is to be able to access all of the things that biology can do in a reliable, programmable way.”

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’ 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 up 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

19 pages of supplemental material

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