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Biological NOR gates
An artist’s conception shows connections between biologically based CRISPR-dCas9 NOR gates. (University of Washington Graphic)

Researchers from the University of Washington have taken advantage of synthetic biology to turn yeast cells into building blocks for digital information processing.

The experiment, described today in Nature Communications, turned the cells’ genetic code into NOR logic gates suitable for biologically based circuitry.

In digital circuitry that deals with ones and zeros, a NOR gate will produce a “1” output only if both inputs are “0.” To adapt yeast cells for digital processing, the UW team used a gene-editing method called CRISPR-Cas9 to replicate the interactions of ones and zeros with DNA and RNA molecules.

The Cas9 protein served as the molecular gatekeeper in the circuit, determining whether the inputs are ones or zeros based on gene expression, and then activating or deactivating the circuitry accordingly. The output of each circuit was made observable by having the last NOR gate drive the expression of the fluorescent GFP protein.

The researchers assembled up to seven NOR gates into working circuits, with series or parallel connections.

Such synthetic biocircuitry could take in information from environmental sensors and determine the appropriate cellular response.

“While implementing simple programs in cells will never rival the speed or accuracy of computation in silicon, genetic programs can interact with the cell’s environment directly,” senior author Eric Klavins, a UW electrical engineering professor, said in a news release. “For example, reprogrammed cells in a patient could make targeted, therapeutic decisions in the most relevant tissues.”

Theoretically, the technique could be employed to engineer immune cells that can respond to the genetic markers for a specific type of cancer, or produce programmable biosensors capable of diagnosing infectious diseases, or guide a cellular manufacturing process such as biofuel production.

The principal author of the study in Nature Communications, “Digital Logic Circuits in Yeast With CRISPR-dCas9 NOR Gates,” is UW chemical engineering graduate student Miles Gander. Other authors include Justin Vrana, Willy Voje and James Carothers. The research was funded by the Semiconductor Research Corporation and the National Science Foundation.

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