Synthetic DNA can perform logic operations such as NAND and give out the answer by lighting up the cell with green fluorescent protein, or GFP.

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Synthetic biologists have developed DNA modules that perform logic operations in living cells. These genetic circuits could be used to track key moments in a cells life or, at the flick of a chemical switch, change a cells fate, the researchers say. Their results are described this week in Nature Biotechnology1.

Synthetic biology seeks to bring concepts from electronic engineering to cell biology, treating gene functions as components in a circuit. To that end, researchers at the Massachusetts Institute of Technology (MIT) in Cambridge have devised a set of simple genetic modules that respond to inputs much like the Boolean logic gates used in computers.

These developments will more readily enable one to create programmable cells with decision-making capabilities for a variety of applications, says James Collins, a synthetic biologist at Boston University in Massachusetts who was not involved in the study.

Collins developed the genetic toggle switch that helped to kick-start the field of synthetic biology more than a decade ago2. A wide range of computational circuits for cells have been developed since, including a simple counter that Collins and his team devised in 20093.

But to make this a really rigorous engineering discipline, we need to move towards frameworks that allow you to program cells in a more scalable fashion, says Timothy Lu, a synthetic biologist at MIT who led the latest research. We wanted to show you can assemble a bunch of simple parts in a very easy fashion to give you many types of logical functions.

Lus logic modules are based on plasmids, circular strings of DNA, that are inserted into Escherichia coli cells. He and his colleagues devised 16 plasmids one for each of the binary logic functions allowable in computation. Each variant comprises promoter and terminator DNA sequences, which start or halt gene transcription, and an output gene that encodes a green fluorescent protein.

The key to the system is the use of recombinase enzymes, which cut and rearrange promoter and terminator DNA sequences to turn them on or off. In other words, recombinase enzymes are the inputs that determine whether the output gene is transcribed.

An electronic AND gate, for example, gives a positive output only when voltage is applied to both of its inputs. In the genetic version, the output gene is transcribed only when both terminator sequences between it and the promoter sequence are neutralized by two inputs in the form of recombinase enzymes.

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How to turn living cells into computers

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