Synthetic Biologists Make First Steps Toward Biological Computers

By Joann Fan email: , Feb 13, 2013 05:17 PM EST

Synthetic biology is a field that began more than a decade ago when James Collins, a synthetic biologist at Boston University in Massechusetts developed a genetic 'toggle switch.' He activated the switch in Escherichia coli cells, which are harmless bacteria found in the intestinal tract, and in 2009 he and several others developed a synthetic gene network that could count various user-defined inputs.

This week, Timothy Lu, who worked with Collins in 2009, published a paper in this week's Nature Biotechnology describing the process of altering cells into being able to respond to the 16 binary logic functions (boolean operators such as true, false, and, not, or, etc.). This research takes biology another step closer to electrical engineering, allowing scientists to, someday, encode even more complex computations into cells.

"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," Lu, who led the research, told Nature. He and his team developed 16 plasmids (circular strings of DNA) - one for each of the boolean functions - and inserted them into the E. coli cells.

Each plasmid type has a promoter and terminator DNA sequence, which regulates gene transcription (the first step in gene expression, where a segment of DNA is copied onto RNA), as well as an 'output gene' that triggers the production of a green glowing protein.

You can think of the plasmid as the switch in a logic circuitboard. When certain conditions are fulfilled, it will either transcribe or fail to transcribe the output gene (in this case, green flourescence). "An electric 'AND' gate," which Nature uses as its example, "only gives a positive output when voltage is applied to both inputs." In an electric 'OR' gate, voltage can be applied to either gate, but not both to produce a positive output.

In the genetic version of an 'AND' gate, two terminator sequences between the start and the finish must be neutralized by specific kinds of signal enzymes called recombinase, which can snip and rearrange the controller genes, before the output will be transcribed. For example in the picture below, a 'Recombinase 1' and 'Recombinase 2' would have to alter their respective 'Terminator' genes before the 'Output' gene will activate.

Most importantly, the changes triggered by signal compounds would be permanent. Lu's team found that the altered plasmids will be passed down through at least 90 cell generations, which could give a biologist valuable insight on when something may have happened in a cell's ancestry.

Lu said that in theory, manufacturers could grow cell cultures that can produce drugs when triggered to, or grow cultures whose production can be halted with the introduction of signal compounds.

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