Complex Biological Computer Commands Living Cells

Researchers have developed a biological computer that functions inside living bacterial cells and tells them what to do, according to a report published today in Nature. Composed of ribonucleic acid, or RNA, the new “ribocomputer” can survive in the bacterium E. coli and respond to a dozen inputs, making it the most complex biological computer to date.

“We’ve developed a way to control how cells behave,” says Alexander Green, an engineer at The Biodesign Institute at Arizona State University, who developed the technology with colleagues at Harvard’s Wyss Institute for Biologically Inspired Engineering. The cells go about their normal business, replicating and sensing what’s going on in their environments, “but they’ve also got this layer of computational machinery that we’ve instructed them to synthesize,” he says.

The biological circuit works just like a digital one: It receives an input and makes a logic-based decision, using AND, OR, and NOT operations. But instead of the inputs and outputs being voltage signals, they are the presence or absence of specific chemicals or proteins.

The process begins with the design of a DNA strand that codes for all the logic the system will need. The researchers insert the synthesized DNA into E. coli bacteria as part of a plasmid—a ring of DNA that can replicate as it floats around in the cell.

The DNA serves as a template for the biological computer’s machinery. The cell’s molecular machinery translates the DNA into RNA, essentially copying the DNA code onto a different molecule for use by the cell. RNA links up with a cell’s ribosome and instructs it to produce a protein specified in the RNA’s code.

Here’s where the system behaves like a computer, rather than just a genetically engineered organism: The RNA only does its job when it receives an input that activates it. That’s because the engineered RNA contains codes not just for a protein, but also for logic functions. The logic portions must receive the right inputs in order to activate the RNA in a way that allows the ribosome to use it to produce the circuit’s output—in this case a protein that glows.

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