Logic Gates Built Inside Living Cells

Caltech scientists announced that they had succeeded in building synthetic RNA logic gates inside living cells that actually sense molecules inside the cell.

Several RNA sequences have been identified that bind small molecules, like the drug tetracycline. The authors inserted these into the extended lobes, such that the drug controlled the folding of the RNA. When tetracycline is present, the RNA would fold so that there was no active ribozyme. Remove the tetracycline, and the molecule would reshuffle so that the ribozyme became active.

The end result is that the drug acts as a switch, turning the ribozyme on and off. Making each of the two lobes sensitive to a different drug even created a biological AND switch; both drugs need to be present for an active ribozyme. But a ribozyme isn't necessarily easy to detect, so the authors made it obvious: they inserted their logic gates into a gene that encodes a messenger RNA that produces the Green Fluorescent protein (the protein that recently won folks a Nobel Prize). Now, when the ribozyme is active, the messenger RNA gets broken up and no GFP is made; otherwise, the cells glow green.

This setup allowed the creation of an OR logic system as well.

(Signal Integration Schemes)

This advance could lead to a wide range of applications, since the method would work just as well inside the cells of mammals. Biocomputers in a human bloodstream could control "smart drugs" that activate only under particular circumstances. Sensor cells could be programmed to detect the precursors of diseases like cancer, and then "light up" to alert health care professionals.

SF writer Greg Bear wrote about this idea in his 1984 novel Blood Music; he called them "biologics:"

Why limit oneself to silicon and protein and biochips a hundreth of a millimeter wide, when in almost every living cell there was already a functioning computer with a huge memory?

Let's hope we don't wind up with what Bear called intellectual cells. From RNA-based logic gates compute inside cells.

Scroll down for more stories in the same category. (Story submitted 10/19/2008)

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