The Triumphant Return of the Cellular Biosensor

Cell-based biosensors kind of get a bad rap. And the reason for this is pretty simple: cells die. They're delicate little creatures that have to be continually monitored and cared for. And, when used as the basis of a sensing technique, if your cells die, your sensor doesn't work. That's why most sensing schemes use more hearty methods, such as antibodies or synthetic receptors or chemical reactions. This is the reason that I was surprised to see a cell-based sensor grabbing lots of attention in the media recently. In fact, I picked up the story initially from BBC news, but found via a quick internet search that the story had been published on news websites ranging from Science Daily to the India Report.

At any rate, the rationale behind the study was to examine the way in which a popular drug for treatment of schizophrenia works. It is known that the drug causes an increase in production of acetylcholine, but it had also been shown to block the receptors for acetylcholine. Without knowing which dichotomous action was prevailing within the interior of cells, it was impossible to deduce the action of the drug on the brain.

The research team then devised a cell-based biosensor to study the exact effect that the drug had on cells in the brain. The group began with embryonic kidney cells and genetically modified them so that the receptor for acetylcholine was directly coupled with a common G-protein downsteam intracellular signaling cascade. This cascade was then linked to calcium ion upregulation, which activated a calcium-sensitive fluorescent reporter. The fluorescent reporter, then, was fluorescence resonance energy transfer (FRET)-based, meaning that it consisted of two distinct fluorescent molecules. When exposed to calcium, the two fluorescent molecules move closer together, causing one of the molecules to donate more energy to the other, producing a visible color change. This means that when the cells bind acetylcholine, they produce calcium, which causes the color of their fluorescence to shift. When these cells were implanted into rat brains and the rats exposed to the schizophrenia drug, they found no change in the fluorescence of the sensor cells, meaning that the receptor blocking activity of the drug was its primary function.

At least, all this is what I gathered from their most recent publication in Nature. There you can take a look at the team's data as well as a more detailed description of their methods. Really, this is pretty exciting stuff. Utilizing cellular biosensors in this way could be a major player in future drug discovery research. No more guessing as to the function of drugs based on studies on cells in a petri dish. Implant the genetically modified sensor cells, give the rat the drug, and visually see the effect that the drug has on the cells.