Let’s say you find an unsightly mole on your arm so you head straight to the dermatologist. After the initial slice of the scalpel, the bunny-rabbit band-aid, and the sugar-free lolly-pop, a few of your cells will be sent off to the lab to see if anything is amiss. DNA may be extracted, its code sequenced to search for the mistake that made the mole.
It’s a laborious process, and it takes time, but a collaborative group of scientists may have found a better way. They describe their finding in a report this month in Nature Nanotechnology. Lead by Professor Christoph Gerber of the Swiss Nano Institute at the University of Basel and Dr. Donata Rimoldi of the Ludwig Institute for Cancer research in Lausanne, the team demonstrates the direct detection of a mutation that causes a protein named BRAF to misbehave.
That mutation is just one tiny typo in the DNA code that gets translated to the message-carrying RNA with the plans for BRAF and finally to BRAF itself. The result is malignant melanoma, mobilized by the now unruly protein that makes your cells grow out-of-control.
To detect the error, the team used an array of micro-cantilevers, originally designed by IBM. Jutting out of a slab of silicon and coated on one side by a thin layer of gold, are eight beams, half of a millimeter long, one-tenth of a millimeter wide, one one-hundredth of a millimeter thick.
The corrupted RNA is attracted to a cantilever pre-treated on the gold top with its specific mate. It will bind tightly to that cantilever, forcing it to bend out of parallel with a control containing a random sequence. Using the difference in the angles that the bent and straight cantilevers reflect laser light, the scientists can tell whether the mutation is present.
The Swiss group could extract the RNA directly from a variety of different cell types, and they can detect the mutation even in the presence of all the other RNA that exists in a cell. If adapted for the clinic, this technology could speed-up the time between cancer discovery and treatment. That means that one day you might be on the correct medication before the band-aid even comes off.
From: F. Huber, H. P. Lang, N. Backmann, D. Rimoldi, and Ch. Gerber, “Direct detection of a BRAF mutation in total RNA from melanoma cells using cantilever arrays,” Nature Nanotechnology, 2013, 8, 125-129, doi:10.1038/nnano.2012.263
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2 thoughts on “Finding the Mutated Needle in an RNA Haystack”
Why or how does the binding of the RNA bend the cantilever?
Great question! To do the experiment, the scientists submerge the cantilevers into a solution of all of the RNA they extract from the cell. RNA likes to be double stranded, just like DNA, so that is how the binding actually works: the RNA goes from single to double stranded.
As for the bending, well the cantilevers are VERY thin, especially with respect to their length and width, and the RNA is only bound on the gold side. The the extra mass of the bound RNA on the top is enough to weigh it down slightly, forcing it to bend.
If you want to see and actually micrograph of the device, Phys.org JUST posted a press release on the study. (What a coinky-dink!)