Mapping Genetic Expression in the Brain

In this TED Talk (which I found via Greg Laden’s Blog), Allan Jones explains how his team is finding out which genes are turned on and off everywhere in the human brain, and making that information freely accessible. My neuroscience bias aside, it’s pretty interesting and novel stuff, so take a peek. If you have a short attention span like me, there’s a cool animation starting at 2:55 that might suck you in more than the preamble does. 

How does this work? He hinted at it, but I don’t think he was perfectly clear, so I’ll fill in the steps to the best of my understanding. As you may know, RNA (specifically messenger RNA, mRNA) is an intermediate step between DNA and proteins, which, simply put, do just about everything in the cell. DNA is transcribed into mRNA, then mRNA is translated into proteins. mRNA is produced when the protein it codes for is needed, so measuring the presence of certain mRNA can tell you what proteins are being made in a cell. This is the point of this line of research.

Firstly, they get a brain from a recently deceased individual, so that the RNA currently in the brain sample does not degrade before they get to it. They dice up the brain using a cryostat and then cut it even more precisely using a laser, mapping the anatomy as they go along. They purify the RNA from this now-tiny sample. This RNA they’ve collected and purified indicates which proteins are being made in the cells in this sample – the problem now is finding out what the RNA molecules they have actually are, what they code for.

To discover this, they attach a fluorescent probe, a little glowing molecule, to all of the RNA. They put this fluorescent RNA sample through a microarray. A microarray is basically a solid surface with up to tens of thousands of tiny areas delineated on it in a grid; each area will have a certain DNA sequence of interest bound to it. They put their RNA sample on the microarray, then wash the contents of the microarray off. If an RNA sequence is complementary to the DNA sequence in a given area, it will stick to that DNA sequence (which is stuck to the microarray) and not wash off – and you can see that it didn’t wash off because it’ll be fluorescent. 

Since you know which DNA is in which area, you can see which of them had complementary RNA in the sample, and therefore know which genes were being expressed (made into proteins) in the original sample. Ta da! By the relative brightness, you can also infer how much RNA there is – how much these genes are being expressed. 

The novelty of this TED Talk is that they’re doing this for every tiny bit of the human brain, and mapping it back onto the brain. He shows this at around 9:36 – in addition to an anatomical map of the brain, they’re making a gene expression map of the brain. 

It seems like this could be very useful in future neuroscience research, and since it’s a free resource it could become very common to refer to this to guide future experimentation. The biggest problem I imagine is the variety between people’s brains. Brains vary quite a bit between people, behaviorally and anatomically, so any map of gene expression is going to be difficult to generalize. I’m sure there are some regions that are more uniform than others though, for which this map can already prove useful even with its tiny sample size. 

If you’re still curious about the magic of microarrays, here‘s the National Center for Biotechnology Information’s primer on them and why they’re very, very important, although their example doesn’t exactly match ours. 

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