There's a Pot of Gold at the End of the Brainbow

In the last two years, a new technique has taken the neurobiology world by storm: the Brainbow.
The brainbow is a technique which allows individual neurons in the brain, or sections of the brain, to be mapped by giving them their own special fluorescent colour¹ (see image to the right). It looks pretty, and the technique itself is deceivingly simple.

It takes advantage of something called the Cre/lox system. Cre is an enzyme (a recombinase, to be precise) which will cleave out any DNA that is flanked by sites in DNA with a particular sequence, "lox sites". So if you have Your Favourite Gene (YFG) sandwiched between two lox sites, then Cre will splice YFG out of the DNA. But what if you used two pairs of lox sites? For example, what if you constructed your DNA to look like this:

---lox_A-lox_B--Gene1--lox_A--Gene2--lox_B---

If the lox_A pair is cleaved, then Gene 1 is cut out; if the lox_B pair is cleaved, then Gene 2 is cut out.
The scientists who developed the Brainbow realized that they could use this to make the neurons express one of many different fluorescent proteins. (See image to the left, taken from Nature², click to embiggen) They used nestled lox sites as described above, using multiple fluorescent proteins. The Cre protein is able to cleave a single lox pair, multiple pairs, or no pairs at all. The decision on which pair(s), if any, to cleave is made at random in each cell. What results is a cell that expresses a random colour. If enough colours or colour combinations are Incorporated into the construct, every neuron, in theory, will have its own randomly chosen fluorescent glow. This makes mapping the connections in the brain much easier than ever.

And it makes for pretty artwork too.



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1. Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system, Nature, November 1, 2007.

2. Neuroscience: Making Connections, Nature, 457, 524-527 (2009)

And this year's Nobel in Chemistry goes to...

...Roger Tsien, Martin Chalfie and Osamu Shimomura for their discovery and development of GFP, green fluorescent protein.

Now this is something that really does deserve a Nobel. GFP and its derivatives have really revolutionized molecular biology. Pretty much everyone who does molecular biology has worked with GFP at one point or another. Since its discovery, an entire field of chemistry has opened up, developing new forms of GFP and other fluorescent proteins, that fluoresce different colours. New uses are being found for GFP all the time. GFP, to put it simply, has made a lot of modern molecular biology possible.


These three fellows weren't my picks for the Chemistry prize, but I had seen Tsien's name tossed around on a few sites as a likely winner. Congratulations to the three of them!