Last week, researchers from Harvard published a paper with the most gorgeous images I’ve seen in a long time. Now, I work in a microscopy lab, so I see beautiful biological images all the time. These new images of neurons, however, blew me away.
Neurons have been imaged since the 19th century when Santiago Ramon y Cajal first stained brain tissue with silver chromate. This technique (originally used by Camillo Golgi—yes, the guy for whom the organelle is named) enabled only a small percentage of the densely packed neurons to be visible. After observing the stained neurons, Cajal noted that neurons are distinct, polarized cells. Since then, imaging of neurons and the nervous system has improved, and much has been gained from simple observation.
A common technique to visualize cells or subcellular structures is attaching green fluorescent protein (GFP) to a protein of your choice. Originally isolated from jellyfish, GFP is a protein that fluoresces green when exposed to blue light. Proteins of other colors also exist (red, cyan, yellow, orange fluorescent protein, etc.). The researchers at Harvard took advantage of all these fluorescent proteins to create “Brainbow”. Heh. (I love it.)
Now, I’m going to simplify the clever genetics the Harvard researchers pulled off. Don’t yell if you know biology and think I oversimplified. (Let me know if you want a more detailed mechanism—it’s so cool but is complicated unless you’re familiar with genetics.) Remember from ninth grade biology: DNA contains sequences which code for proteins, the so-called workhorses of the cell. Through transcription and translation, information contained in DNA is converted into a sequence of amino acids which comprise proteins. The researchers inserted sequences encoding these fluorescent proteins into the mice genome (in neurons). They then used a certain enzyme that randomly cut out certain fluorescent protein encoding sequences from each cell. What’s left behind was a random assortment of fluorescent protein encoding sequence for each cell. When transcribed and translated, a different assortment of fluorescent proteins appeared in each cell. Further increasing the array of colors, the researchers put a variety of number of copies of each fluorescent protein into the cells. So, some cells had more cyan green fluorescent proteins than yellow fluorescent proteins or vice versa, resulting in a spectrum of blue to green to yellow. In all, 90 colors could be differentiated. Here’s a picture.
Holy shit, right? The neurons almost look artificial, but they’re not. If I snapped those pictures, I’d definitely blow them up and put them up in my apartment.
Overall, a simple concept pulled off by some complicated but elegant genetics. Beautiful stuff.