While most people think about microscopy as involving light and lenses, a new type of microscopy based on DNA sequencing is quickly being developed. DNA microscopy involves knowing the relative positions of individual DNA molecules, due to diffusion and adjacency. Because DNA sequencing technologies are so powerful, giant networks of connections can be generated, allowing images with exquisitely fine structures to be realized. It’s as though a map was created from a set of directions (turn right here, then turn left and go fifty feet), rather than from an overarching view. Alex Boulgakov, a graduate student in Ed Marcotte’s lab, has been working on one such method, which was recently published in a preprint in bioRxiv [1].
“Just imagine I ask you who your neighbors are, and about how far away each of them is. I then go around and ask them who their neighbors are, and so forth. Eventually, I’ll be able to draw a map of your neighborhood just by knowing who is next to whom,” explains Alex.
Although optical microscopy is obviously one of the most fundamental and powerful techniques for biology and other fields, electromagnetic waves are not the only way to see things. Modern biotechnologies allow us to read, write, and manipulate information embodied as DNA. Tagging each molecule in a system with its own unique short piece of DNA gives it a persistent identity, just like a home address. We can then use various biotechnological tricks to ask each tag ‘who is your neighbor?’ and map where everyone is based on the tags. “This can be done even when the sample is not transparent and optics won’t work,” says Alex. “You can’t satellite map something on a cloudy day.”
“Additionally, there are many other things satellites won’t be able to see even on a clear day. It can’t tell me about whether a house has a basement or not, for example. I can, however, ask this when I’m asking who is whose neighbor; then I can have a map of the basements and perhaps a bunch of other molecular properties, too.”
DNA microscopists envision their technologies complementing more traditional microscopies to help tackle outstanding questions such as mapping the brain, where things are not so clear.
[1] Boulgakov, A.A. et al. (2018) From Space to Sequence and Back Again: Iterative DNA Proximity Ligation and its Applications to DNA-Based Imaging. bioRxiv DOI: 10.1101/470211