DNA-based Technologies
for the Next Generation of Precision Biology
We have open positions. Contact us!
Above: A 24-hour post-fertilization zebrafish embryo (right) imaged from the “inside-out”, complete with nucleotide-level genomic detail (each of the 3.8 million points displayed is an individual RNA or DNA molecule). Assembled from a stand-alone volumetric DNA microscopy reaction of specimen on the left (scale bar 200um). From Qian and Weinstein 2023.
Unanticipated technologies can blossom from seemingly unrelated developments. Solid-state quantum theory gave us the transistor; the economics of video-gaming gave us scaling in GPU production which, in turn, precipitated the achievability of modern AI. In 2019, we demonstrated the capacity for the newest generation of DNA sequencing methods to do something qualitatively similar for the way we probe living systems.
Take the following simple example. Let’s say that you want to map the locations of every person on the surface of the earth. There are two ways you can imagine approaching this problem. One is, you can send up a satellite around the earth and take photographs. Two is, you can look at the Bluetooth pings between individuals’ mobile phones. If you record enough of those pings, you can reconstruct everyone’s relative positions without prior knowledge (or a map).
DNA microscopy achieves this for biomolecules, instead of people. In short, in DNA microscopy, rather than using a large apparatus to zero-in on specific locations within the sample, we deploy a massive mix of random, artificial DNA molecules, that give each biomolecule its own unique molecular identity (a molecular IP address).
We then turn these molecules into a massive intercommunicating network that goes to work encoding molecular proximities across the specimen (in cells or tissue) into brand new DNA sequences. Reading these proximities out by high-throughput DNA sequencing, and applying advances in numerical computing, we can infer an image of the original sample (similar to the mobile phone positions in the original example).
In 2019, we demonstrated this for the first time in two-dimensions:
And we are now applying this in three-dimensions to whole, intact organisms (above).
Want to learn more? You can read the 2019 or 2023 paper, watch a seminar, or browse press coverage.