Thank you for joining us! We look forward to your report on whether it's easier to teach an immunologist DNA origami or a molecular programmer immunology!

The first paper is something to get us in the headspace of the field pre-origami: Directed nucleation assembly of DNA tile complexes for barcode-patterned lattices by Hao Yan et al 🧬

www.pnas.org/doi/10.1073/...

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And that's the story. Extremely nerdy, not particularly flashy, but this little cube was one of the first demonstrations that there is, in fact, Plenty of Room at the Bottom if you have the ingenuity to get matter to self-assemble for you! 8/8

Behold! the final gel! Building the cube up and tearing it down. Lane 4 contains the purified cube. That's cool. Lanes 5-11 are various restriction digests of the cube, which show that it breaks down in ways consistent with it having been a cube with 6 knotted faces in the first place. 7/8

They could prove ligation with exonuclease digestion! Two things in this busy gel:
1. Lane 4 losing the top band meant the cube should be 10 bases-per-side, not 11. This wasn't obvious as DNA has a periodicity of 10.5 bp.
2. Lane 2 keeping the top band from lane 1 means ligation was a success! 6/8

Here's the assembly gel where they add 5 strands to their first, circularized strand and then ligate the two halves of the cube together to get an open 'belt'. However they ran into an aggregation problem in the 6th step, which is why they did the purify-and-reconstitute step from figure 1. 5/8

For modern molecular programmers, ligating the strands looks strange. We almost never do that today! But that was the secret sauce that let them prove they had synthesized a cube with just gels. You see, the ligated DNA strands resulted in knots, which don't fall apart on a denaturing gel. 4/8

But keep in mind! This was a crystallography lab borrowing equipment from the neighboring biochemistry lab, doing something never done before. They didn't have any of the fancy equipment that we take for granted today. No AFM, let alone a CryoEM. So how could they prove they had a cube?? 3/8

Here's the plan: starting with 10 linear, synthetic DNA strands, Ned's team annealed strands onto a growing belt with intermediate ligation steps, resulting in a final structure which has 6 strands, each one corresponding to one face of the cube 2/8