I hope my liveblog of DNA 19 was amusing. There were a lot of great talks. People seemed to think mine was interesting. I have to say that Peng Yin and the members of his group stole the show a bit. DNA bricks and the superresolution microscopy were really beautiful, plus he is involved in the RNAi applications (with Niles Pierce and others) which are very exciting. I think that was absolutely incredible. But the nanopore was probably my favorite structure (from the Simmel lab). All in all, I learned a lot and was very grateful to participate.
Kurt Gothelf showed how DNA can be used to assemble polymers. I usually think of polymerization reactions as being very random. I thought it was interesting that he can define a path across the surface of a DNA origami tile to make a directed polymer chain. The shape and structure are both controlled. These polymers also bind carbon nanotubes, so now you can put carbon nanotuves along defined paths? That sounds promising.
Tim Liedl talked about engineering metamaterials with DNA. Metamaterials have behavior that depends on their structure rather than their composition. Gold nanoparticles are very different than solid gold. They are arranging the gold/metal nanoparticles by using DNA. I lost the thread of the novelty of this material. I do remember when this group published a paper using gold nanoparticle-decorated DNA to control the chirality and optical activity of structures. They could make the little spiral gold structures rotate polarized light left or right depending on how they assembled it.
Friedrich Simmel showed recent work in functional nanochannels produced using hydrophobically-modified DNA. They are big and leaky but they work! They insert themselves into a membrane and make a big channel. Simmel also talked about hydrophobic folding of origami. That is really interesting from a protein folding perspective. It is not programmable like base-pairing, but it is orthogonal to base pairing and might be versatile in other contextx. They also made droplets and put a chemical reaction network oscillator inside. Evidently, sometimes, small droplets can oscillate but not larger ones. I would like to explore why that is in more detail. It certainly looks great.
Ned Seeman. Everyone in the field knows Ned Seeman’s contribution. The great vision was to use hexamer scaffolds extending in wide, repeating units to stabilize other crystals. He put the kibosh on that. It turns out that almost everything you might include in such a network destabilized it. But it did end up working and it did make some neat structures. Really, the Seeman group pioneered the structural DNA design idea. He also talked about Alex Rich in 1956 inventing hybridization, of which I had no prior knowledge.
John Spence talked about how X-ray lasers can be used for structural and dynamic biology. The system takes destructive snapshots and averages them (since each snapshot uses so much X-ray radiation that the molecules are destroyed in the process). Nonetheless, this can build up an average picture. If you do pulse-delay experiments, you can get a time-resolved movie of a molecular process. Very cool.
Yannick Rondelez explained his DNA toolbox. He uses enzymes; enzymes are rare at this conference. Polymerase and nickase can create a cycle of production of copies of a template. The copies can go on to prime other copying processes (including self-copying) and it can inhibit other copying processes. That’s a nice system for building reaction networks. That’s the toolbox. The computer takes target behavior, translates to a network, then to reactions, then to DNA.
What kinds of dynamic reaction systems can you make? You can make bistable, autoamplifying, cyclical, etc. What is really amazing is that you can evolve a reaction network in silico using a genetic algorithm! Then, you can make the stuff and show that a bizarre reaction network (like a square wave oscillator!). I gather he has not yet actually produced the square wave experimentally. It’s only 18 nucleotides, but hybridization/reaction rates need to be super-precisely defined, I expect. Then use a microfluidic droplet-based parameter space screening chip. That’s almost as good as an in vitro square wave oscillator.
Hendrik Dietz: ATP synthase is a nanofactory. Look at that enzyme. As enzymes go, it’s huge. The vast number of ATP synthase molecules in a human body make 50 lbs of ATP every day. They are in the middle of the gap in the humans’ ability to engineer matter: At 20 nm, they are too small for photolithography (computer chip manufacturing). Yet they are also too big for synthetic chemistry. DNA origami is about the only tool we have to precisely engineer things at this scale. The detailed principles of protein folding, even of 50 year old protein structures, are still unknown. Could we be close with DNA origami to making functional structures?
The Dietz lab made a completely asymmetric structure at about 20 nm. TEM tomography shows its shape is accurate to the design. It is made of about 440,000 atoms. For a molecule, it is very, very big. Prof. Dietz had a 3D printed model to compare to a 3D printed ribosome. The designed molecule is significantly bigger.