My Christmas reading has included a PhD* thesis, I am external examiner for a student at Oxford, and the viva is mid-January. The thesis is on the computer simulations of a model of DNA. The simulations are of what is called DNA origami. Origami is of course folding up a sheet of paper in a precise way, to make a paper plane, paper flower, etc.
DNA origami is folding up a long DNA molecule in a precise way to make a specific shape, such as the triangles shown above. Each of the triangles is maybe a bit less than 100 nanometres across, and consists of one long DNA molecule that forms the overall triangle, with lots of much smaller DNA molecules that ‘staple’ the long and floppy DNA molecule to hold it into a triangular shape. The DNA origami was done by Ilko Bald at Potsdam, and the image was created by Matthias Fenner.
So DNA origami is a lot like paper origami, only you are folding up a linear object (the long floppy DNA molecule), not a sheet and it is around 100 nanometres, or 100 billionths of a metre across, not around 10 cm. DNA origami is fun, you can make tiny little smiley faces from it, and Paul Rothemund, who pioneered the field, did just that.
DNA origami is done in a very different way to paper origami. The triangles, smiley face, etc self-assemble, i.e., you just mix the DNA strands together, and wait. Then with a bit of luck, the structures you want form spontaneously. In our bodies DNA codes for our genes via the sequence of the DNA bases of the four types: A, T, C and G. In DNA origami, the fact that in the DNA double helix bases of type A bind only to T, and C only to G is exploited to staple bits of the long DNA molecule together.
Say to make the origami structure you want, you need to stick part of the scaffold with the sequence ATCCTG, to another part with sequence GGTCAG. You introduce a short staple strand, which has one part with the sequence TAGGAC, and another part with sequence CCAGTC. Then the part of the strand with sequence TAGGAC forms a TAGGAC/ATCCTG double helix with one part of the scaffold, and other part binds to the other part forming a CCAGTC/GGTCAG double helix.
You have then stapled the long DNA molecule together at the desired point. To make a particular shape, you work out which parts of the long DNA strand you need to staple together, add staple DNA strands, and then hope it works. Sometimes it does, but sometimes it doesn’t, and in the experiments they can’t see the DNA strands coming together so when it does not work it is hard to tell why not. The thesis uses computer simulations to look at these strands coming together to try and work in more detail how this origami works.
- Strictly speaking a DPhil thesis as that is what Oxford calls PhDs.