Scheme: Wolfson Research Merit Awards
Organisation: University of Oxford
Dates: Apr 2012-Mar 2017
Summary: Natural DNA stores information in the sequence in which the bases A,C,G,T are linked together: we use this information storage capacity to control interactions between strands of DNA through sequence design. We use this control to make nanometre-scale structures and synthetic molecular machinery by self-assembly. If we wish two strands to bind together to form a stable double helix, we simply have to obey the rules ‘A pairs with T, C with G’. If we also deliberately weaken undesired interactions, our target structure – which could be a cage or molecular machine – will be much more stable than any other possible product and is likely to assemble spontaneously when the component DNA strands are mixed. Sometimes the assembly process gets stuck in what is known as a ‘kinetic trap’ – although our target structure is the most stable, the system never progresses beyond intermediate structures that are stable enough to be locked in place. We are studying what goes wrong with assembly, and how to avoid these traps.
The following are examples of what we can do when assembly works well.
1 We make molecular robots that navigate networks of DNA tracks. We use similar robots to pick up chemical building blocks and add them, in sequence, to form a polymer.
2 We have shown that DNA cages can encapsulate protein molecules, can enter cells, and can be opened by molecular signals. We are investigating their use as smart drug delivery vehicles.
3 We have created artificial protein crystals by binding protein molecules to a regular DNA lattice. This technique may help to determine the molecular structures of proteins and thus facilitate drug design.
It is exciting to learn how to design molecular structures from scratch, to organize them into functioning systems and to use them to explore new science. This is a very new research area – but we believe that we are on the verge of a technological revolution in manufacturing, information processing, biological research, and medicine.