Category: General

I’ve been in Leeds for a few days for the biennial conference of the Polymer Physics Group of the UK’s Institute of Physics. Among many interesting talks, the one that stood out for me was the first – an update from Andrew Turberfield on his efforts to make a molecular motor from DNA.

Turberfield, who is at the Oxford IRC in Bionanotechnology, is building on the original work from Ned Seeman, exploiting the remarkable self-assembling properties of DNA to make nanoscale structures and devices. A few years ago, Turberfield, working with Bernie Yurke at Lucent Bell Labs, designed and built a DNA nano-machine (see here for a PDF preprint of the original Nature paper), and in 2003 they published a paper describing a free-running motor powered by the energy released when two complementary strands of DNA meet to make a section of double helix (abstract here).

This motor doesn’t actually do anything, apart from sit around in solution cyclically changing shape. What Turberfield wants to do now is make something a bit like the linear motors common in cell biology, in which the motor molecule moves along a track, often carrying a cargo. To make this kind of molecular railway, Turberfield’s scheme is to prepare a track along a surface by grafting strands of DNA to it. The engine is another DNA molecule; what needs to be done is get some scheme whereby the engine molecule is systematically passed along from strand to strand.

His first effort, in collaboration with Duke University’s John Reif, involves using enzymes to alternately cut DNA strands and rejoin them in a sequence that has the effect of making a short strand of DNA move linearly in one direction. In this case, it’s the energy used by the enzyme that joins two bits of DNA that makes the motor run. The full paper is here (PDF). In motor mark 2, it’s a so-called nicking enzyme that makes the engine move, and the directionality is imposed by the fact that the track is destroyed in the path of the engine (abstract here, subscription probably required for full article). What Andrew really wants to do, though, is have a motor that is solely powered by the energy released when DNA strands make a helix, which doesn’t chew up the track behind it, and which doesn’t involve the use of any biological components like enzymes. He has a scheme, and he is confident that it’s not far off working.

These motors are inefficient and slow in their current form. But they are important, because they work on the same basic principles as biological motors, principles which are very different to the mechanical principles that underly the motors we are familiar with. They rely on the Brownian motion and stickiness of the nanoscale environment. But because of the simplicity of the base pair interaction, the calculations you need to do to predict whether the motor will work or not are feasibly simple. By learning to make model railways from these simple, modular components, we’ll learn the design rules that will enable us to make a wider variety of practical nanoscale motors.

I wrote below about Craig Venter’s vision of synthetic biology – taking an existing, very simple, organism, reducing its complexity even further by knocking out unneccessary genes, and then inserting new genetic material to accomplish the functions you want. One could think of this as a kind of top-down synthetic biology; one is still using the standard mechanisms and functions of natural biology, but one reprogrammes them as desired. Could there be a bottom-up synthetic biology, in which one designs entirely new structures and systems for metabolism and reproduction?

One approach to this goal has been pioneered by Steven Benner at the University of Florida. He’s been concentrating on creating synthetic genetic systems by analogy with DNA, but he’s not shy about where he wants his research to go: “The ultimate goal of a program in synthetic biology is to develop chemical systems capable of self-reproduction and Darwinian-like evolution.” He’s recently written a review of this kind of approach in Nature Genetics Reviews (subscription only): Synthetic biology.

David Deamer, from UC Santa Cruz, has a slightly different take on the same problem in another recent review, this time in Trends in Biotechnology (again, subscription only, I’m afraid). “A giant step towards artificial life?” concentrates on the idea of creating artificial cells by using self-assembling lipids to make liposomes (the very same creatures that L’Oreal uses in its expensive face creams). Encapsulated within these liposomes are some of the basic elements of metabolism, such as the mechanisms for protein synthesis. How close can this approach get to creating something like a living, reproducing organism? In Deamer’s words: “Everything in the system grows and reproduces except the catalytic macromolecules themselves, the polymerase enzymes or ribosomes. Every other part of the system can grow and reproduce, but the catalysts get left behind. This is the final challenge: to encapsulate a system of macromolecules that can make more of themselves, a molecular version of von Neumann’s replicating machine.” He sees a glimmer of hope in the work of David Bartel at MIT, who has made a RNA enzyme that synthesizes short RNA sequences, pointing the way to RNA-based self-replication.

But all these approaches still follow the pattern set by the life we know about on earth; they depend on the self-assembling properties of a familiar repertoire of lipids and macromolecules, like DNA, RNA and proteins, in watery environments. Could you do without water entirely? Benner is quoted in an article by Philip Ball in this week’s Nature (Water and life: Seeking the solution, subscription required) arguing that you can: “Water is a terrible solvent for life…. We are working to create alternative darwinian systems based on fundamentally different chemistries. We are using different solvent systems as a way to get a precursor for life on Earth.”