Biocurious is a weblog about biology, quantified.

It's (Almost) Alive!

by Andre on 25 March 2007

During a talk by Todd Squires at this year’s APS March meeting in Denver, he reminded me of a paper by Merkt et al. that showed they could make persistent holes in a liquid-like suspension of cornstarch when it was oscillated. But it’s not just that, at higher frequencies, they were able to open a portal to the netherworld through which the souls of the damned tried to escape. Seriously, just wait for the 2 minute mark.

I think if they had let it go for 10 more seconds it would have escaped the dish and then it would have been over for them.

That’s a pretty simple system that gives rise to very complex behaviour, but despite its appearance, it’s not that living. Is it possible to make a simple, totally synthetic system that would fit most people’s criteria of alive (e.g. growing, reproducing, evolving matter)? I think eventually we almost certainly will, but it may be sooner than you think.

Yi Jiang from Los Alamos Labs’ protocell project described some of their group’s recent work aimed at making synthetic living things. Steen Rasmussen, the project’s leader, wrote a paper [pdf] in Science with some other scientists working on protocells that outlines some interesting recent work. But since it’s basically a summary of a workshop so it doesn’t read so well. For an introduction (albeit to a different approach) I’d recommend the more readable description [pdf] from Szostak, Bartel, and Luisi. Both papers discuss the “bottom-up” strategies which involve coming up with a simple way to transmit information through a molecule or molecular assembly that can make copies of itself. The Szostak lab is focusing on RNA enzymes (ribozymes) because they can act as templates for making new copies of themselves but can also fold into functional structures that catalyze other reactions. Rybozymes that catalyze their own replication have already been discovered, but more work still needs to be done to improve their efficiency.

A micelle based protocellHaving an efficient self-replicating molecule is an important step, but it’s not everything. A more subtle but still important point is that groups of ribozymes need to be sequestered from each other to allow for evolution. The reason is that if a molecule mutates in such a way that it replicates RNAs faster, it gains no advantage in the population because it replicates all of the available template strands faster, not just copies of itself. Thus, to evolve, it needs to be in an environment where it is more likely to run into and replicate its daughter strands.

The most obvious solution to this sequestration problem is lipid vesicles. After all, lipid bilayers are ubiquitous self-assembling barriers in nature. But without all the accoutrements of modern cells, how do you make vesicles grow and divide? Szostak et al. suggest a few possibilities based on the biophysics of lipids, but the one stands out to me for its simplicity is also the one favoured by Rasmussen and his colleagues at Los Alamos. It turns the vesicle approach inside-out focusing instead on micelles. For a given lipid, micelle size is pretty fixed, so if you add lipids to the micelle it will soon break apart—a simple form of division. A great simple idea.

Despite these early successes, there are still significant challenges to overcome before anyone’s made a totally synthetic life form. Rasmussen’s team needs to move from theory and simulations to experimental realization while the Szostak lab needs to figure out ways to marry replicating ribozymes with dividing vesicles. Still, lots of people are thinking about these problems and I’ll speculate that some kind of minimal synthetic protocell will be realized within ten years. Unless of course an industrial cornstarch producer gets flooded and caught in an earthquake and the resulting ooze takes over the world…



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