Autocatalytic Sets Stars at Princeton

There were two standouts at the recent Princeton Origins of Life conference, Princeton University chemist Nilesh Vaidya and "world wide wandering" computer scientist Wim Hordijk, who both presented talks on autocatalytic sets.
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There were two standouts at the recent Princeton Origins of Life conference, Princeton University chemist Nilesh Vaidya and "world wide wandering" computer scientist Wim Hordijk. Vaidya and Hordijk each presented talks on autocatalytic sets. A lively round of questions followed, since as Vaidya pointed out in our interview (below), other scientists are investigating "template-directed polymerization processes" needing activated nucleotides, whereas his research involves an RNA recombination system in which the "number of bonds you're breaking is the number of bonds you're making."

Vaidya's experiment appeared October 2012 in Nature while he was still a graduate student at Portland State University. He is originally from Nepal. Prior to his paper's publication, Vaidya was offered a research position at Princeton, where he is currently a postdoc in the Brangwynne lab. He drove cross country through Hurricane Sandy just so he could arrive day one (November 1) at his new Princeton job.

Hordijk, who is Dutch, has roots going back to the golden days of the Santa Fe Institute, as a postdoc researcher and graduate fellow. Hordijk told me his model, which he calls RAFs, grew out of Stu Kauffman's 1971 concept of Collectively Autocatalytic Sets (CAS).

He and New Zealand mathematician Mike Steel of the University of Canterbury were fascinated by Vaidya's RNA recombination experiment and decided to do a computer simulation.

Hordijk is one of the presenters at COOL EDGE 2013, the Origin of Life conference at CERN, which kicks off February 26 with autocatalytic sets a principal theme.

Excerpts of my Princeton interview with Wim Hordijk and Nilesh Vaidya follow.

Suzan Mazur: Nilesh, what you and Wim are talking about hasn't really been represented in any other part of the Princeton Origins of Life conference.

Nilesh Vaidya: Not really. The system I describe relies on recombination events to produce autocatalytic sets.

Suzan Mazur: People can't get their hands on it?

Wim Hordijk: Yes. It's at a more abstract level.

Suzan Mazur: But the concept is over 40 years old. Stuart Kauffman talked about it in 1971.

Nilesh, to get your experiment working, what do you put in? You said you put in RNA.

Nilesh Vaidya: Fragments of RNA in buffer. These fragments come together and are stitched together to RNA enzyme. Once one RNA enzyme is formed, it can make more enzymes. In this study, we designed different versions of this enzyme and demonstrated that autocatalytic sets can emerge spontaneously.

Wim Hordijk: Did you replicate the experiment?

Nilesh Vaidya: Yes.

Wim Hordijk: How many times roughly?

Nilesh Vaidya: As far as I can remember, at least three times.

Wim Hordijk: So in principle you could go back and check whether it's really a different sequence of autocatalytic sets in each replication.

Nilesh Vaidya: Yes.

Wim Hordijk: Interestng. That's what I get in simulation. Every time I run it I get a different sequence.

Suzan Mazur: Why does this seem to make more sense to you than some of the other origin of life approaches?

Wim Hordijk: Most of the people here are trying to find a very specific pathway for how RNA could have come into existence given what we think was available on the early Earth. My work is looking at processes. I'm a computer scientist. When I think about a problem I think in terms of algorithms and processes.

Suzan Mazur: And at some point you're going to actually do the experiment. Or work with someone who will do the experiment.

Wim Hordijk: That's the idea.

Nilesh Vaidya: I do experimental work. Going back to your question about how is this different from the other systems we've studied -- our system is dependent on recombination events compared to the other systems which study template-directed polymerization processes ... In those [template-directed] systems you need some activated nucleotides, you need some high energy molecules for a polymerized system to take over. But in a recombination system ... the number of bonds you're breaking is the number of bonds you're making at the same time. So you don't need activated molecules.

Suzan Mazur: Do you deal with spacial effects like McMaster University's Paul Higgs discussed in yesterday's presentation? Does that come into your work?

Nilesh Vaidya: That's actually something we want to try next with the system we have. We talked about how these systems can evolve. We want to see if we can get some different network structure to what we have if there's no compartment.

Suzan Mazur: Do you think this is the way forward? Is this the cutting edge stuff?

Wim Hordijk: It's something I'm excited about. But it's science, we don't know.

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