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Elucidating Evolution, Virus by Virus

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  • Title: Assistant Professor, Department of Biomedical Informatics, Columbia University College of Physicians and Surgeons
  • Education: PhD, Universidad Autonoma de Madrid, Spain, 2001
  • Recommended by: Bud Mishra

It may be a far cry from elucidating the finer points of spacetime, black holes, and quantum mechanics, but Raul Rabadan is thoroughly content with his decision to leave the world of theoretical physics for a research post working on RNA viruses. Just two years ago, Rabadan was hard at work  publishing papers on string theory as a postdoc at the Institute for Advanced Study at Princeton, when he began to take notice of the school's new center for systems biology. "I started talking to a colleague of mine, another string theorist who was working in biology, and found that what they were doing was rather interesting," says Rabadan. "Then, I decided to collaborate with them, and then at some point, I just decided to switch fields."

Rabadan says he likes the fact that, from a basic scientific point of view, viruses are excellent models for understanding how living organisms work and evolve. "Even if we sequence every human on the Earth, the question becomes, how can we deduce the history and the pressures? How do we deduce selection for some particular genes and how these genes are evolving in disease, given the data?" says Rabadan. "But with viruses, you can see how they are evolving with time because they are evolving very fast. So I think viruses can give us a very good understanding of evolution — not to mention they are burdens to our society, and understanding how they work is something very important."

Rabadan's current area of focus is the analysis of RNA viral evolution, which happens at a much faster rate than many other model systems. He and his colleagues are currently working on ways to analyze thousands of viral RNA genome datasets — with particular targets of HIV and influenza — in order to better understand their evolution and epidemiology. "We have a lot of samples, such as the 1918 flu, which, almost a century later, has changed almost 15 percent of its genome," he says. "So if we take a mammalian example, that's like comparing a mouse to a human, so we have an idea of how evolution is working — population genetics, mutation, and selection."

In order to find the changes that take place over time in RNA viral genomes, which can run from 1,000 to 100,000 base pairs in length, he and his fellow investigators have developed algorithms capable of large-scale comparative analyses of human and avian viral genomes. Through such methods, they have demonstrated evidence supporting the hypothesis that the H1N1 strain of the influenza virus entered the human population before the actual 1918 outbreak, possibly as early as 1910.

Publications of note

In a 2006, Rabadan published a paper entitled "Comparison of human and avian influenza A viruses reveals a mutational bias on the viral genomes" in the Journal of Virology. In it, Rabadan and his colleagues presented what he calls a very "nice and simple idea" that aims to improve understanding of viral outbreaks. The aim of their research was to uncover and characterize the changes a virus undergoes as it jumps from one host to another — in this case, from bird to human — usually resulting in pandemics such as the 1918 influenza virus. After the analysis of several genomes of different viruses living in birds and humans, the researchers discovered that viruses evolving in different species' host organisms have very distinctive mutation patterns.

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