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Viral Metagenomics Sample Globally: SDSU’s Rohwer on Phage Discovery

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Forest Rohwer goes to great lengths to study phages wherever they’re found. Whether he’s taking samples from each of the world’s oceans for a global marine phage study or sifting viruses from lung and gut bacteria, his goal is to better understand the biology of phages — the most abundant biological entities on the planet.

Rohwer’s road to environmental metagenomics is not exactly long, but it did wind a little at the start. After finishing up a PhD in immunology, he planned to become a lawyer. But this fell by the wayside when he caught a talk by Farooq Azam, the Scripps Institution of Oceanography researcher whose microbial ecology work interested Rohwer enough to join the lab as a postdoc. Now an assistant professor at San Diego State University, Rohwer has been working on marine and human viruses ever since.

In Rohwer’s 20-some person lab, several lines of study cross-pollinate in the search for “universal rules for how ecosystems are set up.” To this end, one group studies distinct viral communities in various places, an activity that’s supported by a computational biology core that models the dynamics of those communities. Others work on coral reef biology, looking at how microbes are overgrowing and killing reefs. Rohwer’s group also applies metagenomic approaches to looking at human viruses that live in human blood, gut, and lungs.

Viruses that dwell in the human gut were the subject of a recent study to which Rohwer lent his expertise. The study, published in PLoS Biology and led by Yijun Ruan of the Genome Institute of Singapore, presented a comparative metagenomic analysis of RNA viruses found in healthy human fecal samples. “Very little data is out there about RNA viruses,” Rohwer says. “It’s a pretty open field, though that’s true in general with virology.”

That may have something to do with how tricky it is to collect and measure viruses. “Not only do you have small amounts of DNA, you also have single-stranded DNAs, single- and double-stranded RNAs, and phages [that] have modified DNA, which can’t be cloned directly into something like E. coli,” Rohwer says. Complications with cloning viral DNA prompted him to adopt 454’s pyrosequencing technology for viral sample analysis. “The 454 is beautiful from our point of view because we can get such a great feel for how the sample looks, for what’s there and how it’s structured,” he says.

Pyrosequencing metagenomes generates huge amounts of data. To make sense of it all, Rob Edwards, a bioinformaticist in Rohwer’s lab and a member of the Fellowship for the Interpretation of Genomes, has been working to integrate viral genome annotation data with the Phage Proteomic Tree, the first sequence-based taxonomic systems for phage. “The advantage of having some sort of taxonomy system in place is that you can then ask questions along the lines of, ‘Is the phylogenetic makeup of this area different from the next one?’” Rohwer says. He adds, “The hope is always to lead back to some kind of biology.”

 

— Jen Crebs

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