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Metabolomics IMSB’S Sauer uncovers roles for Doppelganger genes

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In the six months since Uwe Sauer joined ETH Zürich’s Institute of Molecular Systems Biology, he’s managed to put together a lab, publish more than a dozen research publications, and complete the largest functional classification of duplicate genes to date.

Apparently it’s not the Swiss air that fosters such prolificacy, but rather the fact that Sauer’s five-year quest to “develop technology for the global assessment of molecular traffic” has culminated in a complex of tools and methods ideal for tackling questions in metabolomics. Molecular flux analysis — tracking carbon molecule traffic within cells via the use of carbon-13 labeling and sensitive mass spec, then fitting that data to a mathematical model — is a key approach in Sauer’s repertoire.

In a recent paper for Genome Research, Sauer’s team looked at the phenomenon of functional gene duplicates involved in yeast metabolism. Contrary to previous reports that focused on a single mechanism responsible for the retention of duplicates, Sauer’s group found that “at least for yeast metabolism, the persistence of the duplicated fraction of the genome can be better explained with an array of different, often overlapping functional roles,” he says. That array of roles includes four distinct mechanisms that were uncovered by looking at quantitative measurements, such as flux, in terms of computational models, he says.

For future research lines, model microbes like yeast will almost certainly remain in a starring role, but moving into more complex systems is one of Sauer’s goals. That said, he affirms that “any higher cell is in a totally different situation.” Carbon molecule traffic changes constantly in higher systems, he says, so it is necessary to develop new methods before moving away from yeast.

“That’s what really drives us as a group,” Sauer says about the integration of information gleaned from various sources. Since joining Ruedi Aebersold at IMSB in July, Sauer has continued to “develop technology and try to apply it to industrial process development, but also to medically related problems.” Lucas Pelkmans, the institute’s RNAi expert, started a lab one month after Sauer, and the three PIs are actively working to foster “cutting-edge technology development.”

— Jen Crebs

 

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