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Helge Grosshans: Regulating the Regulators

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Recommended by: Frank Slack, Yale University

Helge Grosshans of the Friedrich Miescher Institute for Biomedical Research started out studying tRNA biogenesis as a PhD student, and around that time there were a couple of reports of a new type of RNA — microRNAs — coming out. "My guess was that there should be more of them," Grosshans says. He has since been proven right. There are thousands of known miRNAs that lend an extra layer of regulation to the genome, "a layer of gene regulation that no one had known anything about before and that is clearly important just to make an organism live and develop, and control cellular function," he adds. "It's very different from what people had focused on before, which was basically transcription."

While a number of people have influenced Grosshans' research, he says that he benefits from the environment at FMI, which has a number of people working with RNA that Grosshans can turn to. Indeed, being surrounded by good people in his own lab is the key factor to being successful, he says. "It's not just about me having great ideas and doing things, but I need to have people that are just as critical, creative and good at turning things into reality," he says.

Publication of note

One project in his lab looks at how miRNAs are themselves regulated — who regulates the regulators? When Grosshans started this work, the view in the field was that miRNAs, bound to argonaute, are stable and they may eventually degrade when argonaute does.

Using a genetic approach, Grosshans and his colleague Saibal Chatterjee identified a pathway for miRNA turnover, which they published in Nature in 2009. For this they used a C. elegans mutant with an miRNA that work sub-optimally, and then used RNAi to knock down ribonuclease to see if by hitting the right RNase, they would restore full miRNA function. "Then, we took it from there, doing biochemistry, doing genetics, doing cell biology, whatever it takes just to work it out," he adds.

"I think that what's cool about it is not just the conceptual finding, but also the fact that we were really doing serious biochemistry in C. elegans which historically is more of an organism where people do cell biology and genetics," Grosshans adds.

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