"There are nearly 1,000 different miRNAs in humans, which control thousands of other genes, so this is really a major layer of gene regulation."
Micrograph of a C. elegans expressing green fluorescent protein in seam cells, a subset of skin cells that divide in a stem cell-like manner. The let-7 miRNA controls seam cell proliferation and differentiation.
"It continues to amaze me, and I find it very gratifying to see, how directly relevant many of the findings in the worm are to human disease."
March 8 2010
Helge Grosshans receives ERC grant for his microRNA research
Helge Grosshans, group leader at the Friedrich Miescher Institute for Biomedical Research, has received the European Research Council (ERC) Starting Independent Researcher Grant. This very competitive grant is awarded to highly promising scientists at the start of their independent career. Helge Grosshans received the ERC grant for his research on the biogenesis and turnover of microRNAs.
Q: Helge, recently you have received the ERC starting grant for your microRNA project entitled "Mechanisms of microRNA biogenesis and turnover". What makes microRNA so interesting?
Helge Grosshans: MicroRNAs (miRNAs) are small, genetically encoded molecules that regulate the expression of other genes. The first miRNA was discovered in the early 1990s, but what was the real surprise was the recent discovery that miRNAs are everywhere, involved in regulating virtually every cellular process in development and disease. For instance, there are nearly 1,000 different miRNAs in humans, which control thousands of other genes, so this is really a major layer of gene regulation. And still we do not understand fully how miRNAs are made or how they function. To complicate matters further (or, from our point of view, to make them more interesting), we have recently learned that miRNAs themselves are highly regulated, making for an even more intricate control network. There are a lot of fundamental questions yet to be answered, and we think we have an excellent system to tackle at least some of them. For instance, it was long thought that miRNAs are highly stable molecules, but we could identify a miRNA degradation pathway that prevents detrimental increases in miRNA levels and, possibly, regulates miRNA activity in development.
Q: You are working in the nematode C. elegans. How can this tiny worm help you answer your questions and will you be able to translate your findings into a biomedical application?
HG: The little worm has an amazing track record in this field. MicroRNAs were initially discovered in C. elegans, and for a long time it was thought that these small RNAs are in fact just a worm oddity. It took nearly a decade for the other systems to catch up, and to this day, many important insights on miRNA pathways continue to come from C. elegans. The traditional strength of C. elegans as a powerful genetic system is a major factor. In our lab, we have made some serious inroads into establishing biochemical assays for C. elegans, traditionally a neglected approach in this organism. This combination of genetics and biochemistry in one system is fantastic because it enables us to investigate the physiological significance as well as the mechanistic details of the pathways that we study.
Our research is fundamental biomedical research, but it continues to amaze me, and I find it very gratifying to see, how directly relevant many of the findings in the worm are to human disease. For instance, one of the earliest miRNAs discovered in C. elegans is let-7, a miRNA that regulates cell proliferation and differentiation. The exact same miRNA exists in humans, where it has the same function. We could even show that it regulates some of the same target genes in worms and humans, including the notorious proto-oncogene RAS. It is now clear that human let-7 is a tumor suppressor gene that is frequently down-regulated in cancers and there are intense efforts to harness this knowledge for therapeutic benefit. For instance, can we replace the missing let-7 by supplying synthetic let-7 from outside and thus block cancer progression? Or, particularly relevant to our studies on the biogenesis and regulation of miRNAs, what are the mechanisms that cause a decrease of let-7 levels in disease and can we reverse them?
Q: Many young scientists strive to receive an ERC grant. What does it mean to you to be granted this competitive award?
HG: This grant is really important - it gives us the financial muscle and flexibility to focus on ambitious and risky research ideas. It is not only the amount of funding that is important but also the duration - with five years' worth of funding, we don't need to go for the quick successes, we can take a more long-term view and take real risks. But beyond this, it is of course also a wonderful recognition of our past work and an encouragement for the future.