Stefanie Dimmeler: On the hunt for RNA snippets

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Stefanie Dimmeler is a Professor of Molecular Cardiology at the University of Frankfurt and is engaged in a hunt for RNA fragments that play a role in cardiovascular disease. Source: Dimmeler

15.10.2009  - 

Has she ever thought of pursuing a different career? “No,” replies Stefanie Dimmeler without a moment’s hesitation. “Research is absolutely my idea of fun.” The 32-year-old - a Professor of Molecular Cardiology at the University of Frankfurt, and Director of the Institute for Cardiovascular Regeneration – conducts her research not only with passion, but also with great success.Four years ago she was awarded with the prestigious Leibniz Prize from the German Research Foundation, and in 2008 she received a coveted grant from the European Research Council (ERC). The first results from the 2.4 million-euro project on the molecular biology of cardiovascular diseases have already been published.

MicroRNA is a word that crops up pretty frequently in the everyday life of Stefanie Dimmeler. This term, as the name suggests, refers to short RNA pieces that have a special function in the cell. Normal RNA serves as a form of instruction – it is transcribed and translated into the tools and components of the cell, i.e. into proteins. The microRNAs, however, which are approximately twenty nucleotides in length, are not transcribed. Their job is to regulate the gene activity of cells. “We know that during illness, cardiovascular disease for example, some of these microRNAs are disregulated,” explains the researcher. These candidates, which occur suddenly in higher or lower concentrations during cardiovascular disease, are Dimmeler’s main line of inquiry. The search, otherwise referred to as screening, was the first step in a five-year project.

Myocardial infarction and aging in the spotlight

The researchers in Frankfurt hunted not only for modified microRNA concentrations that occurred during infarction of the heart, but also those that occurred during aging. This is because the risk of infarction of the heart increases dramatically as we age. Dimmeler is hoping to scrutinise this connection on a molecular level. The group has already found five to ten high quality candidates during the screening in Frankfurt. “Interestingly, there are a few whose concentration changes in both conditions,” she says. But the real work is only just beginning. “We want to find out, of course, what this microRNA is doing; which target genes are actually influenced.” Indeed, they have already had success with one of their subjects - the results were recently published in the journal Science (2009, Vol. 324, S. 1710-1713) This has the somewhat unwieldy name of miR-92a, and is found above all in the cells of blood vessel walls, where it inhibits regeneration. The researchers were able to show that when this factor was suppressed following a heart attack, blood vessels formed more quickly, and damaged heart tissue recovered quicker than usual.

Dimmeler is satisfied with the progress of the project to date. Whether it will continue at such a quick pace is questionable. “The aging aspect will be more difficult, because we've got long, long lead times,” she says. The mouse that is used to investigate the aging process must be at least 18 months old. “No postdoc likes that,” says Dimmeler with a grin. One day, these microRNAs will serve as target for therapies - for example, by artificially modifying their concentrations. This has already proven to work quite well - at least in the laboratory. This is because miRNAs can be targetedly and effectively suppressed with specific molecules known as antagomers. Of course, there is a snag: “MicroRNAs do not only affect individual genes, but can change entire gene patterns,” explains Dimmeler. This sums up the problem faced by the research field. “These manifold target genes that have the miRNAs naturally make it difficult to study and understand the outcome.”

Full of enthusiasm

The researcher is not so sure whether this approach can generally be applied as a therapy for chronic diseases. For acute events, however, such as infarction of the heart, she is more optimistic. “I can already imagine it for short-term therapies,” she says. Although Dimmeler now is a professor, and since 2008 Director of the Institute for Cardiovascular Regeneration, she retains her enthusiasm for the research. “It's just exciting, this logical thinking, testing hypotheses, and then to have an explanation to pursue,” she says. To begin researching on a hunch, on the other hand, is not her style. “There are some areas in science where it’s best to think ahead about what you will do,” says Dimmeler, since 2008 a member of the German National Ethics Council. When you have weighed up the possible consequences, you can always decide for or against. “But just doing something, that you later have no interest in – that’s not my thing,” she says.

Author: Tom Finnis