Jens Brüning: Builder of bridges in genetics

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Jens Brüning is a geneticist at the University of Cologne. Source: Brüning/Universität Köln

29.06.2009  - 

How does the brain know that the body has enough energy to carry out its assigned tasks? When should it curb the appetite? And what effect does the allowance of sugar have on ageing? These are just some of the questions that Jens Brüning has been asking during his six years as Professor at the University of Cologne's Institute of Genetics. Some answers have indeed been forthcoming. Two years ago, Brüning received the prestigious Leibniz Award for his work, followed this year by the 150,000-euro Ernst Jung Award.

Jens Brüning sees himself as a builder of bridges: "We want to actually transfer the things that we're working on in mice genetics to human clinical trials," says the scientist. Since 2003 the physician has had a professorship at the Institute of Genetics, where he is concentrated on basic research into metabolism. Nevertheless, Brüning has not yet turned his back on practical medicine: "I also work in parallel at the university clinic in the areas of endocrinology and metabolism." The findings that the scientists are hoping to implement involve diabetes, obesity and insulin. Certainly, the surrounding statistics suggest that all three are connected. Of the more than 6.5 million Germans diagnosed with type 2 diabetes, at least eighty to ninety percent are overweight.

Insulin is a hormone produced by Langerhans' islet cells in the pancreas, and is distributed when blood sugar levels become too high. "It was assumed that the effect of insulin is to increase the sugar intake in muscles and fatty tissue, and to ensure that the liver produces less sugar," says Brüning. In type 2 diabetes — age-related diabetes — insulin no longer has this effect. The cells' insulin receptors become unresponsive to messenger substances.

The search for insulin in the brain
However, this insulin regulation mechanism is only partially understood. "Over the last few years it has become clear that the insulin effect in the brain affects the regulation of sugar release." The idea of searching for hormones in the brain is fairly new, and is founded on a still not entirely solved conundrum: The insulin receptors in the brain. "They are there, but nobody really knows what they do," says the researcher. In order to solve this conundrum, the group bred mice that were missing these receptors. "We found that these mice become slightly overweight," says the researcher. The conclusion is clear: Insulin is one of the signals that notify the brain about how much energy is stored in the body. The highest of our organs needs this information to reduce the intake of food. "If this feedback information is missing, the mice eat more, even though they have enough fat," says Brüning.
The researchers in Cologne also succeeded in revealing exactly which nerve cells are responsible for this by breeding mice that were lacking the receptor, but only in individual regions of the brain. "From the billions of nerve cells in the brain, we have found a group of about 3000 cells in the hypothalamus," says Brüning. These appear to control liver metabolic activity. If the insulin receptor is lacking, sugar formation in the liver is no longer sufficiently inhibited, and blood sugar levels rise.

Insulin influences not only sugar metabolism

The sugar metabolism is unlikely to be the only thing influencing insulin in the brain. "In lower organisms such as nematodes or flies, it appears that insulin action in the central nervous system is in fact involved in the regulation of longevity," says Brüning. The findings in mice are currently somewhat controversial. Although these results come from other groups, Cologne also wants to pick up the topic. Not least because the new Max Planck Institute for Biology of Aging, headed by Linda Partridge — one of the leading figures in Aging Research — was only recently founded on the campus. "Up to this time she has been studying flies," says Brüning, "and we are now working together with our mouse models." This is one of the topics in the focus of the cluster of excellence "Cellular Stress Responses in Aging-Associated Diseases".

That Brüning is following up his work in Cologne, was not to be taken for granted. After studying medicine in Cologne, he spent nine years at the Joslin Diabetes Centre at the Harvard Medical School in Boston, USA. "This is one of the best laboratories for insulin action", says Brüning, justifying his decision. The researcher would have been happy to stay at Harvard, but the family of five ultimately chose Germany as its future home. "The three children are all real Colognians," says Brüning with a smile. And does he generally encourage a stay in the United States for his students? "There are many places in the world where you can conduct excellent science. This need not necessarily be the US," he says diplomatically. His advice: You should change your place of study at some point in order to learn about different approaches to scientific work. Or more concisely: "One should get to see a few different things."

Author: Miriam Ruhenstroth