Understanding what our brain and muscles tell us


Silvia Arber © Valérie Chételat

Silvia Arber is a neurobiologist working on a map of the nerve connections between the head and the body. Her work increases our understanding of human dexterity. By Florian Fisch

For Silvia Arber, the photo sessions have become tedious. Since it was announced that the neurobiologist is to be awarded the Otto Naegeli Prize, she’s had to cope with a never-ending stream of journalists. Now they all want to take their own photos, despite her already having spent two hours at a professional photo shoot. Prof. Arber would much rather spend the time working in her lab. She even has a microscope set up in her little office, sandwiched between two laboratories, at the Biozentrum of the University of Basel. Nor is her microscope just for show or to impress her visitors – she uses it almost every day. She mostly examines slices of the brain or the spinal cord. It’s there that nerve cells from the brain meet motor nerve cells that transmit signals for muscles to contract. Arber is researching into how the nervous system steers our muscles. "Almost everything that the brain does has motor consequences", she says.

This focus on practical matters is typical of a pragmatic neurobiologist like Arber. She doesn’t think much of simulations of consciousness or of the ‘Human brain project’. They simply lack the neurobiological basics. We don’t even understand how the nervous system functions in the roundworm with its mere 302 nerve cells, despite all the connections between the nerve cells having already been mapped. Controlling muscles is a complex task. To demonstrate this, Arber always likes to show a picture of Roger Federer: only the subtle interplay of innumerable nerve cells allows for the smooth movements that world-class tennis players need. Not even Arber knows the exact processes involved. But that is what appeals to her: "What drew me to neurobiology is that we still understand so little".

A helping hand from the rabies virus

Her research team is studying the mouse. They observe, for example, how it takes hold of a tasty food tablet that is difficult to reach. "What interests us is how such motion sequences are controlled". She wants to know what types of nerve cells are linked to others. Thanks to her training as a cell biologist and molecular geneticist, Arber can distinguish between the different cells, based on their genetic activity. While working as a postdoc in New York, she studied how nerve cell extensions grow in an embryo and create connections to their neighbours. It results in accumulations of nerve cells with different functions at different points of the spinal cord and the brain. "We are constantly discovering new cell types", she says.

In order to make the connections between the nerve cells visible, Arber’s experiments make use of the rabies virus – a specialist in wandering through nerve cells. Researchers have altered the virus so that it can only leap over a single contact point and then gets stuck in the next cell. A fluorescent protein then makes this cell glow under a special microscope. When Arber and her team inject this virus into a muscle, they can find the controlling cells that activate the motor nerve cells in the spinal cord and the brain.

With this trick, Arber’s group has been able to make nerve cells visible in the brain stem. In the mouse, this part of the nervous system has more cell types to control the forelegs than the back legs, which explains their varying degrees of dexterity. And, in fact, the mice with a reduced number of muscle-controlling nerve cells were less able to grasp the food tablets than the group of unaltered mice. When Arber’s team also infected these controlling cells with the altered rabies virus, this led them straight to different motor centres in the brain of the mouse.

Accompanying Dad to the lab

Arber’s career planning was also done skilfully. She was appointed assistant professor at the Biozentrum of the University of Basel at the age of 31, without any detours along the way. "I was lucky to be able to research in excellent laboratories when I was a student", she says. In order to outdo the competition from Zurich, Basel at the same time offered her the chance to lead a group at the Friedrich Miescher Institute that is financed by Novartis. So she and her group now commute by bicycle over the Rhine and back. This dual post was important to her because there were hardly any neurobiologists at the Biozentrum back then, and she wanted to work with her established colleagues at the Institute. Today, she is the connecting link between two high level centres. "Neurobiology in Basel is at a high level and has grown immensely in the last ten years". Her father, the microbiologist and Nobel Laureate Werner Arber, was also based in the Biozentrum in Basel. As the elder of two daughters she often accompanied him to his laboratory on weekends and marvelled at the bacterial cultures she saw. During her studies she even attended lectures by her father. Whether she was influenced by his career, and if so to what degree, is difficult to say. "I don’t know what I’d have otherwise become", she says cautiously.

With her rabies virus method, Silvia Arber would like to penetrate even deeper into the brain. The centre of Parkinson’s disease could soon be reached. The potential medical relevance of her research was one of the reasons for her being awarded the Otto Naegeli Prize. But Arber sees herself as working primarily in basic research. She wants to find new things that no one before her has seen.

(From "Horizons" no. 102, September 2014)


Communication division
E-mail com@snf.ch