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13 June 2000

How the Nervous System Takes Shape

Prof. Klaus Unsicker is the official spokesman of a new German Research Council-funded Long-Term Collaborative Research Project (in the following the German abbreviation SFB—for Sonderforschungsbereich—is used for convenience) at the University of Heidelberg. In an interview with Michael Schwarz he talks about the objectives of the Heidelberg research team.

Professor Unsicker, in January 2000—a symbolic date if ever there was one—the new Long-Term Collaborative Project on the molecular principles of neural development processes started its work. This so-called "SFB 488" is investigating issues with a major bearing on the future. How thought, language and feelings develop is a question that intrigues all of us. My question to you as Project spokesman: What is the new Project all about? What are its objectives?

Unsicker: The aim of SFB 488 is to contribute to a better understanding of neural functions. To put it simply, we want to find out how we are able to think, act, feel, be happy or sad. That's easily said. But understanding all the molecular details that enable even a small network of nerve cells to function is a gigantic and hitherto unsolved task. In Germany alone, there are scientists working on this problem in some 20 Collaborative Projects funded by the German Research Council and in many other programmes as well. SFB 488 is the first neurobiological project of this kind dedicated entirely to the development of the nervous system. We are out to understand the molecular principles behind the various stages in which the brain maps out and realises first apparently rough and then more and more detailed blueprints, how the various types of cell are determined, how cells migrate and link up their extensions, and finally how they start to communicate. And why do so many of them die before an organism is even born?

For a number of years now, the University of Heidelberg has been concerned to "enhance its profile", meaning above all to give its strong points a higher definition and improve them even further. The SFB 488 is obviously a reinforcement of the neurosciences and their standing in Heidelberg, coming as it does so soon after the establishment of the new Interdisciplinary Neuroscience Centre. Why developmental neurobiology in Heidelberg, why an SFB devoted to it?

Unsicker: Heidelberg has both a long-standing tradition, and above all a very lively ongoing commitment as a location of neuroscientific research at the molecular and cellular levels. Back in the final stages of SFB 317 ("Molecular Neurobiology") from 1994 onwards, it was apparent that Heidelberg was becoming something of a magnet for research scientists with a specific interest in developmental neurobiology. Hence the requirement put forward by the Research Council referees for a corresponding project area within SFB 317. And this was the germinal cell of SFB 488. The subject we're talking about here can only be adequately investigated on the basis of a long-term funding scheme like a fully-fledged Collaborative Research Project.

How will the new Collaborative Project benefit the University?

Unsicker: There's a simple answer to that: money, new structures, crystallisation points, expansion potential, a sharper profile and hopefully lots of scientists benefiting from funding, cooperation and constructive rivalry to achieve even grater excellence in their field than they would without all these things. From the perspective of the University and the state of Baden-Württemberg, one of the financially attractive things about SFBs is that they are 75% funded by the federal government, whereas other Research Council-funded instruments require 50% funding participation by the regional government. In the next three years SFB 488 will be receiving about 2.7 million marks from the Research Council. And the commitment required from the University in terms of basic outlay for the maintenance of the Project is relatively modest.

How will students profit from the new SFB?

Unsicker: A great deal. Not only because there'll be more doctorate opportunities available but also in terms of a diversification of seminars and other classes.

Is there any spin-off for medicine from research in developmental neurobiology?

Unsicker: Yes, at least in theory. Many molecular and cellular cascades involved in generative and degenerative processes in the brain—say in Parkinson's disease, Alzheimer, or multiple sclerosis—can be regarded in many ways as repetitions of developmental neurobiological events. Take the re-formation of myelin sheaths in multiple sclerosis. For this to happen, precursor cells of so-called oligodendrocytes have to divide, migrate and re-form the whole battery of specific proteins and lipids in the myelin sheaths and integrate them into meaningful and very complicated structures. So we believe that clinical medicine can profit from this kind of research. Neurobiological SFBs in Tübingen, Würzburg, Berlin and elsewhere have demonstrated convincingly how basic neurobiological research can be coupled with clinical fields like neurology, ophthalmology and otology. For Heidelberg and SFB 488 the referees have indicated in no uncertain terms that they expect more emphasis on the liaison with high-power clinical research.

The new SFB assembles research teams from the Universities of Heidelberg and Jerusalem, the German Cancer Research Centre, the Max Planck Institute of Medical Research and the European Molecular Biology Lab. Several of these teams were members of the very successful SFB 317 we've been talking about. You yourself would like to carry on that successful tradition and are confident that this can be done. Would you be prepared to go out on a limb and give us your vision of where research will stand in another 15 years' time?

Unsicker: Yes, I'll go out on a limb. First we hope that SFB 488 will have as long a life as possible and we're working on ways of ensuring that. The neurosciences will be one of the, if not the, leading discipline in the life sciences in the next decade. In ten years we will probably have deciphered the human genome in its entirety, likewise that of the most important model organisms, from the fruit-fly to the mouse. I don't think we can expect a complete understanding of the way all the 100,000 genes expressed in the human brain cooperate to engineer complex structures and functions. Many of the genes involved in the regulation of normal and abnormal behaviour will have been identified, and we may even be able to influence them externally. Technologies already in existence—quick comparison of the simultaneous regulation of thousands of genes, incredibly fast protein analyses, network observations and bioinformatics—will have taken us a long way towards understanding the higher functions of the brain.

What do the individual research areas look like? What methods will the SFB be using?

Unsicker: As far as methods are concerned, the sky's practically the limit. And this is something you would expect of any modern life science SFB. SFB 488 can draw on a broad spectrum of genetic, biochemical, cellular, physiological and morphological methods and has almost all the relevant models at its disposal, from the C. elegans nematode to genetic mouse mutants. The SFB is organised into four sections. The first looks at the molecular principles of neural induction, pattern formation and cell determination. The second investigates the growth and pathfinding principles of neuronal cell extensions. The third centres around the differentiation of nerve cells. And finally project section D studies the molecular principles behind the formation of synapses and neuronal networks.

What links are there between the SFB and other neurobiological research initiatives in the Heidelberg area?

Unsicker: You have already mentioned Heidelberg University's new Interdisciplinary Neuroscience Centre, the Cancer Research Centre, the Max Planck Institute and EMBL. In addition there are the University Postgraduate Research Groups working on neurobiology and developmental biology, the Research Council project "Aminergic Systems", the Neurological Hospital and, last but not least, the various biotechnology companies in and around Heidelberg.

How do the Research Council referees see the SFB? What are its strengths and does it have any weak points?

Unsicker: The strengths of SFB 488 are quite definitely the traditions it can build on in molecular and cellular research, the expertise of the University research teams and the crucial contributions from the Cancer Research Centre, the Max Planck Institute and EMBL. The involvement of non-University institutions are, in a sense, both a major asset of the SFB and a potential vulnerability. In this it is similar to many other SFBs. Research scientists at Heidelberg University have a reputation for excellence and that of course makes them much-coveted. In the period between our first approach to the German Research Council for this SFB and the final application—a period of about a year—about a third of the project leaders were offered attractive professorial posts elsewhere. These gaps now have to be filled, and frankly this ought to be done with the same uncompromising single-mindedness that American institutions display in such case. Unfortunately this has not been the case. But let's not be too defensive on this. The Research Council's appraisal was very positive and on occasion our Research Project has already been lauded as a "front runner" by independent observers. Personally, I'd prefer not to overstate the case, at least for the next few years.

(The interview is planned for publication in the 2/2000 issue of the University of Heidelberg's research magazine "Ruperto Carola", available from 17 July from: Pressestelle der Universität Heidelberg, Postfach 105760, D-69047 Heidelberg).

Please address any inquiries to:
Dr. Michael Schwarz
Press Officer of the University of Heidelberg
phone: 06221/542310, fax: 54317

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Updated: 08.07.2000


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