At the BIOMS Centre for Modelling and Simulation in the Biosciences young scientists are using new methods to investigate complex biological processes Funding comes from the Klaus Tschira Foundation, the State of Baden-Württemberg, the University of Heidelberg and other research institutions
Much of what we take for granted today would be unthinkable without computer models and simulations: modern cars and aircraft, navigation systems or the animated meteograms we see every evening in the TV weather forecast. In the biosciences, by contrast, modelling and simulation are still in their infancy. The first German Centre for Modelling and Simulation in the Biosciences (BIOMS) was set up in early 2004 to close this gap. The Centre is part-funded (two thirds) to the tune of 2.5 million euros each by the Klaus Tschira Foundation and the State of Baden-Württemberg. The remaining third is supplied jointly by the University of Heidelberg, the German Cancer Research Centre (DKFZ), EML Research, the European Molecular Biology Laboratory (EMBL) and the Max Planck Institute for Medical Research. This funding will be provided for a period of five years. The resources are used exclusively to support the research work of young scientists. In its objectives and the support it gives to young researchers BIOMS is a unique project, unparalleled anywhere else in the world.
The BIOMS resources have been used to establish three new research groups at EMBL, DKFZ and the Interdisciplinary Centre for Scientific Computing (IWR) of the University of Heidelberg. Here modelling and computer simulation are used to investigate biological systems. These methods make it possible for complex biological processes to be studied not only "in vivo" (in the living organism) or "in vitro" (in the test-tube) but increasingly "in silico" (with the aid of computer programmes). First the scientists devise models based on lab experiments, then they test the accuracy of those models with computer simulations and derive new experiments and explanatory models from the results.
At present, more than a dozen young scientists are going about their research work under the supervision of Dr. Francois Nédélec at EMBL, Dr. Ulrich Schwarz at IWR and Dr. Matthias Weiss at DKFZ. Another seven young BIOMS researchers are working at the above-named locations and at other institutions involved in the project EML Research and the Max Planck Institute for Medical Research. Some two years after taking up their duties, the three group leaders have now become key figures in Heidelberg's activities in the field of quantitative biology. They are the joint organisers of the BIOQUANT-BIOMS Seminars regularly attracting large audiences to the lectures taking place there. They also played a crucial role in the successful proposal for the Cluster of Excellence "Cellular Networks" and the research unit "Systems Biology of Virus-Cell Interaction (VIROQUANT)" funded by the Federal Ministry of Education and Research.
How do precisely operating cellular structures evolve from uncoordinated proteins?
Cellular protein structures manage to perform biological functions with astonishing precision, though these structures ultimately derive from proteins moving in an apparently uncoordinated manner. Dr. Francois Nédélec and his BIOMS research group at the European Molecular Biology Laboratory are investigating this phenomenon. With reference to the mitotic spindle, a cellular structure evolving during cell division and ensuring that the chromosomes separate, Nédélec is trying to find out how proteins contrive to engage in this spontaneous form of self-organisation. His latest findings indicate that the spindle structure is in fact not static but highly dynamic. Protein fibres within the spindle shrink or disappear within a few minutes if necessary. New protein fibres evolve just as flexibly. Outwardly, however, there is hardly any sign of what is going on. The external appearance of the spindle can remain apparently unchanged for hours.
In fact, not one of the proteins forming the spindle remains within it for long. It is their permanent interaction that gives the outwardly unchanging overall structure its form. "The spindle retains its external form and size," says Francois Nédélec. "At the same time it develops the balancing forces required to ensure that chromosomes can be precisely positioned in the cell and separated from one another."
The research work done by the scientists is designed to enhance our understanding of severe illnesses and thus improve the prospects of curing them. One example is cancer, which results from the uncontrolled and excessive division of cells. The complexity the scientists are confronted with is immense. Accordingly, the use of simulations is especially valuable in enabling Francois Nédélec to verify his own "in vitro" experiments and the models evolving from them.
For more information go to http://www.cytosim.org/
The Adhesive Power of Cells
What holds tissue together and how do cells stick to surfaces?
One of the most important tasks cells perform is to adhere to their surroundings. In the body, cells attach themselves to soft surfaces. White blood corpuscles stick to vessel walls before hunting down foreign bodies in the adjoining tissue. Tissue cells are in constant contact with other cells or the binding material between them. Cancer cells leave the tissue to form metastases elsewhere, cells stick together to heal wounds. Recent experimental studies have indicated that in lab experiments they grow more quickly and even take on a different form on hard surfaces like glass and plastic than they do on soft surfaces more closely resembling the situation in the body. These findings are expected to play a major role in biomedical applications such as the grafting of implants. For a number of years, the theoretical physicist Dr. Ulrich Schwarz has been intrigued by the way cells manage to adhere to surfaces and react to forces like traction and pressure. With his BIOMS research group at Heidelberg University's Interdisciplinary Centre for Scientific Computing, Schwarz has been probing the frontiers between physics and biology. The scientists are working on a theoretical model assisting them in explaining the role of mechanical forces in cell adhesion. They are attempting to establish how individual proteins are connected and how forces influence the transmission of signals in the cell. They already have some initial results to show for their efforts. In conjunction with experimental scientists at the Weizmann Institute in Rehovot (Israel), the research group has found that forces exerted from the outside make contacts grow.
"We are also working on the simulation of the 'rolling adhesion' phenomenon," says Schwarz. This is a form of cellular motion that occurs, for example, before white blood corpuscles proceed from blood vessels to the surrounding tissue. The scientists have been able to explain why "rolling adhesion" only occurs upwards of a certain flow speed. In the body this is probably designed to prevent the white blood corpuscles from adhering to the wrong places.
For more information go to http://www.iwr.uni-heidelberg.de/organization/bioms/schwarz/
Containers to Destinations
How do cells transport valuable freight?
Membranes form the outer envelope of every living cell. In the cell interior membranes also separate off different areas performing different functions. The cell nucleus membrane encloses the genetic substance containing the information for building proteins. Other membranes are sites for synthesis, quality control and protein modification. A lively exchange of molecules takes places between these reactive sites. For this exchange the cell uses little containers called vesicles that develop out of the membranes. As required, transport vesicles bead off from the membranes and carry proteins to a different place. Little is known about these cellular transport pathways. With his BIOMS "biological membranes" research group at the German Cancer Research Centre, Dr. Matthias Weiss is investigating the cells' container system.
Severe diseases like diabetes, cystic fibrosis and cancer can interfere with the container system. Vesicle transport itself can also cause illnesses, for example when the transport of certain proteins to the outer cell membrane is not functioning properly or signals from outside are wrongly processed by the cell. The scientists use simulations to find out more about the transport pathways of the vesicles. Their special interest centres around so-called exit sites, the places where new vesicles originate in the cell's internal membrane system. "Learning more about transport processes in the cell interior is of major importance," says Weiss. "Our work is designed to help devise new therapy approaches for these illnesses."
Background information at http://www.dkfz.de/en/cellular_biophysics.html
The first German Centre for Modelling and Simulation in the Biosciences (BIOMS) opened in Heidelberg in early 2004. Here modelling and computer simulations are used in research on biological systems. The resources of the new Centre are employed exclusively for the advancement of young scientists. The institutions involved are the German Cancer Research Centre, EML Research (the research institute of the Klaus Tschira Foundation), the European Molecular Biology Laboratory, the Max Planck Institute for Medical Research and the University of Heidelberg (Interdisciplinary Centre for Scientific Computing and Centre for Molecular Biology). The coordinators are Prof. Dr. Willi Jäger (University of Heidelberg) and Dr. Ursula Kummer (EML Research). The Centre is part-funded (two thirds) to the tune of 2.5 million euros each by the Klaus Tschira Foundation and the State of Baden-Württemberg. The remaining third is supplied jointly by the institutions involved. For more information go to www.bioms.de
In 2007 the BIOMS research groups will be moving into the new Bioquant building on the University of Heidelberg campus (http://www.bioquant.uni-heidelberg.de).
Please address any inquiries to:
Klaus Tschira Foundation gGmbH
phone: +49 6221 533214
fax: +49 6221 533198
online : www.kts.villa-bosch.de
For the University of Heidelberg
Dr. Michael Schwarz
Press Officer of the University of Heidelberg
phone: 06221/542310, fax: 54317