Who works together with whom? This is the question scientists at the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch have investigated with regard to human proteins. The answer can be found within a map - the first one in international research - showing 3,186 interactions between 1,705 human proteins. Among them: 531 previously unknown interactions involving 195 disease proteins, highly relevant for medical research. "We have laid the foundation for a comprehensive connection scheme of the human body. The map helps us understand the functions of proteins and the complex processes in our cells," explains Professor Erich Wanker, who directed the study. The work of Professor Wanker and Dr. Ulrich Stelzl, to which scientists from the Max Planck Institute for Molecular Genetics (Berlin) and the German Resource Center for Genome Research GmbH (Heidelberg) contributed, has now been published in the online edition of Cell* (DOI: 10.1016/S0092867405008664). The researchers were able to conduct the project, which is the first extensive human protein network to be published, with the support of the National Genome Research Network (NGFN) - a large scale biomedical program initiated by the German Federal Ministry for Education and Research (BMBF). The NGFN enables scientists to systematically investigate human genes and proteins and their role in health and disease.
With their new map, the MDC scientists hope to better understand the onset of diseases and to discover new molecular targets for therapy. They have identified new protein interactions that can modulate cellular signalling cascades like the Wnt pathway, important in the development of human cancers. "Our interaction map sheds new light on the function and dysfunction of many proteins", according to Professor Wanker.
The extensive studies on human protein-protein interactions were carried out with a special technology: the automated yeast two-hybrid system (Y2H). In this method, yeast cells are employed to identify the binding partners of proteins. "Interaction studies used to involve laborious manual procedures. Now, a robot system processes thousands of reactions as fast as lightning," Erich Wanker explains. "We established the robotics unit four years ago and are proud to be the first lab to present a large scale human protein network to the community," say Wanker and Stelzl, after testing 25 million protein samples and creating a database that gives full access to the results to fellow scientists.
*A Human Protein-Protein Interaction Network: A Resource for Annotating the Proteome
Ulrich Stelzl1, Uwe Worm1, Maciej Lalowski1, Christian Haenig1, Felix H. Brembeck1, Heike Goehler1, Martin Stroedicke1, Martina Zenkner1, Anke Schoenherr1, Susanne Koeppen2 , Jan Timm1, Sascha Mintzlaff1 , Claudia Abraham1, Nicole Bock2, Silvia Kietzmann2, Astrid Goedde3, Engin Toksöz1, Anja Droege1, Sylvia Krobitsch2, Bernhard Korn3, Walter Birchmeier1, Hans Lehrach2 and Erich E. Wanker 1,2*
Cell, Vol 122, Issue 6, 1 September 2005
1Max Delbrueck Center for Molecular Medicine, 13092 Berlin-Buch, Germany
2Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany
3German Genome Resource Center, 69120 Heidelberg, Germany
Message posted by: Frank S. Zollmann
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