Charité Campus Virchow-Klinikum
Augustenburger Platz 1
Professor at the Institute of Human Genetics, Humboldt-Universität zu Berlin
We investigate mouse models for neurodegenerative diseases such as Alzheimer, Parkinson and Huntington disease. In these mice a gene/protein well known to be crucial for the development of one of these diseases is knocked out or overexpressed. We investigate the brain proteins of these mice with methods of proteomics. This includes two-dimensional electrophoresis for separating the proteins, mass spectrometry for protein identification, other biochemical methods for protein characterization and sophisticated software for comparison of electrophoretic protein patterns and for protein quantification. In these investigations we made the surprising observation that when ever a gene is mutated (knock out, overexpression) up to several hundreds of proteins show quantitative alterations (up or down regulation). Our interest is now focused on this phenomenon. Our results suggest that disease specific metabolic pathways affected by a mutation are always accompanied by proteome wide perturbations in the cells. It has been realized in the past several years that the proteins in the cell interact in large protein-protein networks and this may explain our observations. As a consequence, we now investigate our disease mice in embryonic development to study the protein changes which precede a genetic disease. Here we also consider the influence genetic protein polymorphisms may have on the robustness of the proteome. Our investigations include studies of transfected embryonic and adult stem cells in course of differentiation. Our research is closely related to problems in regenerative medicine. For example, characterizing, on the proteome level, omnipotent embryonic stem cells in comparison to differentiated cells may show us, how cell lines applicable for therapeutic purposes have to be designed molecular genetically.