Projects

Late-onset neurodegenerative disorders such as Alzheimer´s disease, Parkinson´s disease and the polyglutamine disorders represent a major health care problem in view of the fact that millions of people worldwide suffer from these disorders and thousands are at risk. Besides, no effective treatment is available for these disorders to date.

The group focuses on deciphering molecular pathways contributing to the pathogenesis of late-onset neurodegenerative disorders such as Alzheimer´s disease and the polyglutamine disorders Huntington´s disease and spinocerebellar ataxia type 2. Despite insights into the cellular function of the disease-causing proteins, the pathogenic pathways underlying these disorders are far from being entirely understood, since these are complex systems involving many genes and protein-protein interactions. Hence, to comprehend the complexity of pathways implicated in these neurodegenerative disorders, it is essential to identify the cellular function of the respective disease-causing proteins, which is yet unknown for most of them, and to understand their role and involvement in the whole cellular network. For this, we combine respective yeast disease models, yeast genetics, yeast screens, functional and bioinformatic approaches in close collaboration with computer scientists. By means of yeast-2-hybrid screens and comparative proteome analysis we have identified several novel interaction partners of the SCA2 gene product, ataxin-2, and substantiated a function in the cellular RNA metabolism. By exploiting yeast genetics we discovered cellular processes potentially contributing to the pathogenesis of SCA2 and Huntington’s disease. To further comprehend the significance of the observed protein interactions in the cellular context and to validate their role in pathogenesis, we are developing in a combined effort with Dr. Zoltán Konthur a novel screening procedure resulting in a number of highly specific binding molecules that can specifically block protein-protein interactions of the target proteins. Thus, our combination of functional studies and technologies not only promise to be valuable tools in functional proteomics and genomics perspectives. The knowledge of occurring interactions - which can potentially be targeted - will finally help to develop therapeutic strategies in the future. Research lately performed in the group is also directed at modeling of pathways in response to specific stress conditions and at understanding regulatory and signaling networks in yeast in collaboration with computer scientists.

last updated: 27 November, 2007