Time: Tuesday April 13th, 0915 - 1000
Place: UMB, Dept of Animal & Aquacultural Sciences, meeting room 2nd floor
An intricate intracellular network of interactions controls aging and is perturbed in age-related diseases, including Alzheimer’s and Parkinson’s Disease. We set out to identify the individual components of this network, their interactions with distinct cellular pathways, and the consequences of mutations resulting in disease. Here, we will discuss an interdisciplinary platform that war are currently automating to systematically combine the identification of protein interactions, substrate/kinase relationships and in vivo functional validations. As a proof of concept, we focus on identifying the human interactome of Parkinson’s Disease related proteins. For this purpose, we first screened for interactors of five proteins affected by mutations in familial forms of PD. We use cell culture and C. elegans systems to validate the evolutionarily conserved protein-protein and protein/kinase interactions. We then used high-throughput procedures for the biochemical and genetic validation of the interactions. In combination with computer-based annotations of the interactions, a prediction of the identified network suggested a common function of PD associated factors in the control of cytoskeletal dynamics that are the prerequisite for cell migrations, neuronal outgrowth and engulfment of apoptotic corpses. Using C. elegans as a genetic in vivo toolbox, we verified the predictions in an animal model. Our data support a genetic and functional connection of PD associated genes to genes involved in the control of cellular aging. The interaction platform is universally applicable and may help to elucidate functional network involved in cell biology and disease. Ralf Baumeister is a Professor of Bioinformatics & Molecular Genetics (Biology) and of Molecular Medicine & Cell Biology (Medicine) at the University of Freiburg and is acting director of the newly established Freiburg Center for Systems Biology (ZBSA). His research interests are the development and exploitation of disease models using the nematode Caenorhabditis elegans for target identification, validation, and drug screenings. In order to exploit the superb genetics and neurobiology of C. elegans for drug discovery, he cofounded in 1999 EleGene AG, (Martinsried, Germany).
