Title: Coordination of post-translational modifications in human protein interaction network
Lecturer: Ulrich Stelzl, Network Pharmacology, Insitute of Pharmaceutical Sciences, Karl-Franzens University Graz
Abstract: Comprehensive protein interaction networks are prerequisite for a better understanding of complex genotype to phenotype relationships. Post – translational modifications (PTMs) regulate protein activity, stability and protein interaction (PPI) profiles critical for cellular functioning. In combined experimental and computational approaches, we want to elucidate the role of post – translational protein modifications, such as phosphorylation, for these dynamic processes and investigate how the large number of changing PTMs is coordinated in cellular protein networks and likewise how PTMs may modulate protein – protein interaction networks. We identified hundreds of protein complexes that selectively accumulate different PTMs i.e. phosphorylation, acetylation and ubiquitination. Also protein regions of very high PTM densities, termed PTMi spots, were characterized and show domain – like features. The analysis of phosphorylation – dependent interactions provides clues on how these PPIs are dynamically and spatially constrained to separate simultaneously triggered growth signals which are often altered in oncogenic conditions. Our data indicate coordinated targeting of specific molecular functions via PTMs at different levels emphasizing a protein network approach as requisite to better understand modification impact on cellular signaling and cancer phenotypes.
Short bio: Ulrich Stelzl studied Chemistry/Biochemistry at the TU Vienna and ETH Zürich. His PhD thesis (MPIMG, Berlin) and first PostDoc (MSKCC, New York) addressed detailed biochemical questions of RNA-protein recognition, such as the assembly and dynamics of ribonucleo-protein complexes in gene expression and regulation. Then at the MDC Berlin, Ulrich Stelzl contributed significantly to well recognized protein-protein interaction (PPI) studies such as the generation and analysis of the first human proteome scale PPI networks or the development of an empirical framework for human interactome mapping. The importance of the work and its interdisciplinary character was recognized by the Erwin Schrödinger Price 2008 of the German Helmholtz Society. From 2007 on, Ulrich Stelzl headed the Max-Planck Research Group “Molecular Interaction Networks” at the MPIMG, Berlin and joined recently the Department of Pharmaceutical Sciences of the University of Graz.