Biography
Ivan Dikic grew up in Croatia, where he trained as a medical doctor. He obtained his PhD in molecular biology from the University of Zagreb while working under the supervision of Joseph Schlessinger at New York University Medical Center. He is currently a Professor at Goethe University Medical School and Director of the Buchmann Institute for Molecular Life Sciences in Frankfurt, Germany.
His research focuses on the role of ubiquitin (Ub), a small protein that is covalently attached to thousands of cellular proteins. His pioneering work explained how to decode the ubiquitin code in the cell. He showed that Ub acts as a multivalent cellular signal recognized by an expanding number of Ub-binding proteins that in turn translate this molecular signal into appropriate cellular phenotypes. His group identified several novel Ub-binding domains and used structural and functional studies to demonstrate their roles in the regulation of DNA repair, inflammation, receptor endocytosis, and proteasomal degradation. Most recently, they have described mechanisms by which linear ubiquitination can regulate the NF-kB pathway and apoptosis.
His recent recognitions and awards include the election in the German Academy Leopoldina (2010) and EMBO (2004), the ERC Advanced grant 2010, the German Cancer Prize 2010 and the Hans Krebs Prize 2010.
Seminar abstract
Ubiquitin acts as a cellular signal that is decoded by its receptors to control normal functioning of the cell via different linkage types. Using the different structural and biochemical properties of different ubiquitin chain linkages, we have developed fluorescence-based sensors to monitor real-time localization and dynamics of ubiquitination events in vivo. For example, linear chain-specific sensors labeled the ubiquitin coat surrounding cytosolic Salmonella and were also able to block TNF-induced NF-κB activation; whereas K63-sensors were enriched at DNA double strand breaks and depolarized mitochondria following Parkin recruitment.
In addition to sensors that detect linkage-specific ubiquitin chains, we have been exploring the fate of intracellular pathogens and how they are targeted by the host autophagy system. Removal of harmful protein aggregates, damaged organelles and microbes is mediated by autophagy, a process by which the cell sequesters cytosolic cargo and delivers it for degradation by the lysosome. Optineurin, a new autophagy receptor, together with p62 and NDP52, mediates selective autophagy of ubiquitin-coated cytosolic Salmonella enterica. The protein kinase TBK1 (TANK binding kinase 1) was shown to mediate phosphorylation of both LC3- and Ub-binding domains to ensure a rapid engulfment of cytosolic bacteria and efficient autophagic clearance.