BBB seminar: Oddmund Bakke
Protein sorting to the "Compartment for MHC-II Antigen Loading"
Division for Biochemistry and Molecular Biology, Department of Biomedicine, University of Bergen
The Invariant chain (Ii) is responsible for targeting MHC class II molecules to intracellular compartments for antigen loading and subsequent antigen presentation to CD4+ T cells. We also showed that Ii inhibits endocytic transport and increases the size of endosomes. In a cell-free assay we further found that expression of Ii increases endosomal fusion. Data from mutagenesis analysis and NMR-based structure calculations of the Ii cytoplasmic tail demonstrate that interactions between Ii cytoplasmic tails are essential for these events. Imaging of live cells using GFP-fusion proteins shows that it is the early endosomes that increase their homotypic fusion after Ii is induced. The combined data from live cells, cell-free assays and molecular dynamic simulations suggest that Ii molecules on different vesicles can promote docking and fusion and thereby control endosomal traffic of membrane proteins and endosomal content. We propose that this is the mechanism behind the formation of MHC-class II antigen loading compartments. To maintain the size of endosomes the fusion events have to be followed by fission events. Using a rapid spinning disc confocal on live cells, creating 4D images, we visualise live fusion and frequent fission events that support our model of a specific endocytic pathway of antigen processing and MHC class II antigen loading.
Oddmund Bakke, originally from Bergen, had a varied career: educated in biophysics at the NTH, Trondheim; radiation and particle physics research at CERN, Geneva; PhD from Trondheim; postdoc at the Brandeis University, Boston; biomedical research at SINTEF, Trondheim; postdoc at the EMBL, Heidelberg, working with Prof. Bernhard Dobberstein (1988-90); professor at the University of Oslo from 1991 and professor at the UiB from 2003.
Starting at the EMBL with a landmark paper in Cell, 1990, Oddmund Bakke's main research interest is the area of molecular immunology, in particular the intracellular mechanisms behind MHC class II antigen loading and antigen presentation. The approach is from the cell biology side, studying intracellular sorting mechanisms and protein-protein interactions and performing live cell imaging of the endocytic pathway using various fluorescent fusion proteins. Oddmund Bakke has published more than 100 scientific articles and book chapters in the different fields.