A PhD position is available at the Freie Universität Berlin, Department of Biochemistry to analyse HLA-DM catalyzed peptide loading of MHC class II proteins by NMR spectroscopy and other biophysical methods.
Nascent MHC II proteins are preloaded with self-peptides. In the endolysosomal compartment the exchange of the self-peptide for higher affine antigenic peptide is catalyzed by the MHC-like molecule HLA-DM. This leads to immunogenic MHC II-peptide complexes that are presented on the cell surface for T-cell recognition.
Within an interdisciplinary team including immunologists, crystallographers and molecular modellers we gained critical insights into MHC peptide loading by biochemical and spectroscopical analysis of the reaction over the past years (Günther et al., PNAS 2010; Schlundt et al., Angewandte Chemie 2009), however the precise mode of action of the HLA-DM catalyzed peptide exchange is still missing. Your task will be to target the mechanism of HLA-DM catalysis. This involves the expression and purification of MHC class II proteins (a heterodimer of ~46kD) based on working protocols integrating different labeling schemes for NMR analysis. The high molecular weight and seemingly short half-live of the MHC II - HLA-DM complex is likely to involve the design and purification of modified constructs as well as more sophisticated NMR methods including H/D exchange and relaxation dispersion experiments.
We are looking for candidates with a strong interest in structural biology and ideally with experience in protein purification and a basic knowledge of protein NMR spectroscopy.
Funding is available for a minimum of three years.
For application please contact:
Prof. Dr. Christian Freund
Freie Universität Berlin
Thielallee 63
14195 Berlin
freund@fmp-berlin.de or chfreund@zedat.fu-berlin.de
