Introduction: Human noroviruses are constantly evolving through mutations in the capsid gene into genetically and antigenically distinct strains. The norovirus capsid protein is divided into a shell (S) domain and protruding (P) domain, the latter of which, is further subdivided into P1 and P2 subdomains. The capsid binds histo-blood group antigens (HBGAs) and this interaction is thought to be important for cell attachment. Our group has solved over 30 different P domain HBGA complex structures, including several that were previously unknown. We recently discovered that noroviruses have two additional HBGA pockets on the capsid. Taken together, our findings highlight the complexities of HBGA and norovirus binding interactions.
Purpose: We have several objectives in a DFG funded proposal in order to better understand HBGA interactions with human noroviruses. 1. Inhibition of the HBGA pocket with lead compounds 2. Rational design of monoclonal antibodies that block the HBGA pocket 3. HBGA interactions with novel noroviruses and other related viruses For this purpose, we would like someone with relevant experience in protein structural biology Requirements: • Experience in protein expression and purification (e.g., affinity, size-exclusion, ion-exchange, etc.) • Biochemical/biophysical characterization techniques (e.g., Western blot, light scattering, calorimetry, DLS) • Excellent knowledge and expertise in protein structural biology • Participation in all stages of the structure determination process from target selection through to model interpretation • Demonstrated independent thought/creativity in science. • Willingness to drive challenging scientific projects in an independent and creative manner Interested applicants should send CV and statement of interest to Grant Hansman: g.hans...@dkfz.de
