This PhD project is from the German-Israeli Helmholtz Research School in Cancer Biology, a joint PhD training initiative of the German Cancer Research Center and the Weizmann Institute of Science in Rehovot, Israel.
The successful candidate will be required to spend 6-12 months during their PhD working at the Weizmann Institute (in the laboratory of our collaborator, Prof. Joel L. Sussman). For further information about the Research School, please refer to the website: https://www.dkfz.de/en/phd-program/GIHRS.html Immunocompromised patients have an increased risk of norovirus infections and the disease can become chronic, lasting weeks to years. Furthermore, it was found that immunocompromised patients with chronic norovirus infections could generate genetic and antigenic variant viruses, suggesting a mechanism by which the virus could escape the host immune responses. The X-ray crystal structure of the prototype norovirus particle identified two domains, shell (S) and protruding (P) domains. Recently, it was found that the P domain interacts with polymorphic human histo-blood group antigens (HBGAs) and this interaction appears to be important for virus entry. The goal of this proposal is to better understand norovirus evolution in immunocompromised patients with chronic norovirus infections. We will concentrate on the RdRp and capsid genes, since these are important targets for antiviral development. The project has a number of aims: Determine the full-length genome sequences from norovirus isolates from chronically infected patients and describe the genetic changes over time • Express the variant capsid genes in insect cells and determine the antigenic changes among different variant viruses • Express the variant RdRp gene and capsid P domains in E. coli and determine their X-ray crystal structures • Compare the HBGA binding profiles among the variant P domains using X-ray crystallography • Investigate the enzymatic activities among the variant RdRps • Develop a virus-tracking system and observe the differences among the va-riant VLPs and their attachment/ entry to culture cells Your profile: • Experience in standard biochemical and molecular biology techniques as well as microbiology/ bacterial culture techniques is required • Experience in protein purification and some knowledge of X-ray crystallogra-phy is desirable • The successful candidate will be required to spend 6-12 months during their PhD working at the Weizmann Institute Duration: The position is limited for 3 years. Contact: [email protected]
