Structural Analysis of Adenovirus Binding to Integrins (University of Tübingen) - (ViBrANT ITN)

Available at Faculty of Science and Faculty of Medicine, University of Tübingen (Germany)
Supervisor: Prof. Thilo Stehle
Location: Faculty of Science and Faculty of Medicine, Interfaculty Institute of Biochemistry (IFIB), University of Tübingen (Germany)

Background: Viruses use highly specific recognition processes to engage the target cell. The initial interaction between a viral capsid protein and the cell determines cell and host tropism as well as pathogenicity of a virus, and it often triggers and enables subsequent interactions that then allow the virus to enter the cell. Adenoviruses are established human pathogens that can cause a variety of serious diseases and are also of interest for gene delivery purposes as they are able to easily package and deliver foreign genomes to a target cell. While the structural basis of adenovirus binding to its protein receptors CAR and CD46 has been established, much less is known about the interactions of some of these virus strains with glycan receptors. In addition, all adenoviruses use integrin receptors for entry, and the structural basis of this interaction is entirely unknown. It is clear, however, that understanding the rules that allow adenoviruses to engage these attachment and entry receptors will greatly facilitate the use of these particles for targeting specific cell types, such as certain tumor cells that for example express high levels of specific glycan receptors.

Aim of project: The predominant aim of this PhD project is to investigate structural aspects of the interactions of adenoviruses with both glycan and integrin receptors. To achieve this, the relevant recombinantly expressed virus proteins (fiber, penton) will be complex with their respective receptors and the structures will be solved by X-ray crystallography in combination with additional biophysical approaches that can serve to support the observed interactions. The interactions will also be probed with site-directed mutagenesis to validate the observed contacts. Successful candidates should therefore have had some training in cloning and protein expression, as well as protein biochemistry.

Requirements: We are looking for motivated students with a Master’s degree in biology or biochemistry and some experience with cloning, expression and purification of proteins. Experience with biophysical and biochemical techniques to study protein structure and folding will be an advantage. Candidates must comply with both EU and the University of Tübingen eligibility criteria.
Further details on this project are available from Professor Thilo Stehle ([Email Address Removed]). Further details about the University of Tübingen, the Interfaculty Institute of Biochemistry and the research group are available at www.ifib.uni-tuebingen.de.