DC2: Characterization of pathogen strain diversity and host interactions by proteomics mass spectrometry

The PhD candidate will study bacterial cell-wall and secreted virulence factors involved in host adhesion and immune evasion. The work centers on virulence factors from Staphylococcus aureus and Pseudomonas aeruginosa, which are ESKAPE pathogens notorious for their biofilm-forming capabilities and their emerging multidrug resistance. In this project, you will identify and characterize the host interactions of these species using methods in quantitative and structural proteomics. The research questions span from characterizing the interactomes of intact bacteria to that of isolated virulence factors and their domains. Using infection assays, you will establish the importance of selected adhesins in different stages of the infection process and identify host cell receptors. The work will be done in close collaboration with groups in the network interested in cellular models for host adhesion, biofilm formation and bioinformatics. The position offers the opportunity of internships with both academic and industrial partners, including the characterization of pathogen adhesion to host cells using a vasculature-on-chip model, and the adhesion of biofilm forming bacteria to biomaterials.

Methods will include quantitative affinity-purification and surface adsorption mass spectrometry using isolated virulence factors and intact bacteria, respectively. Structural proteomics (cross-linking and hydrogen-deuterium exchange mass spectrometry) will be used to map the host-pathogen interface at high-resolution, optionally followed by structural determination of the complexes using cryo-EM. These methods are complemented with bioinformatics and structural modeling and docking. Other methods applied include standard methods in molecular microbiology, as well as cellular infection and biophysical adhesion assays.