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Subversion of phagocyte functions by the intracellular pathogen Legionella.
Legionella pneumophila is a ubiquitous environmental bacterium that replicates within protozoa, including the genetically tractable social amoeba Dictyostelium . Upon inhalation of contaminated aerosols, the opportunistic pathogen grows within macrophages in the lung and causes a severe pneumonia termed Legionnaires’ disease. L. pneumophila employs a conserved mechanism to grow in amoebae and macrophages by forming a unique Legionella -containing vacuole (LCV). LCV formation is a complex and robust process involving a bacterial type IV secretion system and ca. 300 (!) different secreted effector proteins, which subvert in an ill-defined manner host cell signaling and vesicle trafficking pathways.
Current research in our laboratory focuses on (i) the molecular mechanism of secreted L. pneumophila effector proteins, (ii) proteome analysis of purified LCVs, (iii) bacterial phenotypic heterogeneity, and (iv) signal transduction and gene regulation by α-hydroxyketone compounds.
Within this framework, the specific Ph.D. project will contribute to a comprehensive understanding of subversion of phagocyte functions by L. pneumophila . To analyze pathogen-host cell interactions, the Ph.D. student will use a broad range of techniques in the disciplines Bacteriology (handling of BSL-2 pathogens), Cellular Microbiology (infection, replication and cytotoxicity assays), Cell Biology (fluorescence microscopy, flow cytometry, RNA interference), Biochemistry (protein-protein and protein-lipid interactions, LCV isolation) and Molecular Biology (mutagenesis, gene expression). References.
Finsel, I. & Hilbi, H. (2015) Formation of a pathogen vacuole according to Legionella pneumophila : how to kill one bird with many stones. Cell. Microbiol. 17 : 935-950.
Personnic, N., Bärlocher, K., Finsel, I. & Hilbi, H. (2016) Subversion of retrograde trafficking by translocated pathogen effectors. Trends Microbiol. 24 : 450-462.
Hochstrasser, R. & Hilbi, H. (2017) Intra-species and inter-kingdom signaling of Legionella pneumophila . Front. Microbiol. 8 : 79.
Highly motivated individuals with an interest and background in Molecular/Cellular Microbiology, Cell Biology, Biochemistry or a related area are invited to apply. For further information about the position please contact Prof. Hubert Hilbi (email@example.com) or Dr. Nicolas Personnic (firstname.lastname@example.org) and visit our website at: ?url=http%3A%2F%2Fwww.imm.uzh.ch%2Fresearch%2Fexperimental%2FHilbi.html.&module=jobs&id=118528" target="_blank" rel="nofollow">www.imm.uzh.ch/research/experimental/Hilbi.html.
An exciting and challenging 4 year Ph.D. project in a supportive environment with salary according to SNF scale.
Please send applications as a single PDF file to Prof. Dr. Hubert Hilbi (hilbiimm.uzh.ch).