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Role of an aspartyl protease in maturation and trafficking of secreted proteins in Toxoplasma gondii Key words: Parasitology, Microbiology

Author Pierre-Mehdi HAMMOUDI
Director of thesis Dr. Dominique Soldati-Favre
Co-director of thesis Dr. Luis Lopez-Molina
Summary of thesis

The opportunistic pathogen Toxoplasma gondii infects a large range of nucleated cells where it replicates intracellularly within a parasitophorous vacuole (PV) surrounded by a membrane (PVM). Parasites constitutively secrete dense-granule proteins (GRAs) both into and beyond the PV which participate in remodelling of the PVM, recruitment of host organelles, neutralization of the host cellular defences, and subversion of host cell functioning. In addition, the GRAs critically contribute to cyst wall formation, a process that critically ensures parasite persistence and transmission. To act as effector molecules, some of the GRAs must be translocated across the PVM. Within the related apicomplexan parasite P. falciparum, a repertoire of proteins exported beyond the PVM contain a motif cleaved by a specific protease, Plasmepsin V. Examination of the repertoire of GRAs in T. gondii revealed that some proteins exhibit such export-like motifs suggestive of protease involvement. During the first part of my PhD, I have functionally characterized the related aspartyl protease 5 (TgASP5) in both virulent and persistent T. gondii strains, and have investigated the phenotypic consequences of its deletion in the context of overall parasite biology, its intracellular niche, the infected host cells and the murine model. Our future work will aim at characterize novel ASP5 substrates recently identified and widen our investigations on the study of the persistent stage of the parasite.

Administrative delay for the defence 2017 (started in September 2013)