We propose to focus on deciphering the mechanistic underpinnings of intracellular replication, as a prominent source of pathogenesis. In particular, given its fundamental role in orchestrating central events to apicomplexan cell division, and flagellar assembly during sexual differentiation, we propose to focus on characterizing the apicomplexan centrosome. Recent findings suggest that apicomplexan centrioles are composed of a mixture of conserved and unique proteins. The latter remain largely unexplored and represent a possible rich source of drugable targets.
This project will be carried out in collaboration among three laboratories (Francia, Gissot and Bastin) with complementary technical and scientific expertise. The Francia laboratory at the Institut Pasteur Montevideo will perform molecular biology and genetic manipulation of T. gondii, generating the parasite cell lines necessary for launching this project. Maria Eugenia Francia is the PI of the project. The Gissot laboratory at the Institut Pasteur in Lille has extensive expertise on proteome and phospho-proteome analysis, invaluable skills for the advancement of this project. Finally, the Bastin Laboratory at the Institut Pasteur Paris has unparalleled knowledge on centrosome biology and experience in the use of advanced microscopy techniques such as super-resolution, photo-bleaching and electron microscopy to
approach flagellar biology related questions. These skills will be extensively exploited for the completion of this project.