Lead


Lay summary
Lead: The Apicomplexa groups obligate intracellular pathogens responsible for severe diseases such as malaria and toxoplasmosis. This project aims at studying the molecular mechanisms underlining parasite lytic cycle, which involves active host cell entry, intracellular replication and egress from host cells.Résumé:Gliding motility is a unique attribute of the phylum Apicomplexa, which is crucial for parasite migration across biological barriers, host cell invasion and egress from infected cells. Timing, duration and orientation of gliding motility are tightly regulated by i) two formins that spatially control actin filaments polymerization ii) assembly and disassembly of myosin motor complexes, which is governed by posttranslational modifications resulting from a calcium-dependent signaling cascade, Host cell invasion involves the recognition host cell receptors by specialized parasite adhesins, followed by disengagement of these adhesins through the action of parasite rhomboid proteases. The process culminates with a switching mechanism from the invasive- to the replicative-mode. There a complex spatial and temporal interplay between the components of host cell recognition, gliding machinery, and parasite replication.But: Our studies focus on the regulators of actin dynamics, the myosin motors, the transmembrane micronemal proteins complexes and the proteases involved in their processing. The aim is to elucidate how these classes of proteins are connected together and act in concert to control invasion, replication and egress in apicomplexans. Ultimately, the outcome of those investigations should lead to the identification of novel targets for intervention against these lethal or debilitating pathogens.Signification: Apicomplexa are eukaryotic organisms posing serious public health concerns and veterinary problems. They have evolved a broad variety of highly sophisticated strategies evolved to subvert host processes in order to maximize access to nutrients, assure dissemination and transmission, neutralize host defenses, and avoid destruction. A fundamental understanding of the basic molecular mechanisms of parasitism is a prerequisite to defeat them.