Host cell invasion and intracellular survival in apicomplexan parasites

 


Carte de viste 2

 

 

Dr. Lebrun completed a PhD at the Institut National de la Recherche Agronomique in Tours, working on molecular mechanisms of cadmium resistance in the pathogenic bacteria Listeria monocytogenes. After a post-Doc in the Laboratory of Pascale Cossart at the Pasteur Institute on invasion of Listeria, her interest shifted to the mechanisms of invasion of protozoan parasite Toxoplasma gondii, a prominent cause of human congenital infections. She obtained in 2002 a permanent position as INSERM Permanent Scientist and then in 2009 as INSERM Research Director, to work at the University of Montpellier on the mechanisms of host cell invasion and intracellular replication of Toxoplasma and Plasmodium.

 

LEBRUN'S LAB RESEARCH INTERESTS.


We are interested in the cellular and molecular mechanisms that enable apicomplexan parasites to infect and develop inside host. Apicomplexan are single-celled eukaryotes parasites. They are important pathogens of humans and domestic animals. They include Plasmodium spp. the causative agent of malaria. Malaria is responsible for almost half million human deaths per year and increasing drug-resistance is a considerable concern. It also includes Toxoplasma, a prominent cause of human congenital infections and Cryptosporidium, a leading cause of severe diarrhea and mortality in infants. No vaccine currently exists against these parasites.
The objectives of our team are to decipher cellular and molecular features related to two essential parasitic functions: host cell invasion and intracellular replication, with the aim of identifying novel therapeutic strategies. Our research is mainly focused on T. gondii, which is a relevant model for many features conserved throughout the phylum. We then extend our most important discoveries to the malaria parasite. We use a broad array of cell biological and biochemical approaches, as well as state-of the art molecular genetics and genome editing.


Our team has received a team label from ‘Fondation pour la Recherche Médicale’ (‘Medical Research Foundation’ – FRM) both in 2013 and in 2016

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Group leader: Maryse LEBRUN

The Apicomplexa phylum is defined by the presence of an apical complex of organelles comprising two specific secretory granules called micronemes and rhoptries, which sequentially release their contents during invasion. Microneme proteins contribute to motility, attachment and invasion, while rhoptry proteins contribute to both invasion and subsequent manipulation of host cell functions after the parasites have established themselves in their host cells. Our research is focused on the formation of a structure (the moving junction) which is essential for host cell invasion in both Toxoplasma and Plasmodium, and which depends on the cooperation between microneme and rhoptry proteins. We are also interested on the mechanism of secretion of rhoptries, which remains a major conundrum in the field.

 

Goup leader: Sébastien BESTEIRO

Autophagy is a catabolic pathway that is highly conserved among eukaryotes and permits the degradation of cellular material. We are interested in elucidating the physiological roles of parasite autophagy in the context of acute and chronic toxoplasmosis, and identifying which stimuli are responsible for inducing parasite autophagy, as well as mechanisms regulating the pathway. We discovered and are currently exploring, original apicoplast-related functions for autophagy proteins in Toxoplasma. The apicoplast is an important organelle for parasite metabolism, and we are also investigating its contribution to different developmental stages of the parasite.

 

Group leader: Mauld LAMARQUE


Despite growing evidence regarding the importance of kinases throughout the life cycle of P. falciparum and T. gondii and the fact that global phosphoproteomic analyses revealed that almost half of the predicted proteome is being phosphorylated, the biological significance of the phosphorylation/dephosphorylation event remain largely a black box. In this context, we aim at fully characterizing P. falciparum phosphatases that play an important role during its intra-erythrocytic development, with a particular interest on the invasion and egress mechanisms.