Maryse LEBRUN

Information

Scientific interests and projects

We are interested in the cellular and molecular mechanisms that enable apicomplexan parasites to infect and develop inside their host. The phylum Apicomplexa comprises single-celled eukaryotic parasites. They are important pathogens of humans and domestic animals. It includes Plasmodium spp. the causative agent of malaria, responsible for almost half million human deaths per year. 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 important discoveries to the malaria parasite. We use a broad array of cell biological and biochemical approaches, as well as cutting-edge molecular genetics and genome editing.

The M. Lebrun group explores i) the structure/function of proteins constituting the moving junction, a key structure formed during invasion of the host cell, ii) the mechanisms that trigger rhoptry exocytosis upon binding of the parasite to the host cell, iii) the fusion machinery of the rhoptry with the parasite plasma membrane, and iv) how rhoptry content is introduced in the host.

The group of S. Besteiro focuses on the contribution of an endosymbiotic organelle to the metabolism and survival of T. gondii in the context of both the acute and chronic phases of toxoplasmosis.

The group of M. Lamarque is interested in the functional characterization of selected P. falciparum phosphatases related to the invasion and egress mechanisms.

Top 5 publications of the last 5 years

1. Suarez C, Lentini G, Ramaswamy R, Maynadier M, Aquilini E, Berry-Sterkers L, Cipriano M, Chen AL, Bradley P, Striepen B, Boulanger MJ, Lebrun M. A lipid-binding protein mediates rhoptry discharge and invasion in Plasmodium falciparum and Toxoplasma gondii parasites. (2019) Nature Communications. 10(1):4041.

2. Paul AS, Miliu A, Paulo JA, Goldberg JM, Bonilla AM, Berry L, Seveno M, Braun-Breton C, Kosber AL, Elsworth B, Arriola JSN, Lebrun M, Gygi SP, Lamarque MH, Duraisingh MT. Co-option of Plasmodium falciparum PP1 for egress from host erythrocytes. Nature Communications. 2020. 11(1):3532.

3. Aquilini E, Cova MM, Mageswaran SK, Santos Pacheco ND, Sparvoli D, Penarete-Vargas DM, Najm R, Graindorge A, Suarez C, Maynadier M, Berry-Sterkers L, Urbach S, Ruga Fahy P, Guérin AN, Striepen B, Dubremetz JF, Chang Y-W, Turkewitz A, Lebrun M. An Alveolata secretory machinery adapted to parasite-host cell invasion. Nature Microbiology. 2021

4. Pamukcu S, Cerutti A, Bordat Y, Hem S, Rofidal V, Besteiro S. Differential contribution of two organelles of endosymbiotic origin to iron-sulfur cluster synthesis and overall fitness in Toxoplasma. PLoS Pathog. 2021 Nov 18;17(11):e1010096. doi: 10.1371/journal.ppat.1010096.

5. Sparvoli D, Delabre J, Penarete-Vargas DM, Kumar Mageswaran S, Tsypin LM, Heckendorn J, Theveny L, Maynadier M, Mendonça Cova M, Berry-Sterkers L, Guérin A, Dubremetz JF, Urbach S, Striepen B, Turkewitz AP, Chang YW, Lebrun M. An apical membrane complex for triggering rhoptry exocytosis and invasion in Toxoplasma. EMBO J. 2022 Nov 17;41(22):e111158.