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© François Rodhain
Plasmodium malariae (un des quatre hématozoaires qui parasitent l'homme), agent du paludisme, dans un frottis de sang humain. Stade trophozoïte. Coloration de May-Grünwald Giemsa.

About

The blood stage of the malaria parasite life cycle is responsible for all the clinical symptoms of malaria. During the blood stage plasmodium merozoites invade and multiply within red blood cells (RBCs). We are interested in understanding the receptor-ligand interactions that mediate the invasion process. Understanding the key receptor-ligand interactions involved in host cell invasion may open new paths for the development of intervention strategies that inhibit red cell invasion and block blood stage parasite growth. We also study the process by which newly developed merozoites in a blood stage schizont egress following complete development.

Parasite proteins involved in red cell invasion and egress: The invasion of red cells by malaria parasites is a complex process that involves a series of specific molecular interactions between parasite proteins and red cell receptors that mediate different steps in the invasion process. We study two families of parasite proteins, namely, the erythrocyte binding antigen family, which includes P. falciparum EBA175 and P. vivax Duffy binding protein (PvDBP), and the P. vivax reticulocyte binding protein family (PvRBPs) and their P. falciparum homologs (PfRH1, PfRH2a/b and PfRH5). Structure function studies are used to map functional receptor-binding sites within these parasite proteins and antibodies to these binding domains are tested for inhibition of P. falciparum growth in vitro individually and in combination to identify parasite antigens that could be included in a blood stage vaccine for P. falciparum malaria.

Signaling pathways involved in regulating red cell invasion and merozoite egress. A number of the parasite proteins that mediate key interactions with host receptors to mediate invasion are initially expressed in internal apical organelles referred to as micronemes and rhoptries and are exported to the apical surface of merozoites during the invasion process. We are interested in identifying the signals and understanding the signaling pathways that regulate the secretion of microneme and rhoptry proteins during invasion. We use molecular genetic, biochemical as well as phosphoproteomic approaches to define the signaling pathways that trigger microneme and rhoptry secretion. We are also interested in understanding the signals and signaling pathways that regulate egress of merozoites from mature schizonts. We have demonstrated that a number of key effectors that play a role in egress are localized in apical organelles such as micronemes and exonemes. The secretion of these organelles is triggered by rise in internal Ca2+. Understanding the signaling pathways that mediate these critical steps in the parasite life cycle can open new avenues for the development of novel targets for drugs that inhibit parasite growth by blocking apical organelle release during egress or invasion.

Malaria vaccine development. We use our understanding of the key receptor-ligand interactions involved in RBC invasion by Plasmodium merozoites for the development of recombinant vaccines that target blood stage parasites. We are developing recombinant vaccines based on functional receptor-binding domains of parasite proteins such as P. vivax Duffy binding protein (PvDBP), P.vivax reticulocyte binding proteins, P. falciparum EBA175 and PfRH5 that mediate critical interactions with host receptors to mediate invasion. Combinations of parasite ligands that yield high rates of growth inhibition due to synergy are identified for development as multi-component vaccine candidates. Efforts are also underway to identify novel delivery strategies that elicit robust immune responses against such multi-component vaccines. These include exploring novel viral vectors, protein conjugation technologies and novel nano-particles formulated with potent adjuvants.

Former Members

2000
2000
Name
Position
2014
2015
Marie Demeslay-Gougam
Administrative Assistant
2014
2016
Shailja Singh
Research Fellow
2014
2019
Pallavi Singh
PhD Student
2014
2022
Micheline Guillotte-Blisnick
Engineer
2015
2016
Cidalia Da Agra
Administrative Assistant
2015
2018
Aditi Alaganan
Post-doc
2016
2016
Amandine Aoufoussi
Undergraduate Student
2016
2017
Aida Valmaseda Freixa
PhD Student OREX
2016
2018
Aneesh Vijayan
Post-doc
2016
2019
Kunal More
Post-doc
2016
2022
Matthias Wagner
PhD Student PPU
2017
2017
Candice Verbrugghe
Undergraduate Student
2017
2017
Swati Garg
OREX Post-doc
2017
2017
Emilia McLaughin
Bachelor degree student
2017
2018
Undina Guillerm
Engineer
2019
2019
Mona Nivard
Undergraduate Student
2019
2019
Neele Wewer
Master 2 student
2019
2019
Kabir Sodhi
Undergraduate student
2019
2022
Dipto Sinha
Research fellow
2022
2022
Nelliane Mouzou
Lab. Technician student
2022
2022
Emilie Attali-Bonheur
High school student
2023
2023
Maya Bottero
High school student
2023
2023
Florian Westrelin
Master 2 student
2023
2023
Violette Boudsocq
Master 2 student
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Courses

Malaria MOOC

The MOOC provides an overview of malaria today, from the cellular biology of the parasite to treatments, from immune response to control and elimination strategies. >>Register here << Malaria is an ancient disease that […]

2022-10-11 09:00:00 2022-11-30 19:00:00 Europe/Paris Malaria MOOC The MOOC provides an overview of malaria today, from the cellular biology of the parasite to treatments, from immune response to control and elimination strategies. >>Register here << Malaria is an ancient disease that […]

Projects

Transversal Project

Publications

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Contact

Phone : 01 40 61 39 91 (assistant) Email : chetan.chitnis@pasteur.fr / maryse.brandt@pasteur.fr (assistant) Address Sergent Building n° 25, 25-28 Rue du Docteur Roux 75015, Paris France

5th floor, left side, offices n° 06A and 06.