Infectious mechanisms and control of emerging zoonoses
The research conducted by the MOCA team focuses on studying the molecular and cellular mechanisms involved in host-pathogen interactions with the aim of developing innovative anti-infective strategies.
Objectives
Emerging zoonoses are shaping future health crises. In the southwestern Indian Ocean, outbreaks are a recurring phenomenon. Our ambition is to understand in order to respond more effectively, anticipate by accelerating knowledge acquisition outside of emergency periods, and develop innovative prophylactic and biotherapeutic countermeasures upstream disease outbreaks. This theme combines mechanistic research and anti-infective innovation. We decipher the molecular and cellular interactions between zoonotic agents, human hosts, and invertebrate vectors, integrating the determinants of transmission and pathogenicity in a context of global change. This approach allows us to tune the development of natural antimicrobial compounds towards relevant biological targets, at both pathogen and host levels. Our work covers a broad spectrum of viral and bacterial agents (leptospires, coronaviruses and arboviruses: ZIKV, DENV, CHIKV) and enables us to link virulence, cellular and tissue tropism, replication dynamics, and the severity of clinical manifestations.
Approaches
We use a range of complementary experimental models and approaches: infectious clones and reverse genetics, regional clinical isolates and hospital cohorts, human cell lines as well as vertebrate and invertebrate in vivo models. This integrative strategy allows us to identify virulence determinants, disentangle adaptation mechanisms involved in host changes, highlight immune escape strategies and metabolic reprogramming that determine the outcome of acute infection in humans. Pharmacognosy is a pillar of our strategy: we explore the plant biodiversity of the southwestern Indian ocean and the Indo-Pacific as a reservoir of bioactive molecules. By combining chemoinformatics with in vitro and in vivo screening, we identify antiviral and antibacterial compounds targeting the pathogen and/or host, for their development and transfer.
Several types of cultured cell lines are routinely used to characterize the interactions of the infectious agent with its host and to identify the metabolic pathways affected by the infection. In vivo, we are currently developing a new viral infection model based on the use of Drosophila as a host with the insect's intestine as the target tissue of the infectious agent. Soon, we will have a high-throughput screening platform for the search for natural substances active against medically relevant viruses. The isolation and characterization of antiviral molecules from plant extracts are carried out through a multidisciplinary approach at the interface of phytochemistry, virology, and chemoinformatics (molecular networks).
