MOlecular and Cellular mechanisms of infectious Agents

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.

The activities of the MOCA team include four research questions:
1. The identification of determinants of the infectious agent pathogenicity;
2. The understanding of physiopathological processes as consequences of infection;
3. The development of pathogen screening tools and infection diagnostics;
4. The anti-infective strategies based on the chemical and biological characterization of natural substances from plant biodiversity that are active against the infectious agent, and the design of vaccines based on the principle of attenuating its pathogenicity.

An expertise on the study of emerging pathogens interacting with their hosts

Our study models are primarily emerging RNA viruses, including arboviruses such as dengue virus, Zika virus, and more recently Usutu virus, as well as the SARS-CoV-2 coronavirus. Experimental approaches rely on cellular and animal models (both vertebrates and invertebrates). Our research aims at characterizing (1) the molecular determinants contributing to the pathogenicity of the infectious agent and (2) host-pathogen interactions, with particular attention to changes in cellular metabolism in infected target tissues, innate anti-infectious immunity, mechanisms of cell death triggered in response to infection, and countermeasures developed by the pathogen to circumvent host defense pathways to its advantage. Data on host-pathogen interactions are used for the development of effective anti-infectious strategies, relying on the development of vaccine candidates and the discovery of natural substances from plant biodiversity that have been identified for their ability to inhibit infectious process.

Developping technologies for the study of emerging pathogens

The implementation of research questions requires, especially when the studied infectious agent has been poorly characterized so far, the availability of efficient detection tools and relevant experimental models to study its pathogenicity. For arboviruses, we have reverse genetics technology to generate viral molecular clones associated with reporter systems (GFP, Luc, etc.). They allow the identification of virulence factors or the development of attenuated viruses as vaccine candidates. We are also developing systems allowing stable expression of recombinant viral proteins characterized for their biological properties, outside the context of infection, but which can also serve as tools for the development of diagnostic kits based on nanotechnologies.

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).

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