Description du projet
De nouvelles stratégies de lutte contre la dengue
Les maladies infectieuses émergentes, exacerbées par des facteurs tels que le réchauffement planétaire et la mondialisation, constituent une menace croissante pour la santé mondiale. La dengue, par exemple, transmise par les moustiques Aedes aegypti, infecte des centaines de millions de personnes chaque année. Dans ce contexte, le projet DENVMosSusceptible financé par le MSCA cherche à comprendre pourquoi certaines populations de moustiques véhiculent le virus de la dengue, alors que d’autres pas. S’appuyant sur des techniques de pointe telles que la transcriptomique et la métabolomique à cellule unique, les chercheurs analyseront les réponses cellulaires dans les organes critiques du moustique: l’intestin moyen (point d’entrée du virus) et le corps adipeux (régulateur du métabolisme). En examinant les modèles d’expression génétique et les voies métaboliques, le projet entend identifier les facteurs déterminant la prédisposition au niveau cellulaire.
Objectif
Emerging infectious diseases represent a global health problem, as demonstrated by the Covid-19 pandemic. Among them, viral pathogens transmitted by mosquitoes represent a growing threat to human health, due to global warming and globalization. For example, Aedes aegypti mosquitoes are the main vectors of dengue viruses that infect 400 million people annually. However, major knowledge gaps remain in our understanding of interactions between mosquitoes and viruses. For example, the mechanisms underlying natural variation in susceptibility to viral infection between different mosquito populations remain mostly unknown. My project aims to address this question using novel methods combining single-cell transcriptomics and metabolomics approaches. First, I will identify Ae. aegypti mosquito populations that are highly or poorly susceptible to infection with dengue viruses. Next, I will analyze infection dynamics in key mosquito organs: the mosquito midgut, which is the entry point for the virus, and the fat body which regulates metabolism. I will analyze their response to virus infection using single-cell transcriptomics and metabolomics. A joint “multi-omics” analysis of both datasets will describe, for the first time, the metabolic functions of different cellular subpopulations of the mosquito midgut and fat body upon dengue infection. It will reveal the metabolic pathways and gene expression patterns that are associated with susceptibility towards virus infection at the cellular level. Finally, the contribution of these candidate genes and metabolites to susceptibility or resistance to infection will be validated using functional assays (e.g. chemical inhibition, gene knockdown) in vivo. This project will address an important knowledge gap in virus-mosquito interactions by revealing metabolic factors underlying susceptibility towards dengue virus infections. These results might contribute to the development of innovative disease-control strategies in the future.
Champ scientifique
- natural sciencesbiological sciencesmicrobiologyvirology
- medical and health scienceshealth sciencespublic healthepidemiologypandemics
- medical and health scienceshealth sciencesinfectious diseasesRNA virusescoronaviruses
- social sciencessociologyglobalization
- natural sciencesbiological scienceszoologyinvertebrate zoology
Mots‑clés
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Régime de financement
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinateur
75724 Paris
France