Project description
Tracing the dengue virus evolution
Dengue virus (DENV) is the most prevalent arbovirus worldwide. Its rapid evolution complicates efforts to control it. The non-structural protein 1 (NS1) plays a crucial role in its replication and transmission, yet its evolutionary constraints remain poorly understood. With the support of the Marie Skłodowska-Curie Actions programme, the MOSAIC project will investigate the impact of NS1 variants on DENV infection through deep mutational scanning. It will create diverse viral populations to study their impact on mosquito and human cell lines, uncovering host-specific selective pressures. In vivo mosquito infections will help map NS1 variant distribution and the mosquito transcriptome at single-cell resolution. The project will elucidate DENV evolution, transmission bottlenecks and interactions with mosquito immunity.
Objective
Dengue virus (DENV) is the most prevalent arbovirus worldwide and its ability to rapidly evolve and adapt complicates efforts to control its spread. A key factor in the replication cycle of DENV is the multifunctional non-structural protein 1 (NS1), which is involved in viral replication, transmission, and pathogenesis. Despite its importance, the evolutionary constraints and host-specific functions of NS1 remain poorly understood.
To address this gap, I propose MOSAIC: a comprehensive approach to map the impact of NS1 variants on DENV infection. Using deep mutational scanning (DMS), I will generate diverse viral populations to assess the fitness effects of DENV NS1 variants in mosquito and human cell lines, uncovering host-specific selective pressures. These diverse populations will then be used for in vivo mosquito infection to generate a detailed atlas of NS1 variant distribution across mosquito cells and map the corresponding mosquito transcriptome at single-cell resolution. By combining my expertise in virus evolution with the leading work of the host lab on insect immunity, MOSAIC will uniquely integrate DMS and single-cell transcriptomics, establishing the foundation for novel ways to understand virus evolution at high resolution.
MOSAIC will reveal insights into the evolutionary constraints of DENV NS1, identify transmission bottlenecks in distinct mosquito organs and cell types, and explore the interaction between DENV and mosquito immunity. This work will advance our understanding of flavivirus biology and host-virus interactions from a novel perspective, informing the development of new vector control strategies, vaccines, and therapeutics to combat DENV and other arboviral diseases in line with EU global health priorities. Finally, MOSAIC will provide me with multidisciplinary training in advanced genomics, vector biology and bioinformatics, strengthening my expertise in infectious disease research and preparing me to become an independent researcher.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences microbiology virology
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics RNA transcriptomes
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
- natural sciences biological sciences zoology invertebrate zoology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2024-PF-01
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
75724 Paris
France
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.