Project description
Variations in antiviral responses
The type I interferon (IFN-I) system is a crucial part of the body's innate immune response against viral infections. It encompasses a group of cytokines, including interferons alpha and beta, which are produced by host cells in response to viral pathogens and promote the activation of immune cells. Funded by the Marie Skłodowska-Curie Actions programme, the VARIFN project will employ a systems immunology approach to understand the variables that determine the IFN-I response. Researchers will use a large cohort of donors and evaluate the influence of microbiome, immune cell, and plasma protein composition on immune responses. The study will reveal new regulators of the IFN-I system and pave the way towards enhancing antiviral immunity.
Objective
Both antiviral immunity and susceptibility to viral infections are remarkably variable. Factors such as older age, increased body mass index, and male sex can increase the risk of developing severe viral disease, yet the impact of these features on antiviral immunity, particularly the type I interferon system (IFN-I), is not understood. Here we propose to use a systems immunology approach to identify features that influence IFN-I responses and understand their impact on infection susceptibility. We will use datasets and samples from the Milieu Interieur (MI) cohort of 1000 donors consisting 500 males and 500 females aged 20-69 years old. Using Simoa digital ELISAs, we have quantified IFN-I (IFNa and IFNb) in the supernatants of whole blood from the 1000 donors that was stimulated ex vivo with 7 agonists that activate the IFN-I system. Preliminary analysis of these results shows interesting age and sex differences in the IFN-I response. We will integrate the IFN-I cytokine data with existing demographic, microbiome, immune cell phenotyping and plasma protein data from the cohort and determine their associations with IFN-I levels. To investigate sex differences in IFN-I we will quantify sex hormones in the plasma of the 1000 donors. We will perform RNA-sequencing on IFNa-stimulated whole blood on a subset (n=200) of the donors to investigate the factors that shape the response to IFNa itself. We will perform genome wide association studies of the IFN-I response in the cohort to identify variants that influence IFN-I production using SNP genotyping data from MI. To determine the impact of these features on IFN-I and influenza infectivity in vitro, we will develop an organ on chip model encompassing features that we find to be associated with IFN-I levels in MI. Results from this project will identify novel regulators of IFN-I and shed light on new strategies to boost the antiviral response to better protect against viral infection.
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 biochemistry biomolecules proteins
- medical and health sciences health sciences infectious diseases RNA viruses influenza
- medical and health sciences basic medicine immunology
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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)
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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
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2023-PF-01
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75724 Paris
France
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