Objective
Cell-autonomous innate immunity is the first line of defense against pathogens and is crucial in infections, viral cross-species transmissions and autoimmunity. In mammals, it is notably composed of proteins from the interferon pathway inhibiting viruses within infected cells. In turn, viruses evade or antagonize immunity, leading to virus-host evolutionary arms-races. Beyond classic adaptation by site-specific positive selection, we discovered cases of gene duplications with divergence in gene expression and sequence, including by protein domain rearrangements, that appear adaptive in Myotis bats. I thus hypothesize that recurrent gene duplications and domain rearrangements represent overlooked biological principles in the diversification of mammalian innate immunity, enabling hosts to keep up against rapidly evolving viruses. I further hypothesize that we can use these evolutionary cues to distinctively discover novel innate immune genes.
FUNEVO bridges the fields of evolutionary biology and antiviral innate immunology to decipher conceptual novelties on the evolutionary rules governing mammalian immunity.
Aim 1 combines phylogenomics, with state-of-the-art CRISPR loss-of-function and homologs’ gain-of-function antiviral screens, in the Myotis cross-discipline model platform that we newly established, to discover immune innovations driving antiviral specificity. In Aim 2, we use recent breakthroughs in genomics and protein domain structure predictions to identify and quantify immune innovations during mammalian evolution. In Aim 3, through ancestral reconstructions combined with mechanistic characterization, we will understand how the identified gene duplications and domain rearrangements led to functional novelty.
Overall, our evolution-guided approach will unveil novel antiviral genes that emerged in mammals, shedding lights on the evolutionary principles that were crucial to innate immune evolution and have the potential to inspire future disease therapy.
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 genetics
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences evolutionary biology
- medical and health sciences basic medicine immunology
- natural sciences biological sciences zoology mammalogy
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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)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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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-ERC - HORIZON ERC Grants
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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) ERC-2025-COG
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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.
75794 PARIS
France
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