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A possible new role of type I interferon (IFN)-mediated survival of influenza A virus (IAV)-infected lung cells in lung repair

Project description

Viral survivors: the architects of lung recovery

Severe influenza infections cause lasting lung damage and pose a major global health threat. While the immune system usually clears infected cells, some vital lung progenitor cells – the building blocks of repair – survive the virus. Supported by the Marie Skłodowska-Curie Actions programme, the RIPAIR project will investigate how these ‘survivor cells’ contribute to lung regeneration. Using cutting-edge mouse models, human lung organoids and RNA sequencing, RIPAIR will map these cells to determine how they drive tissue recovery. The project will also provide advanced training for researchers and foster international collaboration. Ultimately, the project aims to identify new targets to support lung recovery, helping prevent long-term respiratory failure that occurs when natural repair processes fail.

Objective

Lower respiratory tract infections caused by influenza viruses remain a leading cause of morbidity and mortality worldwide and predispose individuals to secondary respiratory disease. Type I interferon (IFN) protects against severe disease by blocking or restricting viral replication before the immune system clears those infected cells. However, a new concept has emerged from studies done in mice, suggesting that a significant proportion of lung progenitor cells survive influenza A virus (IAV) infection in an IFN-dependent manner without clearance. The RIPAIR project will investigate the relevance and function of these IAV-survivor cells in lung repair, by studying if (i) a specific innate immune response in progenitor cells mediates their preferential resistance to IAV, (ii) these surviving progenitor cells enhance the lung's ability to regenerate, and (iii) these survivor progenitor cells are also present in human lung tissue after IAV infection, where they contribute to tissue repair. Understanding these mechanisms is critical as failing repair might negatively impact cell survival (“RIP air”).
This project combines the expertise of an aspiring young researcher trained in viral immunopathogenesis with that of an experienced host specialized in IAV biology and long-term RNA virus consequences. Using state-of-the-art mouse and human lung organoid systems, genetically engineered in vivo models, and unbiased RNA sequencing, RIPAIR will visualize and functionally characterize survivor progenitor cells to uncover if and how they contribute to tissue recovery, both in an animal and human model. In the long term, this basic research project may inspire new directions for identifying targets that support lung recovery after IAV infection. Simultaneously, RIPAIR will provide advanced training in cutting-edge methodologies, foster interdisciplinary collaboration, and strengthen the fellow’s career development within an international and stimulating research environment.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

UNIVERSITAETSKLINIKUM FREIBURG
Net EU contribution

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.

€ 217 965,12
Address
HUGSTETTER STRASSE 49
79106 Freiburg
Germany

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Region
Baden-Württemberg Freiburg Freiburg im Breisgau, Stadtkreis
Activity type
Higher or Secondary Education Establishments
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Total cost

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