Objective
Influenza infections kill around 300.000 people each year. Due to its ability to reassort with viruses from other animal species and its mutational drift, society is in great need of novel vaccination strategies. Autophagy is involved in the delivery and processing of antigens derived from different viruses. Influenza and other viruses often target this important mechanism to evade immune recognition.
Here, I aim at unraveling the molecular mechanisms underlying the fusion of autophagosomes with antigen loading compartments, the late endosomal MHC class II containing compartment and the putative endosomal MHC class I loading compartment, which comes into play when the regular MHC class I route is blocked by viruses. To this end, I will apply RNAinterference screening combined with immune fluorescence microscopy. To further elucidate the cross-talk between viral proteins and the autophagy machinery I will investigate matrix protein 2 (M2) of Influenza A. M2 was shown to cause a block of autophagosome/lysosome fusion, which in turn leads to an accumulation of viral antigens in autophagosomes. I will identify the cellular players interacting with M2 and the mechanism of regulation. Furthermore, the role of autophagy in antigen presentation after Influenza A infection will be addressed applying an inducible mouse model of autophagy deficiency in alveolar type II cells, the main target of Influenza A infection in mice.
By integrating all findings (molecular mechanism of antigen delivery at steady-state and in viral infection, manipulation of the host machinery by M2, role of autophagy in viral immunogenicity) I will gain a broad overview of the regulation of autophagosome fusion in health and disease. This will help the field to advance in finding new ways to target Influenza infections. However, the implication of these findings is not necessarily limited to infection, as autophagy also plays a major role in many other diseases, such as neurodegenerative diseases.
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
- medical and health sciences health sciences infectious diseases viral diseases RNA viruses influenza
- natural sciences physical sciences optics microscopy
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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.
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.
FP7-PEOPLE-2013-IEF
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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.
Coordinator
Zürich
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