Objective
Detection of pathogens by the innate immune system depends on the recognition of microbial components by dedicated receptors. During viral and bacterial infections, pathogen-derived nucleic acids are recognized by innate receptors resulting in the production of type I IFNs and inflammatory cytokines. While it is established that cytoplasmic delivery of viral, bacterial and even host DNA triggers type I IFN production via a pathway depending on STING, TBK1, IKKe and IRF3, the identification of the upstream DNA-sensing molecule(s) remains a key issue to be elucidated. Some proteins (such as DAI and IFI16) have been proposed to play such a role, but available data indicate that additional receptor(s) must exist.
The primary goal of the proposed project is to identify new cytoplasmic DNA-sensing proteins mediating type I IFN induction. First, we will identify interferon inducible DNA-binding proteins by combining a systematic proteomics screen for proteins that associate with DNA with a screen for transcripts induced by interferon beta. Using bioinformatic analysis of these datasets, we will then select candidate proteins to perform functional investigation on. The effect of shRNA-mediated silencing or overexpression of these proteins on DNA-induced IFN production will be evaluated. Promising proteins will be selected for detailed characterization. Importantly, our project could also reveal proteins that do not participate in the sensing, but in the effector responses against pathogens, thereby opening other interesting research directions.
In addition to the relevance for antiviral and antibacterial immunity, a better understanding of DNA sensing pathways may have broader implications as for example DNA-induced IFN contributes to the immunogenicity of plasmid-based vaccines. Moreover, type I IFN induced by self-DNA has been linked to autoimmune diseases. Therefore, identification of new DNA sensing molecules will uncover new potential therapeutic targets.
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 proteomics
- natural sciences biological sciences biochemistry biomolecules nucleic acids
- natural sciences biological sciences genetics DNA
- medical and health sciences basic medicine immunology autoimmune diseases
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
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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.
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.
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-2011-IEF
See other projects for this call
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.
Coordinator
1090 Wien
Austria
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.