INNATEDNASENSOR

A proteomic screen to identify cytoplasmic DNA sensor proteins mediating type I Interferon production

Coordinatore	CEMM - FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZIN GMBH    more  Organization address address: Dr. Ignaz Seipel-Platz 2 city: WIEN postcode: 1010 contact info Titolo: Ms. Nome: Sigrid Cognome: Strodl Email: send email Telefono: +43 1 4016070024 Fax: +43 1 40160970000
Nazionalità Coordinatore	Austria [AT]
Totale costo	180˙191 €
EC contributo	180˙191 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2011-IEF
Funding Scheme	MC-IEF
Anno di inizio	2013
Periodo (anno-mese-giorno)	2013-12-20   -   2015-12-19

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	CEMM - FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZIN GMBH  Organization address address: Dr. Ignaz Seipel-Platz 2 city: WIEN postcode: 1010 contact info Titolo: Ms. Nome: Sigrid Cognome: Strodl Email: send email Telefono: +43 1 4016070024 Fax: +43 1 40160970000	AT (WIEN)	coordinator	180˙191.40

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 Obiettivo del progetto (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.'