Project description DEENESFRITPL The road from inflammation to cancer Inflammation involves the activation and recruitment of cells and factors from the adaptive and innate immune systems at a site of infection or damage. Initially recognised as a key defence process against pathogens, inflammation is now known to contribute to cancer formation. Understanding the molecular determinants of inflammatory pathways in cancer will help develop more effective therapies. Funded by the European Research Council, the CrlC project will focus on the SLX4 DNA damage repair complex, which is mutated in Fanconi Anemia (FA), a syndrome characterised by increased cancer susceptibility and a defective immune system. The working hypothesis is that chronic inflammation emerges because pathological nucleic acids are recognised by the immune system. Show the project objective Hide the project objective Objective Cancer related inflammation (CRI) is a well-established hallmark of cancer. We recently demonstrated that the DNA damage repair SLX4 complex suppresses spontaneous and human immunodeficiency virus (HIV)-dependent pro-inflammatory cytokine production, revealing a role for this DNA repair complex in controlling innate immune responses. Bi-allelic mutations in SLX4 are involved in the onset of Fanconi Anemia (FA), a syndrome characterized, besides heightened cancer susceptibility, by severe defects of the immune system, resulting from increased pro-inflammatory cytokine levels and progressive bone marrow failure. Within this proposal, using SLX4-deficiency as a working model, I aim at investigating the molecular process underlying CRI. Based on our previous observation that the SLX4 complex binds to HIV-derived reverse-transcripts and promotes their degradation, my working hypothesis is that CRI results from the accumulation of endogenous pathological nucleic acids that are recognized by the innate immune system in the absence of SLX4. The present project should unveil the relationship between repression of pro-inflammatory cytokine production by proteins involved in DNA repair, DNA damage, and CRI, thereby opening unforeseen perspectives in the treatment of cancer patients. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acidsnatural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicineimmunologymedical and health sciencesclinical medicineoncology Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-StG-2014 - ERC Starting Grant Call for proposal ERC-2014-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Coordinator CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS Net EU contribution € 1 500 000,00 Address Rue michel ange 3 75794 Paris France See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS France Net EU contribution € 1 500 000,00 Address Rue michel ange 3 75794 Paris See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
