Obiettivo Type I interferons represent both key molecules in anti-viral defence and mediators of inflammatory disease, so that the induction, transmission and resolution of the interferon response are tightly regulated - balancing protection against infection versus the risk of immunopathology. Monogenic type I interferonopathies (T1IFNs), and related ‘complex’ phenotypes such as systemic lupus erythematosus and dermatomyositis, represent examples of a disturbance of the homeostatic control of this system, where a constitutive upregulation of type I interferon activity is considered directly relevant to pathology. Set against the absence of a routine assay in clinical medicine for the detection of upregulated type I interferon, the current application addresses major questions in the developing T1IFN field. Analogous to other screening strategies (e.g. using mouse ENU mutagenesis or yeast gene deletion series), we have established a pipeline for the systematic identification of human mutant states predisposing to upregulated type I interferon signalling. Such an approach will allow for the comprehensive definition of important themes in interferon biology, informing our understanding of anti-viral signalling and self-non-self discrimination. Furthermore, these studies will have direct translational benefit - since the identification of a phenotype as a T1IFN implies the possibility of therapy to reduce type I interferon levels and / or block interferon signalling. Campo scientifico medical and health scienceshealth sciencesinflammatory diseasessocial sciencessociologysocial issuessocial inequalitiesmedical and health sciencesbasic medicinepathologymedical and health sciencesclinical medicinemedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantivirals Parole chiave Type I interferon type I interferonopathies innate immunity Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-2017-ADG - ERC Advanced Grant Invito a presentare proposte ERC-2017-ADG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-ADG - Advanced Grant Istituzione ospitante THE UNIVERSITY OF EDINBURGH Contribution nette de l'UE € 2 156 300,00 Indirizzo OLD COLLEGE, SOUTH BRIDGE EH8 9YL Edinburgh Regno Unito Mostra sulla mappa Regione Scotland Eastern Scotland Edinburgh Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 2 156 300,00 Beneficiari (2) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto THE UNIVERSITY OF EDINBURGH Regno Unito Contribution nette de l'UE € 2 156 300,00 Indirizzo OLD COLLEGE, SOUTH BRIDGE EH8 9YL Edinburgh Mostra sulla mappa Regione Scotland Eastern Scotland Edinburgh Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 2 156 300,00 IMAGINE INSTITUT DES MALADIES GENETIQUES NECKER ENFANTS MALADES FONDATION Francia Contribution nette de l'UE € 262 500,00 Indirizzo 24 BD DU MONTPARNASSE 75015 Paris Mostra sulla mappa Regione Ile-de-France Ile-de-France Paris Tipo di attività Research Organisations Collegamenti Contatta l’organizzazione Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 262 500,00