Objetivo Although the concept of grouping Mendelian disorders associated with an up-regulation of type I interferon (IFN) has not been previously recognised in the medical literature, my past and current work argues that this concept has scientific validity and clinical utility. I believe that such conditions, which include Aicardi-Goutières syndrome (AGS), spondyloenchondrodysplasia, and some cases of systemic lupus erythematosus (SLE), can usefully be considered to represent a novel set of inborn errors of immunity, and that the recognition of diseases as type I interferonopathies will have significance for the development of targeted therapies, as well as informing our understanding of viral and retroelement biology, and the pathogenesis of some forms of autoimmunity.This proposal will combine my expert phenotyping skills with revolutionary sequencing technologies, cutting edge systems for the interrogation of retroelements, and contemporary immunological assays. Deliberately focusing on human studies, I will identify new disease-related genes for AGS and lupus, and define currently unrecognised phenotypes arising from a dysregulation of type I IFN metabolism. I hypothesise that, to a currently undefined extent, SLE represents a heterogeneous collection of individually rare Mendelian subtypes, and suggest that the definition of new genetic subtypes of lupus will deliver a step change in our knowledge of disease pathogenesis through the delineation of pathways relevant to larger groups of patients. Since gene identification frequently represents a first step in understanding relevant cell biology, the work described herein has the potential to transform the clinical management of type I interferonopathies through the development of directed therapeutic approaches. Furthermore, I believe that our proposed experiments to study retroelement biology in the AGS-context are likely to reveal truly exciting insights into the activity and control of ‘junk’ DNA. Ámbito científico natural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencescell biology Programa(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Tema(s) ERC-SG-LS2 - ERC Starting Grant - Genetics,Genomics,Bioinformatics and Systems Biology Convocatoria de propuestas ERC-2012-StG_20111109 Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-SG - ERC Starting Grant Institución de acogida THE UNIVERSITY OF EDINBURGH Aportación de la UE € 181 585,11 Dirección OLD COLLEGE, SOUTH BRIDGE EH8 9YL Edinburgh Reino Unido Ver en el mapa Región Scotland Eastern Scotland Edinburgh Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Alan Kennedy (Mr.) Investigador principal Yanick Crow (Prof.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (3) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo THE UNIVERSITY OF EDINBURGH Reino Unido Aportación de la UE € 181 585,11 Dirección OLD COLLEGE, SOUTH BRIDGE EH8 9YL Edinburgh Ver en el mapa Región Scotland Eastern Scotland Edinburgh Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Alan Kennedy (Mr.) Investigador principal Yanick Crow (Prof.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE La participación finalizó Francia Aportación de la UE € 745 857,75 Dirección RUE DE TOLBIAC 101 75654 Paris Ver en el mapa Región Ile-de-France Ile-de-France Paris Tipo de actividad Research Organisations Contacto administrativo Marie-Pierre Sarrazin (Ms.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos THE UNIVERSITY OF MANCHESTER La participación finalizó Reino Unido Aportación de la UE € 571 463,14 Dirección OXFORD ROAD M13 9PL Manchester Ver en el mapa Región North West (England) Greater Manchester Manchester Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Claire Faichnie (Ms.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos
