Workpackage 4 - Aire Genomics and Biology
Last updated 2006-10-17
APS I and Aire molecule provide an excellent biological model to create increased understanding of the molecular details of autoimmunity. Although presenting a gene defective in a monogenic autoimmune disease, it will most probably guide us to new signalling pathways resulting in an abnormal, tissue and cell-specific processes of autoimmunity. In this WP we will collect detailed understanding of the regulatory elements of Aire as well as that of the target genes regulated by Aire. We will use mouse models and cellular models and analyze them using genome-wide expression assays, targeted analyses of protein-protein interactions and well-designed crossings of Aire KO mice with established mouse strains to address the partners of the Aire-containing transcriptional complex. The collected information will contribute to the increased understanding of the molecular events of autoimmunity generally and pave the way towards targeted interventions aiming to early intervention in the pathogenesis.
We will identify genes and gene products, specifically autoantigens, regulated by Aire, as well as key regulators of the cell-and tissue specific expression of the Aire gene.
We will produce comprehensive database containing the expression profiles of cells and tissues defective of Aire in KO mouse and, for available tissues, also for APS I patients making data available to others studying molecular pathogenesis of autoimmune diseases.
We will identify proteins involved in the molecular complexes with Aire and essential for the normal functions of this autoimmune regulator.