Objectif "Catabolism of amino acids is an ancient survival strategy that also controls immune responses in mammals. Indoleamine 2,3-dioxygenase (IDO), a tryptophan catabolizing enzyme, is recognized as an authentic regulator of immunity in several physiopathologic conditions, including autoimmune diseases, in which it is often defective, and neoplasia, in which it promotes immune unresponsiveness. The PI’s group recently revealed that IDO does not merely degrade tryptophan and produce immunoregulatory kynurenines but also acts as a signal-transducing molecule independently of its enzyme activity. IDO’s signaling function relies on the presence of phosphorylable motifs in a region (small IDO domain) distant from the catalytic site (large IDO domain). Preliminary data indicate that IDO, depending on microenvironmental conditions, can move among distinct cellular compartments. Thus IDO may be considered a ‘moonligthing’ protein, i.e. an ancestral metabolic molecule that, during evolution, has acquired the DYNAMIC feature of moving intracellularly and switching among distinct functions by changing its conformational state. By means of computational studies, Macchiarulo’s group (team member) has identified distinct conformations of IDO, some of which are associated with optimal catalytic activity of the enzyme whereas others may favor tyrosine phosphorylation of IDO’s small domain. A switch between distinct conformations can be induced by the use of ligands that bind either the catalytic site or an accessory pocket outside the IDO catalytic site. The first aim of DIDO is to decipher the relationships between IDO conformations and multiple functions of the enzyme. A second aim is to identify small molecules with drug-like properties capable of modulating distinct IDO’s molecular conformations in order to either potentiate (a new therapeutic approach in autoimmune diseases) or inhibit (more efficient anti-tumor therapeutic strategy) immunoregulatory signaling ability of IDO." Champ scientifique medical and health sciencesbasic medicineimmunologyautoimmune diseasesnatural sciencesbiological scienceszoologymammalogynatural scienceschemical sciencesorganic chemistryaminesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Programme(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) Thème(s) ERC-AG-LS7 - ERC Advanced Grant - Diagnostic tools, therapies and public health Appel à propositions ERC-2013-ADG Voir d’autres projets de cet appel Régime de financement ERC-AG - ERC Advanced Grant Institution d’accueil UNIVERSITA DEGLI STUDI DI PERUGIA Contribution de l’UE € 2 442 078,00 Adresse PIAZZA DELL UNIVERSITA 1 06123 Perugia Italie Voir sur la carte Région Centro (IT) Umbria Perugia Type d’activité Higher or Secondary Education Establishments Contact administratif Vincenzo Nicola Talesa (Prof.) Chercheur principal Ursula Grohmann (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire UNIVERSITA DEGLI STUDI DI PERUGIA Italie Contribution de l’UE € 2 442 078,00 Adresse PIAZZA DELL UNIVERSITA 1 06123 Perugia Voir sur la carte Région Centro (IT) Umbria Perugia Type d’activité Higher or Secondary Education Establishments Contact administratif Vincenzo Nicola Talesa (Prof.) Chercheur principal Ursula Grohmann (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
