Objectif Primary cilia have been recognized on nearly all-mammalian cells. Emerging data suggest that they act as cellular antennae with diverse motility and sensory functions, detecting a wide variety of signals. As such, defects in cilia formation or function have profound effects on the development of body pattern and the physiology of multiple organ systems. Ciliary defects underlie a wide range of human disorders, including the rare and heritable Bardet-Biedl (BBS), Oro-facial-digital type 1 (OFD1) and nephronophthisis (NPHP) syndromes. Each of these disorders present with defining features but all are characterized by polycystic renal disease. The proteins encoded by the genes responsible for these disorders, as well as those implicated in heritable forms of cystic kidneys, are all located to the cilium/basal body/centrosome complex, suggesting that ciliary dysfunction might be the unifying pathogenic concept underlying cystic kidney disease. However, the molecular mechanisms remain undetermined. We propose to use BBS, OFD1 and NPHP syndromes as model systems to study the physiological role of primary cilia, with special emphasis on their role in the genitourinary tract and in the development of renal cysts. The experimental plan proposes to generate and make available to the scientific community in vitro and in vivo models to study the physiological role of primary cilia and of OFD1, BBS and NPHP proteins in the formation and function of the primary cilium. These tools will allow the analysis of the ciliary protein interaction network and of the downstream pathway in the absence of BBS, OFD1, or NPHP. Finally, we propose to identify and evaluate potential therapeutic agents. The biological relevance and significance of the results obtained will have implications far beyond the rare OFD1, BBS and NPHP patients and may shed light on the mechanisms underlying the role of primary cilia in polycystic kidney disease paving the way to possible new therapeutic approaches. Champ scientifique medical and health sciencesbasic medicinephysiologypathophysiologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicinenephrologykidney diseases Mots‑clés animal models cilia polycystic kidney rare diseases Programme(s) FP7-HEALTH - Specific Programme "Cooperation": Health Thème(s) HEALTH-2007-2.4.4-1 - Natural course and pathophysiology of rare diseases Appel à propositions FP7-HEALTH-2007-A Voir d’autres projets de cet appel Régime de financement CP-FP - Small or medium-scale focused research project Coordinateur FONDAZIONE TELETHON ETS Contribution de l’UE € 1 110 637,08 Adresse VIA VARESE 16/B 00185 Roma Italie Voir sur la carte Région Centro (IT) Lazio Roma Type d’activité Research Organisations Contact administratif Irene Mearelli (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Participants (3) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire UNIVERSITY COLLEGE LONDON Contribution de l’UE € 700 090,00 Adresse GOWER STREET WC1E 6BT LONDON Voir sur la carte Type d’activité Higher or Secondary Education Establishments Contact administratif Kent Lee (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée UNIVERSITAETSKLINIKUM FREIBURG Allemagne Contribution de l’UE € 838 500,00 Adresse HUGSTETTER STRASSE 49 79106 Freiburg Voir sur la carte Région Baden-Württemberg Freiburg Freiburg im Breisgau, Stadtkreis Type d’activité Higher or Secondary Education Establishments Contact administratif Gerhard Henninger (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée CONSORZIO MARIO NEGRI SUD. Participation terminée Italie Contribution de l’UE € 281 072,92 Adresse Via Nazionale 8/A 66030 SANTA MARIA IMBARO Voir sur la carte Type d’activité Research Organisations Contact administratif Claude Alain Di Menno Di Bucchianico (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée