Cel 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. Dziedzina nauki medical and health sciencesbasic medicinephysiologypathophysiologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicinenephrologykidney diseases Słowa kluczowe animal models cilia polycystic kidney rare diseases Program(-y) FP7-HEALTH - Specific Programme "Cooperation": Health Temat(-y) HEALTH-2007-2.4.4-1 - Natural course and pathophysiology of rare diseases Zaproszenie do składania wniosków FP7-HEALTH-2007-A Zobacz inne projekty w ramach tego zaproszenia System finansowania CP-FP - Small or medium-scale focused research project Koordynator FONDAZIONE TELETHON ETS Wkład UE € 1 110 637,08 Adres VIA VARESE 16/B 00185 Roma Włochy Zobacz na mapie Region Centro (IT) Lazio Roma Rodzaj działalności Research Organisations Kontakt administracyjny Irene Mearelli (Ms.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych Uczestnicy (3) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko UNIVERSITY COLLEGE LONDON Wkład UE € 700 090,00 Adres GOWER STREET WC1E 6BT LONDON Zobacz na mapie Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Kent Lee (Mr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych UNIVERSITAETSKLINIKUM FREIBURG Niemcy Wkład UE € 838 500,00 Adres HUGSTETTER STRASSE 49 79106 Freiburg Zobacz na mapie Region Baden-Württemberg Freiburg Freiburg im Breisgau, Stadtkreis Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Gerhard Henninger (Mr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych CONSORZIO MARIO NEGRI SUD. Zakończenie uczestnictwa Włochy Wkład UE € 281 072,92 Adres Via Nazionale 8/A 66030 SANTA MARIA IMBARO Zobacz na mapie Rodzaj działalności Research Organisations Kontakt administracyjny Claude Alain Di Menno Di Bucchianico (Mr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych