Skip to main content

Pathophysiology of rare diseases due to ciliary dysfunction: nephronophthisis, Oral-facial-digital type 1 and Bardet-Biedl syndromes

Objective

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.

Field of science

  • /medical and health sciences/basic medicine/physiology/pathophysiology
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /medical and health sciences/clinical medicine/nephrology
  • /medical and health sciences/basic medicine/physiology

Call for proposal

FP7-HEALTH-2007-A
See other projects for this call

Funding Scheme

CP-FP - Small or medium-scale focused research project

Coordinator

FONDAZIONE TELETHON
Address
Via Varese 16/B
00185 Roma
Italy
Activity type
Research Organisations
EU contribution
€ 1 110 637,08
Administrative Contact
Irene Mearelli (Ms.)

Participants (3)

University College London
United Kingdom
EU contribution
€ 700 090
Address
Gower Street
WC1E 6BT London
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Kent Lee (Mr.)
UNIVERSITAETSKLINIKUM FREIBURG
Germany
EU contribution
€ 838 500
Address
Hugstetter Strasse 49
79106 Freiburg
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Gerhard Henninger (Mr.)
FONDAZIONE MARIO NEGRI SUD-CENTRO DI RICERCHE FARMACOLOGICHE EB IOMEDICHE

Participation ended

Italy
EU contribution
€ 281 072,92
Address
Via Nazionale 8A
66030 Santa Maria Imbaro
Activity type
Research Organisations
Administrative Contact
Claude Alain Di Menno Di Bucchianico (Mr.)