The overall goal of the project is to study the role of primary cilia in renal cystic disease observed in three rare genetic disorders, namely OFDI, BBS and NPHP, associated with dysfunction of the primary cilium. To reach this goal the consortium is using and characterizing in vivo and in vitro systems that are already available and/or will be newly generated.

The specific objectives are as follows:

1. Generate in vivo models for these rare genetic conditions. These models will be utilized to establish a comprehensive list of phenotypic changes caused by abnormal BBS/OFD1/NPHP functions, delineating the commonalities between these three types of ciliopathies to predict the pathways involved in these diseases.

2. Determine the dynamics of BBS/OFD1/NPHP trafficking and recruitment to the cilium, providing a framework for the understanding of the pathophysiology of BBS/OFD1/NPHP mutations.

3. Determine the importance of BBS/OFD1/NPHP function for renal homeostasis, and address the role of BBS/OFD1/NPHP proteins in Wnt signalling and tubulogenesis.

4. Study the downstream pathway dysregulation events consequent upon the absence of BBS, OFD1 and NPHP proteins.

5. Identify, test and validate potential therapeutic agents for the amelioration and prevention of renal cyst – a major cause of morbidity and mortality in this group of patients and patients with related diseases.

Wednesday, May 13th, 2009 Aims, What is EUCILIA?