Investigation of molecular interplay between Nphp2- and Bbs4 and its role in ciliogenesis, cilia maintenance and developmental signalling pathways

• Applicant: Dr. Miriam Schmidts
• Subject Area: Pediatric and Adolescent Medicine
• Term: from 2009 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 124067310

Cilia are highly conserved cell organelles present on most eukaryotic cells. Numerous multisystem disorders due to mutation in genes encoding for ciliary proteins are known. Among them are Bardet-Biedl-syndrome (BBS), and Nephronopthisis. Interestingly, BBS and Nephronopthisis share an overlapping phenotype despite the fact that they are caused by completely different mutated genes, indicating that these ciliary proteins might act synergistically or additive in similar pathways. Therefore, this human disease orientated basic research project will aim to identify the molecular interplay of the ciliary Bbs- and nephronophtisis protein complex and try to elucidate their interaction in development and maintenance of the cilium. Potentially involved cell signalling pathways such as Shh and Wnt signalling will be examined using bigenic animal models (compound heterozygous and double knockout Bbs4-Nphp2 (Inversin)-mice and zebrafish). Complementary protein functions on developmental signalling pathways will be assessed by in vitro experiments such as gene knockdown. The combined input of genetic and mechanistic studies, derived from multiple animal models, should provide a better understanding of BBS and other complex ciliary diseases. This understanding will be essential to develop targeted medical therapies in ciliary diseases.

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Professor Dr. Philip L. Beales