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Role of Polycystic Kidney disease proteins in establishing and maintaining tubular structure


Autosomal Dominant Polycystic Kidney Disease (ADPKD) is one of the most common genetic diseases, affecting more than 12 million people worldwide. Two genes have been linked to the disease, PKD1, responsible for 85% of cases, and PKD2 for 15%.

The genes are developmentally regulated and believed to play a key role in renal tubular differentiation. So little is known about the molecular aspects of the disease, including the function of the two gene products Polycystin-1 (PC-1) and 2 (PC-2), that no remedies have been identified to date. PKD causes 10% of all the renal transplantations in the world and in Europe.

Only recently the function of the two proteins started to be unravelled. PC-1 is a 520kDa non-tyrosine kinase receptor involved in cell-cell/matrix interactions and in primary cilia function. PC-2 is a calcium channel most likely at the plasma membrane and in primary cilia. This Marie Curie Excellence Grant proposal seeks support for the implementation of a newly developed group based in Italy upon return of its team leader from the USA.

The team leader was the first one to succeed in expression of full-length PC-1 and to generate a functional model for the protein. She now proposes to assemble an international excellence group to continue molecular studies on ADPKD using the invaluable tools generated as well as developing novel ones.

The broad projects proposed include:
- identification of a ligand for PC-1;
- characterization of a polyproline sequence in the C-terminus of PC-1 and determination of its functional role within the context of the full-length molecule;
- in vivo studies on the role of PC-1 in renal development and generation of animal models to better understand the disease.

The team is part of the prestigious Dulbecco Telethon Institute (D TI), a virtual Institute created to counteract brain drain and will be located in the foremost Institute for Molecular Medicine in Italy, Dibit-San Raffaele Hospital.

Call for proposal

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Via Guglielmo Saliceto, 5