Understanding the pathogenesis of polycystic kidney disease

Background: Polycystic kidney disease (PKD) is the most common potentially lethal Mendelian disease, affecting around 1/1000 people. It arises when cells of the kidney tubules over-proliferate, forming cysts which gradually expand and ablate normal kidney tissue. We have shown that the Aurora A Kinase is a central regulator of the development of cystic disease in a number of in vivo models of PKD. Project Aim/s: In this project we will examine a number of different mechanisms by which Aurka might be regulating the growth of renal cysts to better understand the how the protein functions, and to investigate it as a possible therapeutic target for treating the disease. Techniques: This project will examine mouse and cellular models of PKD and the biochemical functions of AURKA. It will utilise a broad range of techniques to do so including histology, immunohistochemistry and transcriptional profiling. Specific cell signalling pathways will be studied in vitro using tissue culture and various biochemical approaches to best understand gene and protein function.