Wilms tumour is a kidney cancer that is quite common in children during the first 5 years of life. It is clearly a remarkable example of cancer arising through the normal processes of development going wrong. In order to understand how the tumour develops with a view to better treatments, we have to understand the processes of normal kidney development and how these go awry on the route to tumorigenesis. We are studying a Wilms tumour predisposition gene, WT1, mutations in which result in Wilms tumour but may also lead to other life-threatening kidney diseases and abnormalities of the sexual organs. We have shown that this gene is vital for normal kidney, testis and ovary development and one of our major goals is to understand how WT1 controls differentiation of these tissues and why disease develops when the gene is mutated. We have shown that WT1 is necessary for cells to divide and to prevent differentiation in certain tissues such as blood vessels of the heart. We propose to dissect WT1s role in these processes and to test the idea that it may play a major role in stem cell maintenance, tissue repair and in adult cancer. We have also shown WT1 is a remarkable example of a single gene encoding multiple proteins that may differentially regulate gene expression both in the nucleus and in the cytoplasm. One of our major goals is to understand these functions and how they control normal development and disease. We are taking a multidisciplinary approach to our work and are trying to set-up novel systems in culture to test the function of WT1 and associated genes.