Project 172610

Accumulation of hazardous mutations is responsible for cancer development. Many genes prone to mutation in cancer are evolutionarily conserved, and their homologs have been identified in different species. Rb was the first identified tumor suppressor gene whose mutations were found in a childhood cancer, Retinoblastoma. Most cancer cells possess inactive Rb, which is targeted by various oncogenic events. Therefore, if one can find genes that can control the survival and/or proliferation of Rb deficient cells, they can be potentially used to specifically target cancer cells. The homolog of Rb, rbf1, was identified in the fruit fly, Drosophila melanogaster, and its biological activity is found to be well-conserved. Recent advance in genetic tools and techniques has made Drosophila an attractive model organism to study human cancer genes. Using Drosophila, I propose to investigate genes that can cooperate with the loss-of-Rb to promote cell death. I have recently discovered that another tumour suppressor gene, tsc1, cooperates with rbf1 to regulate cell death, and conducted a genetic screen to identify novel genes that can specifically promote cell death in rbf1 mutant cells. In this proposal, I describe experimental plans to further characterize these findings.