Project 170995

Cells that make up the tissues and organs of multicellular organisms must be maintained at a relatively constant number to maintain viability and prevent disease. If this intricate balancing act is tipped to favour too much cell survival an organism can develop cancerous tumors. Genes that regulate cell survival and suppress cancer are well conserved in evolution and are easy to study in simple organisms, such as worms and flies. We use the nematode worm Caenorhabditis elegans as a model system to understand the molecular basis of how these genes regulate cell death. In the previous granting period we discovered a novel gene that controls the killing activity of tumor suppressor p53, the most frequently mutated gene in human cancer. Recently, we translated this discovery to human cancer cells and found that the human equivalent of this gene (FBX045) possesses similar cell killing properties as the worm gene. We propose here to determine the mechanism by which this gene controls the cell killing activity of p53 using a combination of genetics and molecular approaches in C. elegans and human tumor cells. We anticipate that these studies will lay the foundations for designing new and more effective therapeutics for the clinical treatment of cancer.

using C. elegans as a model system to study the p53 tumor suppressor pathway and its regulation by a novel gene (FBXO45)