| Normal cells develop into cancer cells in a multistep process by acquiring mutations and chromosomal aberrations. Ultimately the cancer cell will have the capacity for unlimited proliferation, independent of its cellular environment. However, oncogenes may display increased dependence on normal cellular processes and normal genes. Developing cancer cells may become non-oncogene addicted. Genes that are dependent on each other in such a way are said to interact. The model system that is most accessible to study genetic interactions is yeast. We propose to search for genes, in a genome wide manner, that interact with oncogenes. We will make yeast strains that over-express the yeast orthologues of a specific oncogene or genes over-expressed specifically in cancer cells. In an automated manner, in these strains, each gene will individually be deleted. We will look for gene deletions that will give a growth defect in the oncogene overexpressing strain and not in the wt strain. Novel genes will be validated in cancer cell lines using shRNA. The genes discovered by the screen will, by definition, be potential therapeutic targets. Additionally, the yeast model system will be exploited to further investigate novel interacting genes. |
