Dr. Sedivy has developed a gene targeting method for mammalian cells in culture. Using this method he will first develop null mutants of the cellular proto-oncogenes c-myc, c-raf, and rb. He will avoid the possibility of lethality by providing an extra but conditional copy of these genes. The main purpose is to determine the normal function of these genes. Since aberrant expression of these genes have been implicated in cancerous cells, an understanding of their functions in normal cells may provide information useful to our understanding of the cancer transformation process.