The general goal of this research is to understand how cells decide when, where and how to divide. Specifically, the regulation of cell division within the germline of the soil nematode, Caenorhabditis elegans, will be used as a paradigm to study this problem. Genetic, molecular and biochemical methods will be used to identify the genes that regulate the maturation of C. elegans oocytes. Oocyte maturation involves the precisely regulated progression of germline nuclei from pachynema to diakinesis during prophase I of the meiotic cell cycle. A major focus of this research will be to understand the function of the glv-1 gene, which is required for oocyte maturation. Intriguingly, glv-1 is also required for the control of somatic cell proliferation by the C. elegans homologue of the ras oncogene. The relationship between ras and glv-1 is of special interest, because the genes that function downstream of ras in the signal transduction pathway leading to cell division have not been clearly identified. These are potential targets for cancer therapy. The glv-1 gene will be cloned and sequenced to gain insight into its biochemical function. Reverse genetic experiments using the cloned glv-1 gene will allow specific hypotheses about gene function to be tested. Experiments will be performed to determine where and when glv-1 activity is required for the regulation of oocyte maturation. Genetic screens and selections will be employed to identify additional genes that act in the regulation of oocyte maturation. Studies will be initiated to determine the biochemical activities of these genes and to ascertain their functional relationships to glv-1. The study of C. elegans germline development in general, and oocyte maturation in particular, should provide valuable insights into the mechanisms that operate in multicellular organisms to permit tissue specific responses to general signalling pathways.
