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.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Genetics Study Section (GEN)
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Dartmouth College
Schools of Arts and Sciences
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Lambie, Eric J; Bruce 3rd, Robert D; Zielich, Jeffrey et al. (2015) Novel Alleles of gon-2, a C. elegans Ortholog of Mammalian TRPM6 and TRPM7, Obtained by Genetic Reversion Screens. PLoS One 10:e0143445
Lee, Min-Ho; Ohmachi, Mitsue; Arur, Swathi et al. (2007) Multiple functions and dynamic activation of MPK-1 extracellular signal-regulated kinase signaling in Caenorhabditis elegans germline development. Genetics 177:2039-62
Kemp, Benedict J; Hatzold, Julia; Sternick, Laura A et al. (2007) In vivo construction of recombinant molecules within the Caenorhabditis elegans germ line using short regions of terminal homology. Nucleic Acids Res 35:e133
Chen, Carlos Chih-Hsiung; Schweinsberg, Peter J; Vashist, Shilpa et al. (2006) RAB-10 is required for endocytic recycling in the Caenorhabditis elegans intestine. Mol Biol Cell 17:1286-97
Teramoto, Takayuki; Lambie, Eric J; Iwasaki, Kouichi (2005) Differential regulation of TRPM channels governs electrolyte homeostasis in the C. elegans intestine. Cell Metab 1:343-54
Church, Diane L; Lambie, Eric J (2003) The promotion of gonadal cell divisions by the Caenorhabditis elegans TRPM cation channel GON-2 is antagonized by GEM-4 copine. Genetics 165:563-74
Lambie, Eric J (2002) Cell proliferation and growth in C. elegans. Bioessays 24:38-53
West, R J; Sun, A Y; Church, D L et al. (2001) The C. elegans gon-2 gene encodes a putative TRP cation channel protein required for mitotic cell cycle progression. Gene 266:103-10
Sun, A Y; Lambie, E J (1997) gon-2, a gene required for gonadogenesis in Caenorhabditis elegans. Genetics 147:1077-89
Church, D L; Guan, K L; Lambie, E J (1995) Three genes of the MAP kinase cascade, mek-2, mpk-1/sur-1 and let-60 ras, are required for meiotic cell cycle progression in Caenorhabditis elegans. Development 121:2525-35