Programmed cell death (PCD) is a virtual ubiquitous component of eukaryotic development and its aberrant regulation contributes to several pathological conditions. This proposal seeks to investigate the molecular control of PCD in the nematode Caenorhabditis elegans. Two broad areas of research are described. First the C. elegans homologue of the vertebrate dad-1 gene will be studied. Knockout mutations in Ce-dad-1 will be found, dad-1 RNA and protein products will be localized, and interaction with other cell death genes will be investigated. Second, additional genes that either are needed for PCD or prevent its occurrence will be identified by examining the mutant phenotypes of embryos that are homozygous for deletions within the C. elegans genome. The cloning and characterization of the genes causing the PCD defects will then be carried out.
Sugimoto, A; Kusano, A; Hozak, R R et al. (2001) Many genomic regions are required for normal embryonic programmed cell death in Caenorhabditis elegans. Genetics 158:237-52 |
Derry, W B; Putzke, A P; Rothman, J H (2001) Caenorhabditis elegans p53: role in apoptosis, meiosis, and stress resistance. Science 294:591-5 |
Ferguson, K C; Rothman, J H (1999) Alterations in the conserved SL1 trans-spliced leader of Caenorhabditis elegans demonstrate flexibility in length and sequence requirements in vivo. Mol Cell Biol 19:1892-900 |