Necrosis is more than a phenomenon of uncontrolled cell death. There is increasing evidence to suggest that necrosis is genetically programmed. We are exploiting a new model to investigate necrotic cell death. In worms that lack
pnc-1 nicotinamidase, the four
uv1 cells die by necrosis (1). We want to investigate why
uv1 cells die in
pnc-1 mutants and to identify genes that promote or inhibit
uv1 cell necrosis. In
pnc-1 mutant animals with a
uv1 cell specific GFP transgene, we can screen for rescue of
uv1 cell necrosis by screening for animals that retain the
uv1 GFP signal. We aim to screen using the genome-wide RNAi library and expect to gain insight into how and why
uv1 cells die in
pnc-1 mutants. We are using a split GFP system to engineer animals with
uv1 cell specific GFP expression for this screen (2), and we will discuss progress in engineering the strain and preparing for the screen. Reference: 1. EGF signaling overcomes a uterine cell death associated with temporal mis-coordination of organogenesis within the C. elegans egg-laying apparatus. Li Huang , Hanna-Rose Wendy 2. Antiparallel Leucine Zipper-Directed Protein Reassembly: Application to the Green Fluorescent Protein. Indraneel Ghosh , Andrew D. Hamilton , Lynne Regan.