The nematode Caenorhabditis elegans has recently emerged as a powerful model system for studying innate immunity. The short generation time of C. elegans, in combination with the abundance of well-defined genetic tools available for its study, makes it an ideal organism for the rapid dissection of innate immune response pathways. Previous studies have indicated that components of the C. elegans CED-3 programmed cell death pathway are required for defense of the worm against certain pathogens. The goal of the research described in this proposal is to elucidate the exact mechanism by which the CED-3 pathway provides protection. In particular, the aims are to: 1) Identify the location of defense-related CED-3-pathway activity within C. elegans, 2) Characterize the role of CED-3-regulated mucins in the defense response and 3) Define the genetic pathway leading from interaction with pathogen to expression of CED-3-regulated mucins. Importantly, because many innate immunity pathways appear to be highly conserved evolutionary, these studies could potentially provide insights not only into the C. elegans defense response, but also into unknown aspects of mammalian innate immunity. ? ? ?