The main goal of our grant application is to identify novel genes that function in apoptosis (programmed cell death), using the C. elegans cell death suppressor CED-9 as our starting point for an extensive yeast two-hybrid screen. In the first year of funding, we have concentrated our attention on our discovery of a specific interaction between CED-9 and CED-4, one of the proapoptotic proteins in C. elegans. We showed that CED-4 is likely to be a major target for CED-9 action. We have also initiated work on Apaf-l, the mammalian homolog of CED-4. We have developed a simple model for how the apoptotic machinery is regulated in C. elegans. This model is now being tested, both in worms and in mammals. In the coming years, we plan to concentrate our attention back on the several other CED-9- interacting clones that we isolated in our screen.