C-myc is a protooncogene, whose deregulated expression leads to inducti of proliferation and apoptosis. Myc-induced apoptosis is mediated by Myc/Max heterodimers and clearly depends on it ability to activate transcription. However, the underlying molecular and biochemical mechanisms are so far poorly understood. In C. elegans genetic studies have identified a genetic pathway for apoptosis. For this pathway the genes ced-3, ced-4 and ced-9 are important. Various data support the idea that the pathways regulating apoptosis in C. elegans and mammals are highly conserved. therefore it is likely that apoptosis will be controlled in cell type-specific fashion, but that the basic elements of the death machinery might be universal. Ced-3 is homolog to the ICE protease whereas ced-9 shows homolgy to the human bc1-2 gene. Both genes seem to be involved in different forms of mammalian cell death. For Bc1-2 it has been demonstrated that it blocks Myc-induced apoptosis. In contrast l to this the role of ICE proteases in Myc-induced apoptosis is not clear. The aim of the proposed experiments is therefore to gain g sights into the role of ICE and ICE-like protease in the process of Myc-induced apoptosis. Training content (objective, benefit and expected impact) With th post-doctorial training I would like to become more qualified for a scientific career. I am expecting to work independently on my own project but in close contact with other scientists. The lab of Dr. Gerad Evan is well-known for their work in the field of apoptosis. During my Ph.D. I became familiar with certain aspects of the Myc oncogene and with this post doc I would like to investigate other aspects of this oncogene namely i role in apoptosis. The ICRF, London is a very famous and well established institute. The facilities availabe offer a lot of experimental opportunities.The daily seminars given at the institute will promote scientific exchange. So it will be easy to profit from scientific experience at the technical and intelectual level. After this post-doc I will be able to tranfer a lot of this knowledge back to a german resear institute. Links with industry / industrial relevance (22) The pro apoptosis is an important mechanism to prevent tumor formation. Understanding the underlying basic mechanisms of apoptosis will be important for progress in cancer therapy. ?