The prion diseases are a group of neurodegenerative disorders occurring in both humans and animals. These diseases are caused by a unique "infectious" pathogen which seems to be composed only of an abnormal isoform of a host encoded protein denoted PrPsc. The normal prion protein (PrP) designated PrPc is anchored to the surface of cells by a glycoinositol phospholipid but its function remains unknown. The human prion diseases are manifest as infectious, genetic and sporadic illnesses. For many years, the prion diseases were classified as slow virus infections and they were resistant to investigation. The discovery of the PrPsc followed by molecular cloning of the PrP gene opened many new avenues of investigation. Recently, transgenic (Tg) mice expressing foreign and mutant PrP genes have been constructed as well as mice devoid of PrP (Pm-p%). Purification of PrPc and PrPsc have permitted studies showing profound differences in the conformation of these two isoforms. We propose to exploit some of these recent advances in studies of prions to elucidate the mechanism of PrPsc formation, the function of PrPc and the diversity of prions as manifest by "strains" producing different patterns of disease. Computer graphics are required to carry out protein sequence analysis and comparison, to display protein structures and to manipulate then in order to produce a model capable of rationalizing experimental data and to guide future experiments. In addition, we are investigating the sequences of six newly-identified prion-binding proteins, to try to determine any features or functionalities they have in common.