To provide information on the metabolism of glycosphingolipids in vivo, using cultured skin fibroblasts from normal donors and donors with the neurological lipid-storage disorders, Gaucher's and Tay-Sachs Diseases with emphasis upon isolation from these cells, purification, and characterization of the deficient hydrolases, regulatory proteins, and activating co-factors, using chromatographic and immunologic techniques. This information should lead to steps aimed at a logical control of these destructive diseases. To investigate the role of beta-galactoside-specific lectin and complex glycosphingolipids in the mechanism of chick embryo myoblast fusion in culture, and the effects of competitive oligosaccharides, lectins, and pathogenic proteins, utilizing techniques for specific labelling of glycosphingolipids in vivo and affinity chromatographic and immunological approach to lectin identification, so as to arrive at an approach toward the correction of the defects in muscular dystrophies and multiple sclerosis. To investigate the role of synaptic sialidase-sialoprotein-sialolipid complexes in neurotransmitter binding and release by specifically labelling, isolating by affinity chromatography, disruption and componential characterization of serotonergic nerve endings from mammalian brain. The findings should aid in an understanding of faulty brain function and the destructive effects of hallucinogens and neurotoxins. To investigate the role of ecto-sialidase of herpes-virus transformed cells in culture, using chromatographic and specific radioactive tracer techniques to trace the effects of this enzyme on the metabolism of cell surface sialic acid and the controlling influence of the latter on ecto-enzymes involved in the breakdown of the neural cell guanyl cyclase activator, acetylcholine. This information should be helpful in approaching a rational therapy for virally induced neuropathies and neuro-oncogenicity.
