This award supports cooperative research in cell biology to be conducted by Paul Lazarow of Mt. Sinai School of Medicine in New York collaborating with Manuel Santos of the Catholic University in Santiago, Chile. The research will involve the study of subcellular organelles, peroxisomes, that participate in lipid metabolism and cellular respiration. The peroxisomal proteins seem to be formed from pre-existing organelles by synthesis on free ribosomes and imported into the organelle. Recently a series of human genetic disorders involving peroxisomal functions has been described. Some of these peroxisomal disorders are thought to be the consequence of a failure in the peroxisomal biogenetic mechanisms, in which the peroxisomal membrane plays an essential role. Unfor- tunately, the human peroxisomal membrane has been poorly studied: its protein composition is largely unknown, there are not antibodies available against its proteins, that can be used to study some aspects of peroxisomal biogenesis. This research will obtain a battery of polyclonal and monoclonal antibodies against the proteins of the human peroxisomal membrane, which can be used as reagents to evaluate the presence, abundance and subcellular localization of these peroxisomal proteins in fibroblasts derived from patients affected by disorders of peroxisomal biogenesis. The information obtained in this project will contribute to the knowledge of the structure, composition and function of human peroxisomes and to knowledge of the mechanism of peroxisome biogenesis. In addition, it will contribute to the under- standing of the role of peroxisome in genetic pathology.
