The purpose of this project is to determine the molecular events involved in the biosynthesis of neutrophil and eosinophil granules and granule proteins. The project focuses on the identification and characterization of the regulatory elements affecting the expression of granule protein genes and identification and characterization of the events resulting in granule protein folding and translocation and granule formation. Our recent work has shown that the defect resulting in the disorder known as neutrophil specific granule deficiency produces similar abnormalities in eosinophils, suggesting coordinate regulation of these two granulocyte lineages at this developmental stage. Further experiments designed to characterize the molecular defect underlying this disorder are described. In a separate set of experiments, we have described a novel interaction between two eosinophil granule proteins and the prokaryotic chaperone protein, groEL, and have localized a unique binding site near the amino terminus of one of the two granule proteins. Further experiments designed to isolate and characterize the homolog mediating the folding of these granule proteins in their native locale are described.
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