The long-term objective of this research proposal is to understand the structural basis of glomerular filtration and possibly to define the structural & biochemical events leading to proteinuria in various disease states. Emphasis is laid on the molecular biology of the various components of the glomerular capillary wall, all of which probably determine some aspects of the permeability. The aims which are included in the present proposal are a) to isolate, characterize & study the synthesis of heparan sulfate proteoglycan b) to determine the chemical nature of the slit diaphragm and precisely define its role in glomerular permeability c) to isolate, characterize sialoglycoproteins of the epithelium & subsequently define its role in attachment/detachment processes & in events leading to proteinuria. The techniques involved in the present investigation would be cytochemistry, immunochemistry, autoradiography, gel electrophoresis, column chromatography and organ perfusion. In initial studies the tissues from the normal animals will be obtained. In later studies the experimental models like nephrotic, nephritic & diabetic rats and lupus rats and lupus mice will be employed.