Career Advancement Award: Physiological Regulation of Sulfate Homeostasis: Development of Techniques

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Dr. Morris's long-term research goal is to understand the regulation of sulfate homeostasis. Inorganic sulfate is a physiological ion necessary for biosynthetic reactions especially important in growth and development, and for the biologic activity and detoxification of various compounds produced in the body. Sulfated proteoglycans are components of mammalian cell membranes and tissues, and are part of the cell-recognition system necessary for cell differentiation. Serum concentrations of sulfate increase in pregnancy and are higher in fetuses and young children than in adults, consistent with an increased physiological requirement for this anion during growth and development. Capacity-limited renal reabsorption is of primary importance in the regulation of plasma concentrations of inorganic sulfate. The mechanism(s) underlying these alterations in renal transport is not known. However, the antibodies necessary to evaluate protein expression of the two renal sulfate-transport proteins are not available. As well, no available cell line exhibits sulfate transport with characteristics similar to those observed in isolated kidney-cortex preparations. Both of these tools are essential in order to evaluate the physiological regulation of sulfate reabsorption. Therefore, Dr. Morris will (1) develop methods to quantitate mRNA for the sulfate anion-exchange protein (sat-1), (2) produce antibodies to determine protein expression for the renal brush-border membrane sodium-dependent cotransport protein (NaSi-1) and the renal basolateral membrane anion-exchange transport protein (sat-1) and to characterize the specificity of these antibodies, and (3) develop a primary cell-culture system of guinea-pig proximal-tubule cells and to characterize the uptake of sulfate and other endogenous substrates in these cultured cells.