DESCRIPTION (Adapted from the Applicant?s Abstract): Cells of the renal medulla are exposed to hyperosmolar NaCI and urea during the process of creating concentrated urine. This hyperosmolar environment can adversely affect cellular functions, including enzyme activities and biosynthetic processes. To adapt, renal medullary cells synthesize stress proteins and accumulate organic osmolytes. To gain greater insight into this incompletely understood process, we hypothesize that under conditions of hyperosmolar stress, programmed pathways of signaling and gene transcription are activated resulting in changes in cellular phenotype. The recent advances in RNA expression analysis using cDNA microarrays allows for large scale analyses of RNA expression. These tools in concert with bioinformatics analysis methods can provide insight into the complex coordinated changes in gene expression involved in the adaptation to stress. The research plan proposes three Specific Aims: 1) To characterize the ability of hyperosmolar urea and NaC1 to induce apoptosis or survival in murine inner medullary collecting duct mIMCD3 cells and determine the role of complement pathway inhibitors in this process; 2) To use cDNA microarrays to analyze changes in mRNA expression and identify coordinated patterns of gene expression; and 3) Validate and characterize the functional roles of key co-regulated genes. In addition to the proposed research plan, the applicant and sponsor have developed a training program involving all aspects of basic academic research that will facilitate the transition of the applicant to becoming an independent investigator.