The proposed research would investigate the feasibility of a method for direct isolation and cloning of genes associated with states of disease, cell differentiation, or metabolic induction. Phase I studies will focus on steps in the process that currently limit the widespread use of substractive nucleic acid hybridization as a means of isolating the target genes. In Phase II this technology will be integrated and optimized to allow the cloning of any gene that is active in one cell type but not another.