This SBIR Phase I project will employ a new bioinformatic tool to combine in silico gene mapping and comparative genomics for predicting designer rat strains that mimic human disease. The genome sequencing projects are bringing new molecular tools to both the pharmacologist and toxicologist. However, each species has its own biological foundations that may lead to misclassification of drug efficacy resulting in the high failure rates of compounds late in clinical trials. Therefore, a need exists within the pharmaceutical and academic communities for more precise animal model systems that better reflect the specific components of a clinically defined disease. PhysioGenix, Inc. will accomplish this by matching the traits of human diseases to a panel of designer rat strains at both the phenotypic and genomic levels (note that this is a paradigm shift from the standard practice of matching animal models to human diseases based solely on phenotype). Proof of principle will be demonstrated by phenotyping designer rats modeled for type 2 diabetes and show that strains like these will be ideal for drug screening, gene discovery and molecular target validation. Phase II efforts will expand the designer rat panel to mimic different diseases and contribute to PhysioGenix' knowledge warehouse.