Small model animals such as zebrafish and nematode have become invaluable for studying early development and for drug discovery. The zebrafish has a morphological and molecular basis of tissue and organ development that is similar to other vertebrates, including humans. Phase II research will automate the enzymatic assay developed in Phase I research for high throughput screening of small molecule compound libraries. The microplate-based zebrafish assay offers several compelling advantages, including assay time, drug delivery and drug dosage. Because zebrafish are inexpensive to breed and maintain, a statistically significant number of animals can be assayed. Phase II research will also develop complementary assays to assess effects of "hit" drugs on liver toxicity and whole animal development. Since comprehensive drug screening programs rely on a number of confirmatory assays to assess drug specificity, Phase II research will develop a family of complementary assays to fully characterize potential anti-angiogenic drugs. Analysis of complete living systems, before proceeding to complex living systems, such as the mouse, will streamline the drug development process and dramatically reduce costs. PROPOSED COMMERCIAL APPLICATIONS: By providing a family of simple, rapid and inexpective assays for identifying and characterizing angiogenesis inhibitors, the zebrafish assays will facilitate the drug development process for a variety of diseases, including cancer, and heart, eye, rheumatic and skin diseases.