Zebrafish is an excellent vertebrate model for in vivo chemical biology studies as its embryos develop externally and are transparent, allowing direct analysis of embryogenesis and organ formation at the single cell resolution. With the zebrafish genome sequence project nearly completed, this organism provides tremendous novel opportunities for addressing fundamental biological questions, modeling human diseases and discovering new drugs with tools of functional genomics and chemical biology. We are using chemical biology approaches in zebrafish to identify novel small molecules that have therapeutic applications in cancer, cardiovascular, metabolic and neurological diseases.
A unique resource for chemical genomics studies with zebrafish is the large collection of transgenic zebrafish lines at Shenzhen Graduate School of Peking University. These transgenic lines express fluorescent protein markers that label essentially every specific tissue or organ and make it possible to observe specific effect of small molecules on development in living embryos. Several small molecule libraries obtained from the in-house chemical synthesis and purification from Chinese medicines were screened with zebrafish and novel compounds that inhibit cell cycle protein CDK2, angiogenesis, GSK3beta and signal pathways including SHH and Wnt have been identified.