High levels of low density lipoprotein (LDL), cholesterol and triglycerides have been associated with an increase in cardiovascular disease. Drugs such as cholesterol-lowering statins and triglyceride-lowering fibrates have led to a reduction in coronary heart disease. Although current drugs have enjoyed some success, a need exists for improved lipid management and reduced side effects. Zygogen is developing a novel in vivo approach to identifying potential lipid-lowering drugs using Zebrafish, called Z-Lipotrack. Lipid processing is highly conserved in the Zebrafish. Because Zebrafish larvae are essentially transparent, lipid processing can be readily observed in the whole organism, with the aid of fluorescent lipid reporters. The goal of the proposed research is to develop Z-Lipotrack technology for use in high throughput compound screening, with the ultimate aim of discovering better drugs for lowering lipid levels. The proposed work will validate Z-Lipotrack as a compound screening tool. This includes testing additional control compounds, characterizing compounds identified in a small but diverse library of marketed drugs, and quantifying the fluorescent read-out in an automated fashion. Due to the high fecundity of Zebrafish, high throughput drug screening using Zebrafish larvae is feasible and could dramatically increase the chances of finding important new drugs.
| Hama, Kotaro; Provost, Elayne; Baranowski, Timothy C et al. (2009) In vivo imaging of zebrafish digestive organ function using multiple quenched fluorescent reporters. Am J Physiol Gastrointest Liver Physiol 296:G445-53 |
