VISUALIZATION OF LIPID METABOLISM AND SIGNALING IN THE ZEBRAFISH

Work in my laboratory utilizes the zebrafish, Danio rerio, to visualize biochemical processes in living embryos by exploiting their accessibility and optical clarity. Specifically, the laboratory has focused on studying phospholipase A2 (PLA2) activity and cholesterol transport in the developing embryo. PLA2 activity is known to play a role in a host of physiological processes, most notably inflammation, and in cancer. Despite these findings, little is known about the role of PLA2 in cell signaling events important during embryonic development. A novel aspect of this work is that it examines the regulation of lipid metabolism in vivo by feeding embryos fluorescent lipids and visualizing their uptake, and processing using time-lapse microscopy. We are also engaged in a large scale mutagenesis screen to identify mutations which alter PLA2 activity and/or cholesterol metabolism, as revealed by these fluorescent lipids. We expect that this approach will lead to the identification of genes that regulate physiological and developmental processes that cannot be assayed using conventional screening strategies. Examples include genes that regulate lipid and prostaglandin metabolism, intestinal and liver transport and development of the biliary tract. Identification of these genes has important implications for cancer research and research related to diseases of the liver, intestine and cardiovascular system.