Among other factors, one underlying cause of obesity, non-insulin-dependent diabetes mellitus and cardiovascular diseases is dyslipidosis (disruption of fat metabolism), which leads to massive deposits of triglycerides in fatty tissue and of cholesterol on the artery walls. The goal of this project is to discover and explain the function of each gene and protein involved in the process of uptake, storage and mobilization of lipids (fats) by cells. The specific questions addressed by the GOLD project are the following: 1) How is the expression pattern of genes in different tissues changed by genetic defects in fat metabolism, and what are the physiological functions of these genes? 2) What lipid splitting enzymes occur in the human genome and in the genomes of model organisms (mice, yeast)? What are their structures and their functional roles in fat metabolism? Target genes of medical interest will be identified through analysis of the entire genome using microchip technology and bioinformatics. An alternative proteomic approach will make use of specific lipase inhibitors which are fluorescently labeled to isolate and identify potential lipases. Then the structure and physiological function of the new gene products will be described. Finally, the most interesting candidates will be thoroughly studied to determine their role(s) in the appearance of the diseases mentioned above and their potential medical usefulness.