Grant: Operating Grant

Obesity has now been identified as the principal risk factor for heart disease, the leading cause of death in Western societies. In 2004, 32.1% of all Canadian deaths were attributed to cardiovascular diseases, and an additional 3.5% died of diabetes-related disorders. Understanding the regulatory processes that control fat and cholesterol metabolism is therefore essential for dissecting the connection between obesity and the onset of atherosclerosis, diabetes, heart disease and other serious disorders. The absence of a comprehensive model that could explain these relationships originates from our incomplete understanding of the complex signaling pathways and feedback mechanisms that govern the physiology of fat tissue and cholesterol homeostasis. To approach these problems in a simple and highly tractable system, Dr. King-Jones studies evolutionary conserved pathways controlling lipid and cholesterol metabolism in a classic model organism, Drosophila melanogaster. Specifically, Dr. King-Jones studies a class of important regulatory proteins called nuclear receptors. Members of this protein family regulate transcription upon binding to small fat-soluble compounds such as steroid hormones, nutrient metabolites or toxins. Dr. King-Jones currently examines a gene called DHR96, a close relative of the human nuclear receptor genes SXR and CAR, because it appears to regulate critical aspects of cholesterol metabolism. These studies could advance our understanding of metabolic pathways and may shed light on similar processes in humans.