Protecting tissues from oxidative damage
Edward H. Snell, Ph.D

Cells naturally produce reactive oxygen species both as metabolic by-products and for the signaling of certain cellular processes. Excessive reactive oxygen species (free radicals) are scavenged by antioxidant defenses that protect tissue from oxidative damage. The structure and mechanism for how this occurs within the cells is known. Outside of the cells, the free radical scavenger, extracellular superoxidedismutase (ECSOD), in partnership with fibulin-5 acts as the defense. The structure of these two proteins and how they interact is unknown.  ECSOD protects against vascular disease, and acts as the only free radical scavenger in the brain and lungs. In addition to vascular disease, it is important in areas as diverse as lung disease, diabetes, and degenerative neurological problems associated with ageing. Fibulin-5 anchors ECSOD but is also associated with macular degeneration, another complication of diabetes and ageing. We aim to determine the structures and there by understand the mechanism and failure modes of those protective mechanisms. With structural and mechanistic knowledge, we will provide the first step toward rational drug design for effective medical intervention.