My research will explore the molecular mechanisms that allow some animals to withstand oxygen deprivation and replenishment. While heart attacks and strokes cause severe damage by cutting off the oxygen supply to tissues, a condition known as hypoxia, the rapid reintroduction of oxygen can also be deleterious to cells and their components. Yet some organisms are surprisingly resistant to damage from hypoxia and reoxygenation, including the free-living nonparasitic worm C. elegans and a type of hibernating ground squirrel, both of which face fluctuating oxygen levels in their natural environments. I will identify the genes that provide these two organisms with a tolerance for oxygen deprivation and reintroduction. As a postdoctoral fellow, I discovered and characterized genes involved in the worm's ability to withstand reoxygenation. Now, I will identify genes that confer resistance to hypoxia in squirrel cells and will search for genes that do the same in C. elegans. Ultimately, I will test these "hypoxia tolerance" genes in mouse and human cells to determine whether they can protect these normally sensitive cells against hypoxic damage—work that could lead to new strategies for limiting the damage from heart attacks and stroke in humans.