Role of protein hydoxylation in cellular response to hypoxia 67493

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How cells "sense" a change in ambient oxygen has long been a central question in biology. Increases (hyperoxia) or decreases (hypoxia) of oxygen in the cellular milieu impose a "stress" upon cells to which they must respond. Adaptation to changes in oxygen concentration in a cell's environment involves the initiation of gene and protein expression. The mechanism of control of these processes is dependent upon oxygen-dependent modification of protein structure and function. The proposed research supported by this NSERC Discovery Grant will lead to progress in two general areas. The first will uncover novel proteins in cultured mammalian cells that are subject to oxygen-dependent posttranslational modification. The second will be to further characterize the role of these proteins in cellular survival of oxygen stress. The focus will be on adaptation to hypoxic conditions. All organisms encounter changes in ambient oxygen to a greater or lesser extent. In humans, adaptation to high altitudes and ischemia (cessation of blood flow to organs and tissues, such as during cardiac arrest, stroke or organ transplant) requires the ability to respond to hypoxia.