The regulation of mitochondrial function by nitrite in ischemia/reperfusion

Description of projects available to graduate students:
Reactive nitrogen species (nitric oxide, nitrite, nitrate) are ubiquitous in the body and present in the environment and diet. These species have been shown to regulate mitochondrial function and mediate cytoprotection in a number of cardiovascular diseases.The goal of our lab is to determine the mechanisms by which reactive nitrogen species regulate mitochondrial function and signal through the organelle in order to ultimately confer protection in the heart.
Specifically, the molecule nitrite has been shown by number of labs to mediate acute and delayed cytoprotection when administered before an episode of myocardial infarction. Previous data from our lab suggests that this protection is due to a nitrite-dependent decrease in mitochondrial reactive oxygen species generation and is dependent on the presence of myoglobin in the heart. This project will determine the mechanism by which myoglobin and nitrite interact to modulate mitochondrial reactive oxygen species generation. The project will encompass studies to determine the biochemical mechanisms of interaction between myoglobin and nitrite as well as molecular studies using myoglobin knockout mice to determine the mechanisms by which nitrite and myoglobin modify mitochondrial proteins, leading to altered function.

Techniques graduate student will learn:
blue native gel electrophoresis, western blots, biochemical assays of mitochondrial function, cell culture, in vivo models of ischemia/reperfusion