The aim of this two-year """"""""Grand Opportunities"""""""" (""""""""GO"""""""") proposal is to construct a detailed and comprehensive profile of the molecular biology of cardiac function in a hibernating mammal. In compliance with """"""""GO"""""""" program requirements the proposed project is a convergence of expertise at the University of Minnesota involving multiple campuses and facilities including the Biomedical Genomics Center and Minnesota Supercomputing Institute in the Twin Cities, the School of Medicine, Department of Biology and the Department of Mathematics &Statistics in Duluth, and an industrial partner, Tethys Bioscience. Hibernation is a natural adaptation that allows certain mammals to survive physiological extremes that result in death in humans. The fundamental adaptation present in natural hibernators is greatly reduced body temperature, metabolism and respiration- conditions that buy precious time in cases of myocardial ischemia, traumatic injury and cardiac arrest. Our central hypothesis is that changes in hibernation-specific gene expression and lipid composition provide protection against myocardial damage normally associated with ischemia and reperfusion injury. High-throughput instrumentation and advances in computational power have placed us in a unique position to identify genes that control the hibernation phenotype and to link their expression to cardiac function under extreme conditions. We will identify genes that are expressed in active and hibernating thirteen-lined ground squirrels (Spermophilus tridecemlineatus) by high-throughput cDNA sequencing using the Roche 454 system. This massive sequencing platform will generate statistically high numbers of cDNA sequences that will be processed by the Minnesota Supercomputing Institute to determine patterns of gene expression throughout the hibernation season. Due to the importance of lipids as fuel, and as structural and signaling molecules, we will enlist the services of a corporate partner, Tethys Bioscience (www.lipomics.com), to perform a comprehensive survey of heart, white adipose tissue and serum lipids. Tethys specializes in quantifying over 450 lipid metabolites in plasma/sera and tissue. At the conclusion of this two-year project we will have a detailed molecular profile of cardiac function in mammalian hibernators and a better understanding of how this natural adaptation results in the avoidance of the pathological consequences of hypothermia, ischemia and reperfusion injury.
The aim of the research described in this proposal is to construct a detailed and comprehensive profile of the molecular biology of cardiac function in hibernating mammals. The fundamental adaptation present in natural hibernators is greatly reduced body temperature, metabolism and respiration-conditions that buy precious time in cases of myocardial ischemia, traumatic injury and cardiac arrest. Our central hypothesis is that hibernation-specific changes in gene expression and the composition of lipids provides protection against myocardial damage normally associated with ischemia and reperfusion injury.
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