During hibernation in ground squirrels, core body temperatures may be as low as -2 degrees C, heart rates may fall from around 200-250 beats per minute to as low as 3-4 erratic beats per minute, and metabolic rates can approach 1/100th of normal rates. The amazing metabolic depression of hibernation means that critical metabolic activities like protein synthesis and degradation must be reversibly turned off. However, the maintenance of protein pools is required if one is to survive. Biochemical and molecular strategies will be employed to examine the mechanisms by which protein metabolism is depressed as well as the implications of that depression. This research will address specifically the mechanism of how the bulk of protein synthesis initiation is down-regulated during hibernation. Also studied will be the role of a novel mechanism of protein synthesis initiation that could promote the survivorship of hibernation by increasing the production of stress proteins. Finally, the mechanism of how protein degradation is depressed will be examined. This research will not only answer basic questions on how a fundamental process like protein metabolism can be depressed while still allowing for survivorship, but in addition, should provide insight for future applied efforts that exploit these natural lessons for human health therapies. For example, a better understanding of hibernation may have profound implications for designing therapies for cardiac dysfunction, muscle disuse atrophy, and kidney failure. Education at both undergraduate and graduate levels will be an integral part of this research. An outreach component of this grant will be a local, children's television show produced in conjunction with UNLV-TV entitled 'Desert Survivor'. This program will showcase the local flora and fauna and is designed to promote scientific literacy in the local elementary schools.
