CAREER: Protein Metabolism During Mammalian Hibernation

在地松鼠冬眠期间，核心体温可能低至-2摄氏度，心率可能从每分钟200-250次左右下降到每分钟3-4次不稳定的心跳，代谢率可能接近正常速率的1/100。 冬眠的惊人代谢抑制意味着关键的代谢活动，如蛋白质合成和降解，必须可逆地关闭。 然而，如果一个人要生存，就需要维持蛋白质库。 生物化学和分子策略将被用来检查蛋白质代谢被抑制的机制以及这种抑制的含义。 这项研究将具体解决如何在冬眠期间大量的蛋白质合成起始下调的机制。 还将研究一种新的蛋白质合成启动机制的作用，这种机制可以通过增加应激蛋白的产生来促进冬眠的生存。 最后，将研究蛋白质降解如何被抑制的机制。 这项研究不仅将回答有关蛋白质代谢等基本过程如何被抑制同时仍然允许生存的基本问题，而且还应该为未来利用这些自然教训进行人类健康治疗的应用努力提供见解。例如，更好地理解冬眠可能对设计心脏功能障碍，肌肉废用性萎缩和肾衰竭的治疗方法具有深远的意义。 本科和研究生教育将是这项研究的一个组成部分。 这项赠款的一个推广部分将是与联合国志愿人员组织电视台联合制作一个名为“沙漠幸存者”的地方儿童电视节目。 该计划将展示当地的植物群和动物群，旨在促进当地小学的科学素养。

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.