SELECTING BIOMARKERS FOR THE MOLECULAR DIAGNOSIS OF SLEEPINESS

描述（由申请人提供）：牺牲睡眠以满足我们24小时社会的需求是一种常见的经历。目前的估计显示，作为一个社会，我们的睡眠时间比40年前平均少2小时。这种程度的睡眠限制会导致负面的健康结果，足以产生认知缺陷，注意力下降，并与交通和职业事故的风险增加有关。不幸的是，没有简单的可量化的标志物可以在不良后果变得明显之前检测出过度嗜睡的个体。为了解决这个问题，我们已经开发了一种简单而有效的策略，用于使用遗传和药理学工具来识别嗜睡的生物标志物，该工具将模式生物果蝇中的睡眠驱动与唤醒时间分离。在这个提议中，我们将从我们的果蝇生物标志物数据库中选择基因来开发一种非侵入性的工具，可以用于人类嗜睡的分子诊断。我们将鉴定对急性睡眠丧失有反应的基因，然后确定这些生物标志物在阻塞性睡眠呼吸暂停综合征患者中是否发生了改变。 睡眠不足会对代谢过程、内分泌功能和免疫产生不利影响，并可能增加个体对严重疾病的易感性，包括肥胖症、II型糖尿病和冠心病等。开发嗜睡的分子诊断工具将有助于识别和治疗普通人群和危重患者人群中的嗜睡。

DESCRIPTION (provided by applicant): It is a common experience to sacrifice sleep to meet the demands of our 24-h society. Current estimates reveal that, as a society, we sleep on average 2 h less than we did 40 years ago. This level of sleep restriction results in negative health outcomes and is sufficient to produce cognitive deficits, reduced attention, and is associated with increased risk for traffic and occupational accidents. Unfortunately, there is no simple quantifiable marker that can detect an individual who is excessively sleepy before adverse outcomes become evident. To address this issue we have developed a simple and effective strategy for identifying biomarkers of sleepiness using genetic and pharmacological tools that dissociate sleep drive from wake time in the model organism Drosophila melanogaster. In this proposal we will choose select genes from our Drosophila Database of Biomarkers to develop a noninvasive tool that can be used for the molecular diagnosis of sleepiness in humans. We will identify genes that are responsive to acute sleep loss then determine if these biomarkers are altered in patients with obstructive sleep apnea syndrome.PROJECT NARRATIVE Sleep loss adversely effects metabolic processes, endocrine functions, and immunology and may increase the susceptibility of individuals to serious diseases, including obesity, type II diabetes and coronary heart disease to name a few. Developing tools for the molecular diagnosis of sleepiness will assist with the identification and treatment of sleepiness in the general population and in critical patient populations.