Ecophysiological genomics of fat oxidation and renal vasoconstriction during acute dehydration

每年有数百万人直接死于脱水，还有无数人遭受生理上的痛苦。 和认知障碍。虽然提供安全饮用水是最终的解决方案，但这并不总是 立即可能(例如，疾病、水污染、自然灾害等)。尽管工作了几十年 旨在了解脱水的病理生理学，脱水相关发病率的存在和 死亡率的存在表明，促进新理解的替代研究策略迫在眉睫 需要的。一种这样的替代策略包括阐明脱水的基因组结构。 事实上，从表面上看，理解建筑与人类健康和医学作为基因组是相关的 疾病表型的潜在机制通常建议新的治疗策略(例如，在糖尿病中，许多 癌症和冠状动脉疾病)。拟议的多学科研究方法旨在描述 实验室新出现的啮齿动物模型中脱水耐受性的生理学和基因组结构 还有野生动物。具体地说，将描述生理学的特征，以及先前确定的与 肾血管收缩中代谢水的产生将受到药理学和遗传学的控制。 利用野生仙人掌鼠同时存在于沙漠和非沙漠地区这一事实的实地研究 南加州。抗旱性存在自然变异。外显子组捕获和RADseq测序将 对来自多个种群的所有动物进行研究，并将使用种群基因组方法来 确定可能导致耐旱性变异的基因和基因组区域。团结在一起， 拟议的工作将为影响数百万人的疾病提供重要而新颖的见解。 事实上，了解脱水的生理学和基因组基础是关键的第一步 通向治疗和干预的途径。

Millions of people die every year as a direct result of dehydration, with countless others suffering physiologic and cognitive impairment. While providing safe drinking water is the ultimate solution, this is not always immediately possible (e.g., illness, water contamination, natural disasters, etc.). Despite decades of work aimed at understanding the pathophysiology of dehydration, the existence of dehydration-related morbidity and mortality exists suggests that alternative research strategies promoting new understanding are urgently needed. One such alternative strategy includes the elucidation of the genomic architecture of dehydration. Indeed, understanding architecture is, prima facie, relevant to human health and medicine as the genomic mechanisms underlying disease phenotypes often suggest novel treatment strategies (e.g., in diabetes, many cancers, and coronary artery disease). The proposed multidisciplinary research approach aims to characterize the physiology and genomic architecture of dehydration tolerance in an emerging rodent model in laboratory and wild animals. Specifically, physiology will be characterized, and previously identified pathways related to metabolic water production in renal vasoconstriction will be pharmacologically and genetically manipulated. Field studies that leverage the fact that wild cactus mice exist in both desert and non-desert locations in Southern California. Natural variation in drought tolerance exists. Exome capture and RADseq sequencing will be performed on all animals from multiple populations, and a population genomic approach will be used to identify genes and genomic regions likely responsible for variation in drought tolerance. Together, the proposed work will provide important and novel insights into a condition impacting millions of individuals. Indeed, understanding the physiology and genomic underpinnings of dehydration is the critical first step in the pathway leading to treatments and interventions.