权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Ecophysiological genomics of fat oxidation and renal vasoconstriction during acute dehydration

急性脱水期间脂肪氧化和肾血管收缩的生态生理基因组学

基本信息

批准号：
10449273
负责人：
Matthew David MacManes
金额：
$ 35.24万
依托单位：
UNIVERSITY OF NEW HAMPSHIRE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2025-06-30
项目状态：
未结题

项目摘要

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.

每年有数百万人直接死于脱水，还有无数人遭受生理性脱水。和认知障碍。虽然提供安全的饮用水是最终的解决办法，但这并不总是立即可能的（例如，疾病、水污染、自然灾害等）。尽管人们已经努力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，死亡率的存在表明，促进新认识的替代研究战略是迫切的， needed.一种这样的替代策略包括阐明脱水的基因组结构。事实上，理解建筑是，初步看来，有关人类健康和医学的基因组疾病表型的潜在机制通常提示新的治疗策略（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表征一种新啮齿动物脱水耐受模型的生理学和基因组结构和野生动物。具体而言，生理学将被表征，并且先前确定的与以下相关的途径：肾血管收缩中的代谢水产生将被抑制和遗传操纵。利用野生仙人掌鼠存在于沙漠和非沙漠地区这一事实的实地研究，南加州。耐旱性存在自然变异。外显子组捕获和RADseq测序将对来自多个群体的所有动物进行，并将使用群体基因组方法确定可能导致耐旱性变异的基因和基因组区域。统称拟议的工作将为影响数百万人的疾病提供重要和新颖的见解。事实上，了解脱水的生理学和基因组基础是研究脱水的关键的第一步。导致治疗和干预的途径。

项目成果

期刊论文数量（17）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Divergent selection and drift shape the genomes of two avian sister species spanning a saline–freshwater ecotone

DOI：
10.1002/ece3.5804
发表时间：
2018-06
期刊：
Ecology and Evolution
影响因子：
2.6
作者：
J. Walsh;Gemma V. Clucas;M. MacManes;W. K. Thomas;Adrienne I. Kovach
通讯作者：
J. Walsh;Gemma V. Clucas;M. MacManes;W. K. Thomas;Adrienne I. Kovach

A total crapshoot? Evaluating bioinformatic decisions in animal diet metabarcoding analyses.

DOI：
10.1002/ece3.6594
发表时间：
2020-09
期刊：
Ecology and evolution
影响因子：
2.6
作者：
O'Rourke DR;Bokulich NA;Jusino MA;MacManes MD;Foster JT
通讯作者：
Foster JT

Limited Evidence for Parallel Evolution Among Desert-Adapted Peromyscus Deer Mice.

DOI：
10.1093/jhered/esab009
发表时间：
2021-05-24
期刊：
The Journal of heredity
影响因子：
0
作者：
Colella JP;Tigano A;Dudchenko O;Omer AD;Khan R;Bochkov ID;Aiden EL;MacManes MD
通讯作者：
MacManes MD

When the tap runs dry: the physiological effects of acute experimental dehydration in Peromyscus eremicus.