A Screen for Identifying Insomnia Genes.

识别失眠基因的屏幕。

• 批准号: 10228112
• 负责人: Alex C Keene
• 金额: $ 1.45万
• 依托单位: FLORIDA ATLANTIC UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-15 至 2021-08-06
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10228112
• 关键词: Acute; Address; Affect; Aggressive behavior; Alleles; Anatomy; Animal Model; Architecture; Atlases; Automobile Driving; Behavioral; Biological Models; Brain; Brain imaging; Brain region; CRISPR screen; CRISPR/Cas technology; Calcium; Clustered Regularly Interspaced Short Palindromic Repeats; Collaborations; Communities; Development; Disease; Enzymes; Evolution; Exhibits; Exploratory/Developmental Grant for Diagnostic Cancer Imaging; Eye; Fatigue; Fishes; Functional Imaging; Gene Expression; Gene Transfer Techniques; Genes; Genetic; Genetic Models; Head; Health; Hour; Human; Hyperphagia; Image; Impaired cognition; Individual; Individual Differences; Investigation; Measures; Medicine; Melatonin; Metabolic dysfunction; Methodology; Mexican; Modeling; Mutagenesis; Neuroanatomy; Neurons; Neuropeptides; Neurophysiology - biologic function; Obesity; Periodicity; Phenotype; Physiology; Play; Population; Preparation; Process; Protocols documentation; Research; Resources; Rivers; Role; Scanning; Sleep; Sleep Deprivation; Sleep Disorders; Sleep disturbances; Sleeplessness; Stream; Structure; Surface; System; Transgenic Organisms; Up-Regulation; Variant; Vertebrates; base; circadian; comparative; experimental study; genetic manipulation; genetic technology; genetic variant; high throughput screening; hypocretin; implementation facilitation; in vivo; insight; mutant; nervous system disorder; neural circuit; neuromechanism; neuroregulation; novel; relating to nervous system; response; screening; sleep regulation; tool

Project Summary Evolutionary medicine leverages the power of naturally occurring phenotypic differences derived through adaptation to investigate genetic mechanisms underlying diseases, including neurological disorders. The Mexican cavefish exhibits a dramatic evolution of sleep loss compared to ancestral surface fish of the same species, providing a unique and powerful model to identify genetic factors regulating sleep. The proposed experiments will implement genetic technology in Mexican cavefish to identify novel regulators of naturally occurring insomnia-like phenotypes in cavefish. This proposal will also apply a newly developed neuroanatomical brain atlas and whole-brain calcium imaging to determine how novel sleep genes impact brain structure and function. These experiments will provide critical insight into the mechanistic basis of sleep regulation and identify naturally occurring genetic variants that contribute to sleep regulation. Further, the genetic tools and methodology established in these studies will provide valuable resources that can be applied to address questions beyond the scope in this proposal, including diseases such as eye-degeneration, obesity, hyperphagia and aggression that are commonly studied in this system.

项目摘要 进化医学利用自然发生的表型差异的力量， 适应调查遗传机制潜在的疾病，包括神经系统疾病。的 墨西哥洞穴鱼表现出一个戏剧性的演变睡眠损失相比，祖先的表面鱼相同 物种，提供了一个独特的和强大的模型，以确定调节睡眠的遗传因素。拟议 实验将在墨西哥洞穴鱼中实施遗传技术，以确定自然环境中的新调节因子。 在洞穴鱼类中出现失眠样表型。该提案还将采用新开发的 神经解剖脑图谱和全脑钙成像，以确定新的睡眠基因如何影响 大脑结构和功能这些实验将为睡眠的机械基础提供重要的见解 调节和识别有助于睡眠调节的自然发生的遗传变异。此夕h 在这些研究中建立的遗传工具和方法将提供可应用的宝贵资源 解决超出本提案范围的问题，包括眼睛退化，肥胖， 嗜食和攻击性，这是该系统中经常研究的。