Identification of Biomarkers Reflecting Homeostatic Sleep Drive

反映稳态睡眠驱动力的生物标志物的鉴定

• 批准号: 10285978
• 负责人: Clark Jeffrey Rosensweig
• 金额: $ 3.43万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10285978
• 关键词: Affect; Anatomy; Animals; Area; Behavior; Behavior monitoring; Biology; Brain; Brain region; CRISPR/Cas technology; Candidate Disease Gene; Characteristics; Circadian Rhythms; Detection; Drosophila melanogaster; Electroencephalogram; Engineering; Female; Future; Gene Components; Gene Expression; Gene Expression Profiling; Genes; Goals; Heart; Homeostasis; Imaging Device; Investigation; Knowledge; Length; Link; Luciferases; Mammals; Molecular; N-Methyl-D-Aspartate Receptors; Neurons; Optics; Plant Roots; Population; Process; Proteins; RNA Interference; Recovery; Reporter; Reporting; Role; Secondary to; Signal Transduction; Sleep; Sleep Deprivation; Specificity; System; Time; Tissues; Transcript; Transgenic Organisms; Validation; Wakefulness; analog; base; biological adaptation to stress; bioluminescence imaging; biomarker identification; candidate marker; circadian; circadian pacemaker; experience; experimental study; fly; gene discovery; genomic locus; improved; in vivo; in vivo imaging; in vivo monitoring; interest; luciferin; male; molecular clock; molecular marker; novel; novel strategies; promoter; real time monitoring; response; screening; tool; tool development; transcriptome sequencing; transcriptomics

Two interacting processes, the circadian clock and a homeostatic sleep drive, which reflects both the quality and quantity of waking experience, regulate sleep. The circadian clock has been heavily studied and the molecular process underlying it is well understood. The sleep homeostat, on the other hand, is poorly understood and our knowledge of the molecular processes governing it is incipient at best. Discovery of the gene period, which encodes an integral component of the molecular clock and displays oscillatory expression reflecting normal clock function, allowed for real-time monitoring of the clock's molecular mechanism in vivo using a bioluminescent luciferase reporter (per-luc). In contrast, the best marker of sleep drive is electroencephalogram delta band power, which neither completely reflects sleep drive nor serves as a functional component of the sleep homeostat. Thus, the primary goal of this project is to use a specific set of parameters defining an ideal homeostatic marker to actually identify markers of homeostatic sleep drive. Previous attempts to identify genes with a role in the sleep homeostat through transcriptomics have largely suffered from a lack of specificity. Substantial changes in gene expression can often be observed in specific circuits at times when global profiling reveals naught. This proposal leverages the Allada lab's expertise in gene expression profiling of small, genetically defined populations of neurons to identify transcripts that reflect changes in homeostatic drive in sleep relevant areas of the fly brain. In addition, I am proposing several novel strategies to improve detection of homeostatic genes by eliminating circadian influence and manipulating waking experience prior to homeostatically driven recovery sleep. Candidate transcripts will be subjected to secondary screening to eliminate genes that do not play a functional role in homeostatic drive. Finally, I propose to develop novel tools for in vivo monitoring of the molecular process governing sleep drive to facilitate future inquiry into the mechanisms underlying sleep.

两个相互作用的过程，生物钟和体内平衡睡眠驱动，这两个过程都反映了

项目成果

Circadian programming of the ellipsoid body sleep homeostat in Drosophila.

• DOI: 10.7554/elife.74327
• 发表时间: 2022-06-23
• 期刊: ELIFE
• 影响因子: 7.7
• 作者: Andreani, Tomas;Rosensweig, Clark;Sisobhan, Shiju;Ogunlana, Emmanuel;Kath, William;Allada, Ravi
• 通讯作者: Allada, Ravi