Project 3
Project 3
批准号:
8479255
负责人:
Alexander Martinus Van der Linden
金额:
$30.23万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
关键词:
AffectAfferent NeuronsAlzheimer&aposs DiseaseAnimal ModelAnimal TestingAnimalsBehaviorBehavioralBiologicalBiological AssayBiological ClocksBiological ModelsBody TemperatureBody Temperature ChangesBrainCaenorhabditis elegansCircadian RhythmsComputer softwareCoupledCuesExhibitsGene ComponentsGene ExpressionGene Expression ProcessGenesGeneticGenetic ModelsGenetic ScreeningGenomicsHourHumanHypoxiaImageLeadLightMapsMolecularMolecular ProfilingMoodsMorbidity - disease rateMutationNematodaNeural PathwaysNeurosciencesOrganismOutputPathway interactionsPatientsPeriodicityPeripheralPhysiologicalPhysiologyPreventionProcessRegulationResearchSensorySensory ProcessSeveritiesSignal TransductionSleepStrokeSystemTaxesTechniquesTemperatureTemperature SenseTherapeutic InterventionTimeTissue-Specific Gene ExpressionTissuesWorkcircadian pacemakercyclic-nucleotide gated ion channelsdesigninsightmRNA taggingmutantnervous system disorderneural circuitneurobehavioralnext generationresponsesuprachiasmatic nucleustooltreatment strategy
中文摘要
线虫生物钟的温度控制
日常(昼夜)节律控制着人类行为和生理的多个方面(例如,睡眠、身体
体温)和这些节律的中断会导致或影响大多数神经系统的严重程度
中风和阿尔茨海默氏症等疾病。这些昼夜节律是由我们大脑中的时钟驱动的
以及可能被日常光线和/或温度循环缠绕的身体。深入的分析已经确定
在人类和大多数模式生物中,组成这些光携带时钟的生理机制
研究过,但温度信息如何控制这些时钟尚不清楚。我们的研究已经确立了
线虫线虫作为一种强大的遗传模型系统研究线虫的温度控制
钟。在这项拟议的研究中,我们将使用遗传和基因组方法以及实时成像
在线虫中研究温度控制的分子机制和神经通路
生物钟的一部分。特定目标1将开发一种新的实时成像系统,用于记录和
对自由活动的线虫行为和基因表达的昼夜节律性进行量化。这一成像
为时钟突变体的突变分析和遗传筛选奠定了基础。具体目标2将定义
将温度信息传输到时钟的感觉神经元类型(S)。这将有助于理解
将环境信息处理并整合到时钟中的感觉通路。具体目标3将
定义时钟的分子组成。这些组件预计将针对核心时钟进行编码
处理从核心时钟到时钟输出基因的温度信息的基因和组件。
特定目标4将通过mRNA测序来识别在单一感觉神经元类型中表达的昼夜节律基因。
线虫时钟Will调控的全套感觉基因的鉴定
确定处理环境的基因差异表达的行为后果
将信息发送到时钟。深入了解生物钟的内部工作原理和
对昼夜节律的影响应该为我们提供新的治疗或预防
昼夜节律紊乱的神经行为后果。
英文摘要
Temperature control of the C. elegans circadian clock
Daily (circadian) rhythms control multiple aspects of human behavior and physiology (e.g. sleep, body
temperature) and disruption of these rhythms can either cause or affect the severity of most neurological
disorders such as stroke and Alzheimer's disease. These circadian rhythms are driven by clocks in our brain
and body that can be entrained by daily light and/or temperature cycles. In depth analyses have identified
the physiological mechanisms comprising these light-entrained clocks in humans and most model organisms
studied, but how temperature information controls these clocks is unclear. Our research has established the
nematode Caenorhabditis elegans as a powerful genetic model system to study temperature control of the
clock. In this proposed research, we will use genetic and genomic approaches as well as real-time imaging
in C elegans to investigate the molecular mechanisms and neural pathways underlying temperature control
ofthe circadian clock. Specific Aim 1 will develop a new real-time imaging system for recording and
quantifying circadian rhythmicity in behavior and gene expression in freely moving C elegans. This imaging
will be useful for mutant analysis and genetic screening of clock mutants. Specific Aim 2 will define the
sensory neuron types that transmit temperature information to the clock(s). This will aid in understanding the
sensory pathways that process and integrate environmental information to the clock. Specific Aim 3 will
define the molecular components ofthe clock. These components are expected to encode for core-clock
genes and components that process temperature information from the core-clock to clock-output genes.
Specific Aim 4 will identify circadian genes expressed in single sensory neuron types with mRNAsequencing.
Identification ofthe complete set of sensory genes regulated by the C elegans clock will
determine the behavioral consequences of differential expression of genes that process environmental
information to the clock. Understanding the inner workings ofthe circadian clock in great depth and the
impacts on circadian time keeping should provide us with new avenues of treatment or prevention of
neurobehavioral consequences of disrupted circadian timing.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Cellular and Molecular Imaging Core
-
批准号:10666523
-
项目类别:
-
资助金额:$12.51万
-
财政年份:2022
-
负责人:Alexander Martinus Van der Linden
-
依托单位:
Cellular and Molecular Imaging Core
-
批准号:10418522
-
项目类别:
-
资助金额:$12.43万
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财政年份:2022
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负责人:Alexander Martinus Van der Linden
-
依托单位:
Molecular Imaging and Media Core
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批准号:10194515
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项目类别:
-
资助金额:$8.32万
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财政年份:2012
-
负责人:Alexander Martinus Van der Linden
-
依托单位:
Temperature control of the C. elegans circadian clock
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批准号:8445997
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项目类别:
-
资助金额:$19.1万
-
财政年份:2012
-
负责人:Alexander Martinus Van der Linden
-
依托单位:
Temperature control of the C. elegans circadian clock
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批准号:8536970
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项目类别:
-
资助金额:$13.61万
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财政年份:2012
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负责人:Alexander Martinus Van der Linden
-
依托单位:
Project 3
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批准号:8539822
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项目类别:
-
资助金额:$23.94万
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财政年份:--
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负责人:Alexander Martinus Van der Linden
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依托单位:
Molecular Imaging and Media Core
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批准号:9360971
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项目类别:
-
资助金额:$7.43万
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财政年份:--
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负责人:Alexander Martinus Van der Linden
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依托单位:
海外基金