Analysis of clock proteins in their non-circadian roles
分析时钟蛋白的非昼夜节律作用
基本信息
- 批准号:7900653
- 负责人:
- 金额:$ 7.86万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-08-15 至 2011-01-31
- 项目状态:已结题
- 来源:
- 关键词:Advanced Sleep Phase SyndromeAllelesAnimal ModelAnimalsBehaviorBehavioralBindingBiochemicalBiochemical GeneticsBiochemistryBiological ModelsBiomedical ResearchBrainCell NucleusCellsChronobiologyCircadian RhythmsClock proteinCollectionComplexCourtshipCytoplasmDataDefectDevelopmentDietDiseaseDrosophila genusDrosophila melanogasterDrug SensitizationEventFeedbackFemaleFertilityFiberFoodFoundationsFreezingGene ExpressionGene ProteinsGenesGeneticGoalsGuidelinesHandHeadHealthHomeostasisHomologous GeneHumanImmunoprecipitationInsectaKnowledgeLaboratoriesLeadLearningLifeLife Cycle StagesLightLinkMalignant NeoplasmsMammalsMapsMass Spectrum AnalysisMeasuresMessenger RNAMetabolicMetabolic PathwayMethodsMissense MutationModelingMolecularMutationNeuraxisNuclearNutrientNutritionalNutritional statusOocytesOogenesisOrganOvarianOvarian FollicleOvaryParticipantPathologyPathway interactionsPatternPeripheralPhasePhenotypePhysiologicalPhysiological ProcessesPhysiologyPlayPrincipal InvestigatorProcessProductionProtein AnalysisProtein-Restricted DietProteinsProteomicsReagentRecoveryRegulationReportingReproductionResearchResearch PersonnelRoleSamplingScientistSignal PathwaySignal TransductionSiteSleepSleep DisordersStretchingStructureSurfaceSystemTestingTimeTissuesUnited States National Institutes of HealthVertebratesWorkbasecircadian pacemakercomparativeeggflygene functionhuman diseaseimmunocytochemistryindexinginsightinterestmutantnovelnull mutationnutritionprotein complexresearch studyresponsetooltrait
项目摘要
Circadian clocks are evolutionary conserved coordinators of behavioral and physiological
processes. Malfunctions of circadian clocks in humans lead to serious pathologies such as sleep
disorders and cancer. Circadian timekeeping is accomplished by molecular feedback loops that
involve several clock genes and their proteins. The role of two genes period(per)and timeless(tim)
has been well established in the clock feedback loop, which operates in the model organism
Drosophila melanogaster. The products of these two genes, proteins PER and TIM,translocate to
cell nuclei and are subsequently degraded; both events are essential for clock function.
Surprisingly, in the ovary, these proteins behave differently. Their levels do not cycle; instead, they
remain stable and cytoplasmic at all times. We have evidence that non-circadian expression of
PER and TIM in the ovary may have important functions in the modulation of egg production. We
hypothesize that clock genes may be interacting with components of signaling pathways that
govern metabolic homeostasis and nutrient allocation. We propose to use biochemical and genetic
tools to test this hypothesis in two specific aims. First, we will study genetic and biochemical
interactions of PER and TIM in the ovary and test their functional significance using fecundity
related phenotypes. Second, we will perform protein interaction screens to identify novel proteins
that may interact with cytoplasmic PER and TIM. Results obtained in this study will give us
important insights into the functional significance of non-circadian expression of clock proteins.
There is increasing evidence that genes that were thought to act exclusively as clock components
have other important pleiotropic roles. They act in a non-circadian manner in both fly and mammals.
Therefore, understanding the non-circadian functions of clock genes in a model organism should
provide valuable insights into similar processes related to human health.
生物钟是行为和生理的进化保守协调者
流程.人体生物钟的故障会导致严重的疾病,如睡眠
疾病和癌症。昼夜节律计时是通过分子反馈回路来实现的,
涉及几个时钟基因及其蛋白质。两个基因的作用时期(每)和永恒(蒂姆)
在生物模型中运作的时钟反馈回路中,
果蝇这两个基因的产物,蛋白质PER和TIM,易位到
细胞核并随后降解;这两个事件对于时钟功能都是必不可少的。
令人惊讶的是,在卵巢中,这些蛋白质的行为不同。它们的水平不会循环;相反,它们
始终保持稳定和细胞质。我们有证据表明,非昼夜表达的
卵巢中的PER和TIM可能在调节卵子生产中起重要作用。我们
假设时钟基因可能与信号通路的组分相互作用,
控制着代谢平衡和营养分配。我们建议使用生物化学和遗传学
工具来测试这一假设在两个特定的目标。首先,我们将研究遗传和生物化学
卵巢中PER和TIM的相互作用,并使用生殖力测试其功能意义
相关表型其次,我们将进行蛋白质相互作用筛选,以确定新的蛋白质
可能与细胞质PER和TIM相互作用。这项研究的结果将使我们
重要的见解的非昼夜表达的时钟蛋白的功能意义。
有越来越多的证据表明,基因被认为是专门作为时钟组件
具有其他重要的多效性作用。它们以非昼夜节律的方式在苍蝇和哺乳动物中起作用。
因此,了解生物钟基因在模式生物中的非昼夜节律功能,
为与人类健康相关的类似过程提供有价值的见解。
项目成果
期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Yolk protein is expressed in the insect testis and interacts with sperm.
- DOI:10.1186/1471-213x-8-64
- 发表时间:2008-06-13
- 期刊:
- 影响因子:0
- 作者:Bebas P;Kotwica J;Joachimiak E;Giebultowicz JM
- 通讯作者:Giebultowicz JM
Circadian regulation of response to oxidative stress in Drosophila melanogaster.
- DOI:10.1016/j.bbrc.2008.07.011
- 发表时间:2008-09-19
- 期刊:
- 影响因子:3.1
- 作者:Krishnan, Natraj;Davis, Andrew J.;Giebultowicz, Jadwiga M.
- 通讯作者:Giebultowicz, Jadwiga M.
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Jadwiga M Giebultowicz其他文献
Jadwiga M Giebultowicz的其他文献
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{{ truncateString('Jadwiga M Giebultowicz', 18)}}的其他基金
Circadian regulation of neuroprotective genes during aging
衰老过程中神经保护基因的昼夜节律调节
- 批准号:
9111180 - 财政年份:2016
- 资助金额:
$ 7.86万 - 项目类别:
Role of circadian clocks in maintaining a healthy nervous system
生物钟在维持神经系统健康中的作用
- 批准号:
8458655 - 财政年份:2011
- 资助金额:
$ 7.86万 - 项目类别:
Exploring links between circadian clocks and aging.
探索生物钟与衰老之间的联系。
- 批准号:
8225201 - 财政年份:2011
- 资助金额:
$ 7.86万 - 项目类别:
Exploring links between circadian clocks and aging.
探索生物钟与衰老之间的联系。
- 批准号:
8030253 - 财政年份:2011
- 资助金额:
$ 7.86万 - 项目类别:
Role of circadian clocks in maintaining a healthy nervous system
生物钟在维持神经系统健康中的作用
- 批准号:
8288704 - 财政年份:2011
- 资助金额:
$ 7.86万 - 项目类别:
Role of circadian clocks in maintaining a healthy nervous system
生物钟在维持神经系统健康中的作用
- 批准号:
8176952 - 财政年份:2011
- 资助金额:
$ 7.86万 - 项目类别:
Exploring links between circadian clocks and aging.
探索生物钟与衰老之间的联系。
- 批准号:
8265501 - 财政年份:2011
- 资助金额:
$ 7.86万 - 项目类别:
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