Mitochondrial genes and TOR signaling in Drosophila
果蝇线粒体基因和 TOR 信号传导
基本信息
- 批准号:9280618
- 负责人:
- 金额:$ 4.4万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-06-01 至 2019-03-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAgingAutophagocytosisBindingCell physiologyCellsCommunicationComplexCuesDiseaseDrosophila genusDrosophila melanogasterDrug usageEnergy MetabolismExposure toFastingFunctional disorderGene ExpressionGenesGenetic TranscriptionGenomicsGenotypeHumanHypertrophyKnowledgeLaboratoriesLongevityMediatingMetabolicMetabolic DiseasesMetabolismMitochondriaMitochondrial DNAMolecular GeneticsMutationNuclearNutrientPathway interactionsPharmaceutical PreparationsPhenotypePhosphorylationPhosphotransferasesPlayProcessProductionProteomicsRNA InterferenceRegulationRoleSignal PathwaySignal TransductionSirolimusSystemTestingVariantWorkdesigndifferential expressiondrug sensitivityexperimental studyfeedinggene productgenetic variantinhibitor/antagonistinsightmitochondrial genomemitochondrial metabolismnovelnovel strategiesprotein expressionpublic health relevancerespiratoryresponsesensortherapeutic target
项目摘要
DESCRIPTION (provided by applicant): At the cellular level metabolic function is regulated by TOR kinase. TOR acts as a sensor of the cellular metabolic state and appropriately regulates metabolically-sensitive cellular processes including mitochondrial function. However, the mechanism connecting TOR to mitochondria is currently unknown. Previous work in the Rand laboratory revealed the TOR inhibitory drug rapamycin elicits different mitochondrial responses in Drosophila strains that are genetically identical except for their mitochondrial genomes. I will
use genomics and proteomics as well as focused studies on known components of the TOR signaling pathway to elucidate the network of factors that mediate the rapamycin response in this system. This novel approach of using mitochondrial genome variants will provide insight into the regulation of mitochondrial function by TOR signaling and the role of the mitochondrial genome in metabolic signaling. My work has potential to reveal therapeutic targets for metabolic dysfunction in disease and shortened lifespan.
描述(由申请人提供):在细胞水平,代谢功能由TOR激酶调节。TOR充当细胞代谢状态的传感器,并适当地调节代谢敏感的细胞过程,包括线粒体功能。然而,连接TOR与线粒体的机制目前尚不清楚。兰德实验室先前的工作揭示了TOR抑制药物雷帕霉素在果蝇品系中引起不同的线粒体反应,这些果蝇品系除了线粒体基因组之外在遗传上是相同的。我会
使用基因组学和蛋白质组学以及对TOR信号通路已知组分的集中研究来阐明介导该系统中雷帕霉素反应的因子网络。这种使用线粒体基因组变体的新方法将通过TOR信号传导和线粒体基因组在代谢信号传导中的作用来深入了解线粒体功能。我的工作有可能揭示疾病中代谢功能障碍和缩短寿命的治疗目标。
项目成果
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