Genetic analysis of iron homeostasis in C. elegans
线虫铁稳态的遗传分析
基本信息
- 批准号:7891084
- 负责人:
- 金额:$ 10.49万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-05-17 至 2010-08-31
- 项目状态:已结题
- 来源:
- 关键词:AffinityAnimal ModelAnimalsBe++ elementBerylliumBindingBinding SitesBiochemicalBiological ProcessCaenorhabditis elegansCellsChelating AgentsCitric Acid CycleConserved SequenceDataElementsEnhancersEukaryotic CellFerritinFluorescenceFree RadicalsGene ExpressionGene Expression ProfilingGenesGeneticGenetic ScreeningGenetic TranscriptionGoalsGreen Fluorescent ProteinsHemeHomeostasisHomologous GeneHybridsIronIron-Regulatory ProteinsLearningMediatingMutateMutationOrganOrganismPhotosynthesisProteinsRegulationRegulatory ElementReporterRespirationRoleSignal PathwaySignal TransductionSystemTissuesTranscriptional RegulationTransferrin ReceptorTransgenesYeastsbaseexpectationgenetic analysisinterestmacromoleculemetabolic abnormality assessmentmutantnoveloxygen transportplant fungipromoterprotein expressiontranscription factoruptake
项目摘要
DESCRIPTION (provided by applicant): Iron has an essential role in many biological processes, including DMA synthesis/respiration, the tricarboxylic acid cycle, oxygen transport, heme synthesis and photosynthesis. But iron can also be toxic due to its ability to generate free radicals that damage macromolecules in cells. Consequently, organisms have evolved precise mechanisms to sense, acquire and store iron. Our goal is to learn more about how eukaryotic cells sense iron, generate a signal and transduce the signal into regulating iron homeostasis. Specifically, we are interested in understanding how transcription factors sense iron, and regulate gene expression in animal cells. While iron-mediated transcription factors have been identified in fungi and plants, little is known about the mechanisms and the proteins regulating iron-mediated transcriptional regulation in animal cells. We have discovered that Caenorhabditis elegans express ferritin (CeFTN-1 and CeFTN-2), which are key iron storage proteins. Our data shows that Ceftn-1 and Ceftn-2 are transcriptionally regulated by iron, and that cis-regulatory sequences present in their 5' upstream regions are required for this regulation. We propose to identify the cis-regulatory sequences and the iron-sensing transcription factor that binds these elements, and to determine how this transcription factor senses iron. We will also identify other C. elegans genes involved in iron signaling pathways. C. elegans offers a complementary approach to iron metabolic studies in other organisms, in that they are amenable to genetic analysis, they have organ/tissue systems, and they have homologs of genes encoding proteins involved in mammalian iron homeostasis. The specific aims are 1) to characterize cis-acting iron-regulatory elements in Ceftn-1 and Ceftn-2 promoters, 2) to purify the C. elegans transcription factor that regulates the Ceftn-1 and Ceftn-2 genes, and to determine how this factor controls ferritin expression, and 3) to identify genes involved in iron signaling pathways in C. elegans using a green fluorescence protein (GFP)-based screen.
描述(由申请人提供):铁在许多生物过程中具有重要作用,包括 DMA 合成/呼吸、三羧酸循环、氧运输、血红素合成和光合作用。但铁也可能有毒,因为它能够产生自由基,破坏细胞中的大分子。因此,生物体进化出了精确的机制来感知、获取和储存铁。我们的目标是更多地了解真核细胞如何感知铁、产生信号并将信号转导来调节铁稳态。具体来说,我们有兴趣了解转录因子如何感知铁并调节动物细胞中的基因表达。虽然铁介导的转录因子已在真菌和植物中被发现,但对于动物细胞中铁介导的转录调控的机制和蛋白质知之甚少。我们发现秀丽隐杆线虫表达铁蛋白(CeFTN-1 和 CeFTN-2),这是关键的铁储存蛋白。我们的数据显示 Ceftn-1 和 Ceftn-2 受铁转录调节,并且存在于其 5' 上游区域的顺式调节序列是这种调节所必需的。我们建议鉴定顺式调控序列和结合这些元件的铁感应转录因子,并确定该转录因子如何感应铁。我们还将鉴定参与铁信号通路的其他秀丽隐杆线虫基因。线虫为其他生物体中的铁代谢研究提供了一种补充方法,因为它们适合遗传分析,它们具有器官/组织系统,并且它们具有编码参与哺乳动物铁稳态的蛋白质的基因的同源物。具体目标是 1) 表征 Ceftn-1 和 Ceftn-2 启动子中的顺式作用铁调节元件,2) 纯化调节 Ceftn-1 和 Ceftn-2 基因的线虫转录因子,并确定该因子如何控制铁蛋白表达,3) 使用基于绿色荧光蛋白 (GFP) 的筛选来识别秀丽隐杆线虫中涉及铁信号通路的基因。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Elizabeth Ann Leibold其他文献
Elizabeth Ann Leibold的其他文献
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Cell Cycle Regulation of IRP2 Phosphorylation During Hematopoiesis
造血过程中 IRP2 磷酸化的细胞周期调控
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$ 10.49万 - 项目类别:
Genetic analysis of iron homeostasis in C. elegans
线虫铁稳态的遗传分析
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7414595 - 财政年份:2006
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Genetic analysis of iron homeostasis in C. elegans
线虫铁稳态的遗传分析
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7224958 - 财政年份:2006
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Genetic Analysis of Iron Homeostasis in C. elegans
线虫铁稳态的遗传分析
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