Illuminating cell hollowing; the mysterious process of seamless tube formation
照亮细胞空洞;
基本信息
- 批准号:8085850
- 负责人:
- 金额:$ 5.13万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-05-01 至 2012-04-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAnimalsBiologicalBiological ModelsBlood VesselsBlood capillariesCancerousCell membraneCell modelCell physiologyCellsChimeric ProteinsCytoskeletonDataDefectDrosophila genusEndocytic VesicleEndothelial CellsEpithelialEventExhibitsGenerationsGenesGenetic ScreeningGrowthGrowth FactorGrowth and Development functionHumanHypoxiaImaging TechniquesImmuneImmunohistochemistryJurkat CellsKnowledgeLifeMediatingMembraneMembrane Protein TrafficMicroscopyMicrotubulesModelingMolecularMolecular GeneticsMutationNutrientOrthologous GeneOxygenPathway interactionsPlayProcessProteinsPublic HealthRoleRouteSecretory VesiclesSeriesShapesSiteSynapsesSystemTechniquesTimeTracheaTransgenic OrganismsTubeTumor AngiogenesisVacuoleVascular Endothelial Growth FactorsVesicleWaste ProductsWorkWound Healingangiogenesisapical membraneblindbody systemcapillarycellular imagingflyin vivoinsightmutantneoplastic cellneovascularizationneuronal cell bodynew growthpositional cloningtherapeutic targettraffickingtumortumorigenesisvesicle/vacuole
项目摘要
DESCRIPTION (provided by applicant): Cancerous cells release growth factors such as VEGF to induce growth of new blood vessels in their microenvironment. Neovascularization provides oxygen and nutrients to the growing tumor, while removing any waste products and providing an efficient route for the spread of tumor cells to other organ systems. In the absence of angiogenesis, tumors cannot develop more than 3-4 mm in size; hence, angiogenesis has become a therapeutic target. The vertebrate vasculature and Drosophila tracheal system share similar mechanisms of branch sprouting and tube formation, and therefore the tractable Drosophila model system will provide much needed insight into capillary lumenization during angiogenesis. Ultrastructural studies have shown that branch connection points are frequently comprised of "seamless" tubes. Seamless tubes are unicellular tubes that appear doughnut like in cross-section. Endothelial cells in culture form seamless tubes by the fusion of intracellular vacuoles before eventually connecting with other endothelial cells to generate larger tubes with intercellular seams. These observations have led to a "cell hollowing" model of seamless tube formation in which membrane vesicles or vacuoles are targeted to the center of the cell, where they coalesce and fuse to generate an internal apical membrane. This proposal seeks to define the genetic, molecular, and cell biological mechanisms that underlie formation of seamless tubes, taking a two-pronged approach to address this question in the Drosophila tracheal system. First, the process of seamless tube formation will be elucidated by studying mutants identified in a forward genetic screen that exhibit defects in seamless tubes. The second prong of the approach entails live cell imaging studies in which well-characterized and fluorescently-tagged membrane trafficking components are utilized to visualize seamless tube formation in vivo in real time.
DIRECT RELEVANCE TO PUBLIC HEALTH: The induction of new blood vessels Is critical for many aspects of growth and development, but particularly important during wound healing and tumorigenesis. This proposal aims to describe the mechanism by which a cell can transform into a tube (such as a blood vessel) using the Drosophila trachea as a model system.
描述(申请人提供):癌细胞释放生长因子,如血管内皮生长因子,在其微环境中诱导新血管的生长。新生血管为生长中的肿瘤提供氧气和营养,同时清除任何废物,并为肿瘤细胞扩散到其他器官系统提供有效途径。在没有血管生成的情况下,肿瘤的大小不能超过3-4毫米;因此,血管生成已成为治疗的靶点。脊椎动物的血管系统和果蝇的气管系统具有相似的分支萌发和管状形成的机制,因此,易驯化的果蝇模型系统将为血管生成过程中的毛细血管管腔形成提供迫切需要的见解。超微结构研究表明,支管连接点常常由“无缝”管组成。无缝管是横截面上看起来像甜甜圈的单细胞管。培养中的内皮细胞通过融合细胞内的空泡形成无缝管,然后最终与其他内皮细胞连接,生成具有细胞间接缝的更大的管。这些观察结果导致了一种无缝管形成的“细胞空心化”模型,在这种模型中,膜泡或液泡被定位到细胞的中心,在那里它们聚集并融合,形成内部的顶膜。这项建议试图定义形成无缝管的遗传、分子和细胞生物学机制,采取双管齐下的方法来解决果蝇气管系统中的这个问题。首先,无缝管的形成过程将通过研究在正向遗传筛查中发现的显示无缝管缺陷的突变来阐明。该方法的第二个方面需要进行活细胞成像研究,在该研究中,充分表征和荧光标记的膜运输组件被用于实时可视化体内无缝管的形成。
与公众健康直接相关:新血管的诱导对于生长和发育的许多方面都是关键的,但在伤口愈合和肿瘤形成过程中尤其重要。这项建议旨在以果蝇气管为模型系统,描述细胞转化为管状(如血管)的机制。
项目成果
期刊论文数量(0)
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Jodi Schottenfeld其他文献
Jodi Schottenfeld的其他文献
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{{ truncateString('Jodi Schottenfeld', 18)}}的其他基金
Illuminating cell hollowing; the mysterious process of seamless tube formation
照亮细胞空洞;
- 批准号:
7806157 - 财政年份:2010
- 资助金额:
$ 5.13万 - 项目类别:
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