LIVE IMAGING OF BONE REGENERATION IN ZEBRAFISH
斑马鱼骨再生的实时成像
基本信息
- 批准号:10549315
- 负责人:
- 金额:$ 52.04万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-02-01 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:AdultAgeAmericanAutomobile DrivingBehaviorBiographyBiosensorBone DiseasesBone MatrixBone RegenerationCell ProliferationCell divisionCellsCessation of lifeChemicalsClinicalCompetenceComplementComplexComputer AnalysisCytoskeletonData SetDaughterDermalEmbryoEpithelial CellsEventExtracellular Signal Regulated KinasesFGF12 geneFractureGene ExpressionGenesGeneticGenetic TranscriptionGoalsGrowthGrowth FactorHeterogeneityHypertrophyImageIndividualInjuryJawLabelLaboratoriesLifeLigandsLimb structureLinkMapsMediatingMessenger RNAMethodologyMethodsMitogensModelingMolecularMolecular GeneticsMonitorMorphogenesisNatural regenerationOsteoblastsOsteoclastsPathway interactionsPatternPopulationPrimordiumProcessProliferatingProtein AnalysisPublishingRegenerative capacityRegulationRiskSignal TransductionSkeletal boneSkinStructureSystemTestingTissuesTransgenic OrganismsTraumaTravelWorkZebrafishbonebone imagingcell behaviorcraniofacial developmenteconomic impactexperimental studygenetic approachimaging modalityimaging platformimprovedin vivo imaginginsightlimb amputationlive cell imagingmathematical modelmembermigrationnovelpharmacologicprogramsregeneration potentialregenerative growthresponsesingle cell sequencingsocioeconomicsspatiotemporaltranscription factortranscriptometranscriptomic profilingtransmission process
项目摘要
Abstract
Mammalian bone has the capacity throughout life to regenerate in response to fracture injury. However, there
is a ceiling for this regenerative potential, with hurdles to regeneration after a major trauma like limb
amputation. This has a significant socioeconomic impact, as it is estimated that at least one in two Americans
over age 50 is expected to have or be at risk of bone disease, and every year an estimated 1.5 million
individuals suffer a fracture due to bone disease. Recently, we have developed imaging methods to study how
osteoblasts drive bone regeneration in zebrafish, which display robust regeneration after major injury to bony
structures like their fins, scales, and jaws. Our goal is to exploit this regenerative capacity, new imaging
platforms we have created, and the molecular genetic approaches available in zebrafish to improve our ability
to understand and manipulate the regenerative capacity of bone. The goal of this proposal is to generate an in
toto map of the cellular and signaling events that regenerate patterned skeletal bone. Our experiments will test
the hypothesis that correct patterning of regenerating bone requires dynamic signaling events that control
osteoblast behaviors at individual and population levels. 1) We will use long-term live imaging, labeling with
photo-convertible proteins, and computational analysis to generate a detailed map of how cell proliferation,
hypertrophy and cellular flows, and interactions with neighboring tissues drive bone regeneration. 2) We will
use cutting edge biosensors, live imaging, computational approaches, and mathematical modeling to dissect
how traveling waves of chemical signals stimulate the growth of a regenerating osteoblast population. 3) We
will use transcriptome profiling approaches to derive further insights on the dynamics of growth factor signaling,
including single-cell sequencing-based approaches to link gene expression programs with osteoblast
behaviors. These experiments will define a novel quantitative framework for understanding how osteoblast
behaviors orchestrate bone regeneration.
抽象的
哺乳动物的骨骼在骨折损伤的一生中具有再生能力。但是,那里
是这种再生潜力的上限
截肢。这具有重大的社会经济影响,据估计,至少有二分之一的美国人
预计50岁以上将有或有骨病的风险,每年估计有150万
个体因骨骼疾病而导致骨折。最近,我们开发了成像方法来研究
成骨细胞驱动斑马鱼中的骨骼再生,斑马鱼在重大受伤后表现出强大的再生
像鳍,鳞片和下巴这样的结构。我们的目标是利用这种再生能力,新成像
我们创建的平台以及斑马鱼中可用的分子遗传方法,以提高我们的能力
了解和操纵骨骼的再生能力。该提议的目的是生成一个
再生图案骨骼骨的细胞和信号事件的toto图。我们的实验将测试
纠正再生骨的校正模式需要动态信号事件的假说
成骨细胞的个人和人口水平的行为。 1)我们将使用长期的实时成像,与
光转换蛋白和计算分析,以生成细胞增殖的详细图表,
肥大和细胞流,以及与邻近组织的相互作用驱动骨骼再生。 2)我们会的
使用尖端生物传感器,实时成像,计算方法和数学建模
化学信号的行进波如何刺激再生成骨细胞种群的生长。 3)我们
将使用转录组分析方法来获得对生长因子信号传导动力学的进一步见解,
包括基于单细胞测序的方法,将基因表达程序与成骨细胞联系起来
行为。这些实验将定义一个新颖的定量框架,以了解成骨细胞如何
行为协调骨骼再生。
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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Stefano Di Talia其他文献
Stefano Di Talia的其他文献
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{{ truncateString('Stefano Di Talia', 18)}}的其他基金
Mechanisms and developmental functions of cytoplasmic flows in early embryogenesis
早期胚胎发生中细胞质流动的机制和发育功能
- 批准号:
10297436 - 财政年份:2021
- 资助金额:
$ 52.04万 - 项目类别:
Mechanisms and developmental functions of cytoplasmic flows in early embryogenesis
早期胚胎发生中细胞质流动的机制和发育功能
- 批准号:
10796050 - 财政年份:2021
- 资助金额:
$ 52.04万 - 项目类别:
Mechanisms and developmental functions of cytoplasmic flows in early embryogenesis
早期胚胎发生中细胞质流动的机制和发育功能
- 批准号:
10491186 - 财政年份:2021
- 资助金额:
$ 52.04万 - 项目类别:
Time-keeping mechanisms of embryonic cell cycles
胚胎细胞周期的计时机制
- 批准号:
10603282 - 财政年份:2017
- 资助金额:
$ 52.04万 - 项目类别:
Time-keeping Mechanisms in Drosophila Embryonic Development
果蝇胚胎发育的计时机制
- 批准号:
8839511 - 财政年份:2014
- 资助金额:
$ 52.04万 - 项目类别:
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