Characterization of Tagged Type IV Collagen
标记的 IV 型胶原蛋白的表征
基本信息
- 批准号:10724541
- 负责人:
- 金额:$ 44.41万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-06-15 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAffinity ChromatographyAllelesAlzheimer&aposs DiseaseAmino AcidsAstrocytesBasement membraneBiochemicalBiological ProcessBiologyBlood VesselsCellsCerebral small vessel diseaseCerebrovascular DisordersCerebrovascular systemCharacteristicsCircular DichroismCollagenCollagen Type IVCongenital DisordersDefectDementiaDepositionDevelopmentDiseaseElectron MicroscopyEmbryoEndoplasmic ReticulumEventExtracellular MatrixFibroblastsFluorescenceFluorescence MicroscopyGeneticGoalsHeterogeneityHomeostasisHumanHybridsImpaired cognitionImpairmentIn VitroKidneyKnowledgeLabelMediatingMethodsMicroscopyMolecularMouse StrainsMusMuscleMutant Strains MiceMutationOrganOutcomePathogenicityPathologicPathologyPhysiologic pulsePost-Translational Protein ProcessingPropertyProtein IsoformsProteinsReporterResearchResourcesSWI1Signal TransductionSortingSystemTestingTissuesValidationVascular Endothelial CellVisualizationWestern Blottingage relatedbiophysical propertiescell behaviorcell typecerebrovascularcerebrovascular healthcognitive changecrosslinkgenome wide association studygenome-widein vivoinducible Creinnovationinsightmutantnovelpuprecombinasespatiotemporaltooltranscriptomicsvascular cognitive impairment and dementia
项目摘要
PROJECT SUMMARY
Mutations in type IV collagen alpha 1 (COL4A1) and alpha 2 (COL4A2) are an important cause of monogenic
cerebral small vessel disease and are also significantly associated with cerebral small vessel disease hallmarks
in large-scale genome wide association studies underscoring their importance for general cerebrovascular health
in humans. The broad goal of our research is to understand the biological functions COL4A1 and COL4A2 in the
extracellular matrix and determine the mechanisms by which they cause genetic and acquired cerebrovascular
disease and disfunction. The specific purpose of this proposal is to validate a potentially powerful tool that will
enable unveiling of tissue specific and temporal changes in collagen deposition and degradation.
The inability to distinguish cell type specific or temporal changes to the extracellular matrix constitutes a
significant obstacle for understanding a fundamental aspect of tissue biology. To address this barrier, we
developed a mouse line in which COL4A1 is fused with switchable fluorescent proteins for isoform-specific
visualization and biochemical tags for differential affinity purification. This simple but powerful tool will enable
unprecedented characterization of spatial, temporal, biochemical and biophysical parameters of ECM that are
currently impossible to achieve. If the detailed validations outlined in this proposal are successful, we will have
developed a transformative tool that will provide significant insight into a fundamental aspect of tissue biology
and that can be applied to every organ of the body in normal development or in pathological settings.
项目摘要
IV型胶原α 1(COL4A1)和α 2(COL4A2)的突变是单基因
脑小血管疾病,也与脑小血管疾病标志显著相关
在大规模的全基因组关联研究中,
在人类身上。我们研究的广泛目标是了解COL4A1和COL4A2在细胞中的生物学功能。
细胞外基质,并确定其引起遗传性和获得性脑血管疾病的机制
疾病和功能障碍。本提案的具体目的是验证一个潜在的强大工具,
能够揭示胶原沉积和降解的组织特异性和时间变化。
无法区分细胞类型特异性或细胞外基质的时间变化构成了一个重要的因素。
这是理解组织生物学基本方面的一个重大障碍。为了克服这一障碍,我们
开发了一种小鼠系,其中COL4A1与可转换荧光蛋白融合,用于同种型特异性
可视化和生物化学标记用于差异亲和纯化。这个简单但强大的工具将使
ECM的空间、时间、生物化学和生物物理参数的前所未有的表征,
目前不可能实现。如果本提案中概述的详细验证成功,我们将
开发了一种变革性的工具,将为组织生物学的基本方面提供重要的见解
并且可以应用于正常发育或病理环境中的身体的每个器官。
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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Douglas Gould其他文献
Douglas Gould的其他文献
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{{ truncateString('Douglas Gould', 18)}}的其他基金
Gene therapy for disorders of the extracellular matrix
细胞外基质疾病的基因治疗
- 批准号:
10658481 - 财政年份:2023
- 资助金额:
$ 44.41万 - 项目类别:
2023 Collagen Gordon Research Conference and Seminar
2023年胶原蛋白戈登研究会议暨研讨会
- 批准号:
10675849 - 财政年份:2023
- 资助金额:
$ 44.41万 - 项目类别:
Role of the Unfolded Protein Response in Photoreceptor Degeneration
未折叠蛋白反应在光感受器变性中的作用
- 批准号:
10331719 - 财政年份:2018
- 资助金额:
$ 44.41万 - 项目类别:
Role of the Unfolded Protein Response in Photoreceptor Degeneration
未折叠蛋白反应在光感受器变性中的作用
- 批准号:
9927834 - 财政年份:2018
- 资助金额:
$ 44.41万 - 项目类别:
Role of the Unfolded Protein Response in Photoreceptor Degeneration
未折叠蛋白反应在光感受器变性中的作用
- 批准号:
10090604 - 财政年份:2018
- 资助金额:
$ 44.41万 - 项目类别:
Genetic and Mechanistic Study of Cerebral Small Vessel Disease
脑小血管病的遗传学及机制研究
- 批准号:
10213843 - 财政年份:2017
- 资助金额:
$ 44.41万 - 项目类别:
Genetic and Mechanistic Study of Cerebral Small Vessel Disease
脑小血管病的遗传学及机制研究
- 批准号:
9750841 - 财政年份:2017
- 资助金额:
$ 44.41万 - 项目类别:
Genetic and Mechanistic Study of Cerebral Small Vessel Disease
脑小血管病的遗传学及机制研究
- 批准号:
9979964 - 财政年份:2017
- 资助金额:
$ 44.41万 - 项目类别:
Investigating the extracellular matrix in vascular development and maintenance
研究细胞外基质在血管发育和维持中的作用
- 批准号:
8762215 - 财政年份:2014
- 资助金额:
$ 44.41万 - 项目类别:
Investigating the extracellular matrix in vascular development and maintenance
研究细胞外基质在血管发育和维持中的作用
- 批准号:
9087349 - 财政年份:2014
- 资助金额:
$ 44.41万 - 项目类别:
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