Chemical editing of nanoscale proteoglycan architecture and organization to control cellular
化学编辑纳米级蛋白聚糖结构和组织以控制细胞
基本信息
- 批准号:9815714
- 负责人:
- 金额:$ 4.52万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-04-01 至 2021-07-31
- 项目状态:已结题
- 来源:
- 关键词:ArchitectureBindingCarbohydratesCell CompartmentationCell membraneCell surfaceChemicalsComplexCore ProteinDevelopmentEngineeringGlycoconjugatesGlycosaminoglycansGoalsGrowth FactorHuman DevelopmentKnowledgeLeadLengthLinkMapsMembraneMethodsMonitorMusMusculoskeletalNatural regenerationOutcomeProtein EngineeringProteoglycanRegenerative MedicineResearchSignal TransductionSiteSkeletal MuscleSkeletal Muscle Satellite CellsStem cellsStructureTechniquesTo specifycellular developmentembryonic stem cellglycosylationnanoscalepolysulfated glycosaminoglycanprogramsproteoglycan core proteinstem cell differentiation
项目摘要
PROJECT SUMMARY
Cellular development is controlled by cell surface proteoglycans, a class of glycoconjugates that can orchestrate
the binding and release of growth factors to initiate differentiation or prime stem cells towards specific lineages.
Proteoglycans are attractive targets for exerting exogenous control to re-program cellular differentiation, and yet
despite their potential for biomedicine, strategies that harness their regulatory functions are limited. This gap is
caused by the lack of techniques that recognize their chemical and nanoscale complexity. Proteoglycans are
composed of a core protein covalently linked to a highly complex, heterogenous mixture of sulfated
glycosaminoglycan carbohydrates. Furthermore, proteoglycans can be located in distinct compartments of the
cell membrane, and this distribution can lead to different outcomes in differentiation. This application outlines the
development of chemical strategies to mimic and probe the nanoscale architecture and organization of
proteoglycans in cellular development. In two specific aims, we will demonstrate that the techniques developed
through this proposal will enable new chemical strategies to control stem cell differentiation and the regeneration
of skeletal muscles. First, we will develop protein engineering strategies that facilitate the bioorthogonal
conjugation of semi-synthetic glycosaminoglycans to specified sites along the proteoglycan core protein chain,
in order to generate "engineered" cell surface proteoglycans with "pre-mapped" glycosylation sites, as well as
defined glycosaminoglycan compositions and lengths. Second, we will develop chemical methods to direct and
monitor the membrane localization of such "engineered" proteoglycans. Both strategies will be applied in order
to study and to exert control over the differentiation of mouse embryonic stem cells and the activation of skeletal
satellite muscle cells. The long-term goal of this proposal is to offer strategies to alter proteoglycan structure in
order to manipulate cellular differentiation, and to harness this knowledge towards understanding the factors that
regulate canonical human development.
项目摘要
细胞发育受细胞表面蛋白聚糖控制,蛋白聚糖是一类糖复合物,
生长因子的结合和释放以启动分化或使干细胞向特定谱系分化。
蛋白聚糖是施加外源性控制以重新编程细胞分化的有吸引力的靶标,然而,
尽管它们在生物医学方面具有潜力,但利用其调节功能的战略是有限的。这种差距
这是由于缺乏识别其化学和纳米级复杂性的技术。蛋白聚糖
由一个核心蛋白共价连接到一个高度复杂的,异质的硫酸化混合物组成,
糖胺聚糖碳水化合物。此外,蛋白聚糖可以位于细胞的不同隔室中
细胞膜,这种分布会导致不同的分化结果。此应用程序概述了
开发化学策略来模拟和探测纳米结构和组织,
蛋白聚糖在细胞发育中的作用在两个具体目标中,我们将证明所开发的技术
通过这一提议,将使新的化学策略能够控制干细胞的分化和再生,
骨骼肌。首先,我们将开发蛋白质工程战略,促进生物正交
半合成糖胺聚糖与蛋白聚糖核心蛋白链沿着的特定位点的缀合,
为了产生具有“预定位”糖基化位点的“工程化”细胞表面蛋白聚糖,以及
确定的糖胺聚糖组成和长度。第二,我们将发展化学方法,
监测这种“工程化”蛋白聚糖的膜定位。这两种策略将按顺序应用
研究和控制小鼠胚胎干细胞的分化和骨骼肌的活化,
卫星肌细胞这项提案的长期目标是提供改变蛋白聚糖结构的策略,
为了操纵细胞分化,并利用这些知识来了解
规范人类发展。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Mia L Huang其他文献
Mia L Huang的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Mia L Huang', 18)}}的其他基金
Mapping glycan-dependent neurexin interactomes
映射聚糖依赖性神经毒素相互作用组
- 批准号:
10675699 - 财政年份:2022
- 资助金额:
$ 4.52万 - 项目类别:
Mapping glycan-dependent neurexin interactomes
映射聚糖依赖性神经毒素相互作用组
- 批准号:
10426737 - 财政年份:2022
- 资助金额:
$ 4.52万 - 项目类别:
Bridging the Glycome and Proteome with Chemical Biology
用化学生物学连接糖组和蛋白质组
- 批准号:
10577364 - 财政年份:2021
- 资助金额:
$ 4.52万 - 项目类别:
Bridging the Glycome and Proteome with Chemical Biology
用化学生物学连接糖组和蛋白质组
- 批准号:
10271719 - 财政年份:2021
- 资助金额:
$ 4.52万 - 项目类别:
Bridging the Glycome and Proteome with Chemical Biology
用化学生物学连接糖组和蛋白质组
- 批准号:
10798880 - 财政年份:2021
- 资助金额:
$ 4.52万 - 项目类别:
Illuminating Galectin-3 Interactions to Disrupt Hepatic Fibrosis
阐明 Galectin-3 相互作用以破坏肝纤维化
- 批准号:
10416673 - 财政年份:2021
- 资助金额:
$ 4.52万 - 项目类别:
Bridging the Glycome and Proteome with Chemical Biology
用化学生物学连接糖组和蛋白质组
- 批准号:
10415215 - 财政年份:2021
- 资助金额:
$ 4.52万 - 项目类别:
Illuminating Galectin-3 Interactions to Disrupt Hepatic Fibrosis
阐明 Galectin-3 相互作用以破坏肝纤维化
- 批准号:
10592028 - 财政年份:2021
- 资助金额:
$ 4.52万 - 项目类别:
Bridging the Glycome and Proteome with Chemical Biology
用化学生物学连接糖组和蛋白质组
- 批准号:
10609533 - 财政年份:2021
- 资助金额:
$ 4.52万 - 项目类别:
Chemical editing of nanoscale proteoglycan architecture and organization to control cellular
化学编辑纳米级蛋白聚糖结构和组织以控制细胞
- 批准号:
9753314 - 财政年份:2018
- 资助金额:
$ 4.52万 - 项目类别:
相似国自然基金
帽结合蛋白(cap binding protein)调控乙烯信号转导的分子机制
- 批准号:32170319
- 批准年份:2021
- 资助金额:58.00 万元
- 项目类别:面上项目
帽结合蛋白(cap binding protein)调控乙烯信号转导的分子机制
- 批准号:
- 批准年份:2021
- 资助金额:58 万元
- 项目类别:
ID1 (Inhibitor of DNA binding 1) 在口蹄疫病毒感染中作用机制的研究
- 批准号:31672538
- 批准年份:2016
- 资助金额:62.0 万元
- 项目类别:面上项目
番茄EIN3-binding F-box蛋白2超表达诱导单性结实和果实成熟异常的机制研究
- 批准号:31372080
- 批准年份:2013
- 资助金额:80.0 万元
- 项目类别:面上项目
P53 binding protein 1 调控乳腺癌进展转移及化疗敏感性的机制研究
- 批准号:81172529
- 批准年份:2011
- 资助金额:58.0 万元
- 项目类别:面上项目
DBP(Vitamin D Binding Protein)在多发性硬化中的作用和相关机制的蛋白质组学研究
- 批准号:81070952
- 批准年份:2010
- 资助金额:35.0 万元
- 项目类别:面上项目
研究EB1(End-Binding protein 1)的癌基因特性及作用机制
- 批准号:30672361
- 批准年份:2006
- 资助金额:24.0 万元
- 项目类别:面上项目
相似海外基金
Collaborative Research: NSF-BSF: How cell adhesion molecules control neuronal circuit wiring: Binding affinities, binding availability and sub-cellular localization
合作研究:NSF-BSF:细胞粘附分子如何控制神经元电路布线:结合亲和力、结合可用性和亚细胞定位
- 批准号:
2321481 - 财政年份:2024
- 资助金额:
$ 4.52万 - 项目类别:
Continuing Grant
Collaborative Research: NSF-BSF: How cell adhesion molecules control neuronal circuit wiring: Binding affinities, binding availability and sub-cellular localization
合作研究:NSF-BSF:细胞粘附分子如何控制神经元电路布线:结合亲和力、结合可用性和亚细胞定位
- 批准号:
2321480 - 财政年份:2024
- 资助金额:
$ 4.52万 - 项目类别:
Continuing Grant
Alkane transformations through binding to metals
通过与金属结合进行烷烃转化
- 批准号:
DP240103289 - 财政年份:2024
- 资助金额:
$ 4.52万 - 项目类别:
Discovery Projects
NPBactID - Differential binding of peptoid functionalized nanoparticles to bacteria for identifying specific strains
NPBactID - 类肽功能化纳米粒子与细菌的差异结合,用于识别特定菌株
- 批准号:
EP/Y029542/1 - 财政年份:2024
- 资助金额:
$ 4.52万 - 项目类别:
Fellowship
Conformations of musk odorants and their binding to human musk receptors
麝香气味剂的构象及其与人类麝香受体的结合
- 批准号:
EP/X039420/1 - 财政年份:2024
- 资助金额:
$ 4.52万 - 项目类别:
Research Grant
Postdoctoral Fellowship: OPP-PRF: Understanding the Role of Specific Iron-binding Organic Ligands in Governing Iron Biogeochemistry in the Southern Ocean
博士后奖学金:OPP-PRF:了解特定铁结合有机配体在控制南大洋铁生物地球化学中的作用
- 批准号:
2317664 - 财政年份:2024
- 资助金额:
$ 4.52万 - 项目类别:
Standard Grant
I-Corps: Translation Potential of Real-time, Ultrasensitive Electrical Transduction of Biological Binding Events for Pathogen and Disease Detection
I-Corps:生物结合事件的实时、超灵敏电转导在病原体和疾病检测中的转化潜力
- 批准号:
2419915 - 财政年份:2024
- 资助金额:
$ 4.52万 - 项目类别:
Standard Grant
The roles of a universally conserved DNA-and RNA-binding domain in controlling MRSA virulence and antibiotic resistance
普遍保守的 DNA 和 RNA 结合域在控制 MRSA 毒力和抗生素耐药性中的作用
- 批准号:
MR/Y013131/1 - 财政年份:2024
- 资助金额:
$ 4.52万 - 项目类别:
Research Grant
CRII: OAC: Development of a modular framework for the modeling of peptide and protein binding to membranes
CRII:OAC:开发用于模拟肽和蛋白质与膜结合的模块化框架
- 批准号:
2347997 - 财政年份:2024
- 资助金额:
$ 4.52万 - 项目类别:
Standard Grant
How lipid binding proteins shape the activity of nuclear hormone receptors
脂质结合蛋白如何影响核激素受体的活性
- 批准号:
DP240103141 - 财政年份:2024
- 资助金额:
$ 4.52万 - 项目类别:
Discovery Projects