A Holistic Approach to Understanding Small Heat Shock Protein Mechanism
了解小热激蛋白机制的整体方法
基本信息
- 批准号:10611681
- 负责人:
- 金额:$ 8.24万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-05-01 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:Age related macular degenerationAgingBlindnessBrain Hypoxia-IschemiaCataractCell AgingCellsChronic stressComprehensionCorneaCrystalline LensDeuteriumDevelopmentDiabetic RetinopathyDiseaseExposure toFailureGoalsGrainHealthHeat shock proteinsHydrogenInjuryLeadLinkMaintenanceMass Spectrum AnalysisModelingModificationMolecular ChaperonesMutationNeurodegenerative DisordersOcular PathologyPathologyPhysiologicalProteinsResolutionRetinaSmokingStressStructureTechniquesTissuesUltraviolet Rayscrosslinkfirst responderholistic approachlenslens transparencynovelprotein aggregationprotein misfoldingresponse
项目摘要
ABSTRACT/SUMMARY
Cells have numerous strategies to cope with the consequences of stresses that cause protein
misfolding and aggregation and lead to formation of plaques, fibrils, and other aggregated
species encountered in aging cells, cataract, and neurodegenerative diseases. The protein
chaperones known as small heat shock proteins are the cell’s first responders and are therefore
key to maintenance of cellular health. Ocular tissues are subjected to stresses such as
exposure to UV light, smoking, hypoxia, and ischemia. sHSP function is linked to three of the
most prevalent ocular pathologies leading to blindness worldwide: cataract, age-related macular
degeneration, and diabetic retinopathy which together account for 65% of world blindness. In
lens, sHSPs perform the critical task of maintaining lens transparency and failure to do so is
directly linked to cataract. sHSPs are expressed constitutively in retinal cells and are
upregulated following injury or stress. Mechanisms used by sHSPs to delay the onset of
aggregation of proteins remain enigmatic due to technical challenges posed by sHSPs and the
aggregate-prone proteins they protect. Recent developments in the study of disordered proteins
and breakthroughs made during the previous period of this long-standing project promise to
overcome this critical barrier to mechanistic understanding. Techniques such as NMR,
hydrogen-deuterium exchange/mass spectrometry, and covalent cross-linking/mass
spectrometry can provide fine-grained information regarding disordered regions of sHSPs that
have largely gone uncharacterized but are known to be essential for sHSP activity. The goal of
this renewal application is to develop a holistic (“characterized by comprehension of the parts of
something as intimately interconnected and explicable only by reference to the whole”)
understanding of sHSP structure and function. The effects of stress conditions, modifications,
and mutations will be assessed and interpreted in the context of the resultant novel models.
摘要/摘要
细胞有许多策略来应对导致蛋白质的压力的后果。
错误折叠和聚集,并导致斑块、纤维和其他聚集的形成
在衰老细胞、白内障和神经退行性疾病中遇到的物种。这种蛋白质
被称为小热休克蛋白的伴侣蛋白是细胞的第一反应者,因此
维持细胞健康的关键。眼组织会受到压力,如
暴露在紫外线下,吸烟,缺氧和缺血。SHSP函数链接到三个
全球最常见的致盲眼病:白内障、老年性黄斑
变性和糖尿病视网膜病变加起来占世界失明的65%。在……里面
透镜,sHSP执行维持透镜透明度的关键任务,而未能做到这一点是
与白内障有直接联系。SHSPs在视网膜细胞中有结构性表达,并且
在受伤或压力后表达上调。热休克蛋白用来延迟发病的机制
蛋白质的聚集仍然是个谜,因为sHSP和
它们保护的易于聚集的蛋白质。无序蛋白质研究的新进展
以及在这一长期项目的前一段时间取得的突破承诺
克服这一机械理解的关键障碍。核磁共振等技术
氢-氚交换/质谱学和共价交联/质量法
光谱分析可以提供关于sHSPs无序区域的细粒度信息
在很大程度上没有确定其特征,但已知对SHSP活动是必不可少的。的目标是
这个续订申请是为了开发一个整体的(特征是理解的部分
只有通过参照整体才能紧密联系和解释的东西“)
了解SHSP的结构和功能。压力条件的影响,修改,
突变将在所产生的新模型的背景下进行评估和解释。
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 }}
Rachel E Klevit其他文献
Rachel E Klevit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('Rachel E Klevit', 18)}}的其他基金
Expanding Mechanistic Insights into Protein Ubiquitylation
扩展对蛋白质泛素化的机制见解
- 批准号:
10796652 - 财政年份:2022
- 资助金额:
$ 8.24万 - 项目类别:
Allosteric adhesins of enterobacterial pathogens
肠杆菌病原体的变构粘附素
- 批准号:
10512013 - 财政年份:2022
- 资助金额:
$ 8.24万 - 项目类别:
Expanding Mechanistic Insights into Protein Ubiquitylation
扩展对蛋白质泛素化的机制见解
- 批准号:
10330645 - 财政年份:2022
- 资助金额:
$ 8.24万 - 项目类别:
Expanding Mechanistic Insights into Protein Ubiquitylation
扩展对蛋白质泛素化的机制见解
- 批准号:
10676084 - 财政年份:2022
- 资助金额:
$ 8.24万 - 项目类别:
Allosteric adhesins of enterobacterial pathogens
肠杆菌病原体的变构粘附素
- 批准号:
10626963 - 财政年份:2022
- 资助金额:
$ 8.24万 - 项目类别:
Acquisition of Analytical Ultracentrifuge at UW
华盛顿大学购买分析超速离心机
- 批准号:
7790426 - 财政年份:2010
- 资助金额:
$ 8.24万 - 项目类别:
Structural and Functional Characterization of BRCA1/BARD1
BRCA1/BARD1 的结构和功能表征
- 批准号:
7931268 - 财政年份:2009
- 资助金额:
$ 8.24万 - 项目类别:
Structure/Function Studies of Small Heat Shock Proteins
小热激蛋白的结构/功能研究
- 批准号:
7415008 - 财政年份:2007
- 资助金额:
$ 8.24万 - 项目类别:
Structure/Function Studies of Small Heat Shock Proteins
小热激蛋白的结构/功能研究
- 批准号:
8437511 - 财政年份:2007
- 资助金额:
$ 8.24万 - 项目类别:
相似海外基金
Interplay between Aging and Tubulin Posttranslational Modifications
衰老与微管蛋白翻译后修饰之间的相互作用
- 批准号:
24K18114 - 财政年份:2024
- 资助金额:
$ 8.24万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
The Canadian Brain Health and Cognitive Impairment in Aging Knowledge Mobilization Hub: Sharing Stories of Research
加拿大大脑健康和老龄化认知障碍知识动员中心:分享研究故事
- 批准号:
498288 - 财政年份:2024
- 资助金额:
$ 8.24万 - 项目类别:
Operating Grants
EMNANDI: Advanced Characterisation and Aging of Compostable Bioplastics for Automotive Applications
EMNANDI:汽车应用可堆肥生物塑料的高级表征和老化
- 批准号:
10089306 - 财政年份:2024
- 资助金额:
$ 8.24万 - 项目类别:
Collaborative R&D
Baycrest Academy for Research and Education Summer Program in Aging (SPA): Strengthening research competencies, cultivating empathy, building interprofessional networks and skills, and fostering innovation among the next generation of healthcare workers t
Baycrest Academy for Research and Education Summer Program in Aging (SPA):加强研究能力,培养同理心,建立跨专业网络和技能,并促进下一代医疗保健工作者的创新
- 批准号:
498310 - 财政年份:2024
- 资助金额:
$ 8.24万 - 项目类别:
Operating Grants
関節リウマチ患者のSuccessful Agingに向けたフレイル予防対策の構築
类风湿性关节炎患者成功老龄化的衰弱预防措施的建立
- 批准号:
23K20339 - 财政年份:2024
- 资助金额:
$ 8.24万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Life course pathways in healthy aging and wellbeing
健康老龄化和福祉的生命历程路径
- 批准号:
2740736 - 财政年份:2024
- 资助金额:
$ 8.24万 - 项目类别:
Studentship
I-Corps: Aging in Place with Artificial Intelligence-Powered Augmented Reality
I-Corps:利用人工智能驱动的增强现实实现原地老龄化
- 批准号:
2406592 - 财政年份:2024
- 资助金额:
$ 8.24万 - 项目类别:
Standard Grant
NSF PRFB FY 2023: Connecting physiological and cellular aging to individual quality in a long-lived free-living mammal.
NSF PRFB 2023 财年:将生理和细胞衰老与长寿自由生活哺乳动物的个体质量联系起来。
- 批准号:
2305890 - 财政年份:2024
- 资助金额:
$ 8.24万 - 项目类别:
Fellowship Award
虚弱高齢者のSuccessful Agingを支える地域課題分析指標と手法の確立
建立区域问题分析指标和方法,支持体弱老年人成功老龄化
- 批准号:
23K20355 - 财政年份:2024
- 资助金额:
$ 8.24万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
「ケア期間」に着目したbiological aging指標の開発
开发聚焦“护理期”的生物衰老指数
- 批准号:
23K24782 - 财政年份:2024
- 资助金额:
$ 8.24万 - 项目类别:
Grant-in-Aid for Scientific Research (B)