The Cytoskeletal Stress Response: A Novel Facet to Protecting Cell Integrity during Aging
细胞骨架应激反应:衰老过程中保护细胞完整性的一个新方面
基本信息
- 批准号:9190230
- 负责人:
- 金额:$ 5.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-07-01 至 2019-06-30
- 项目状态:已结题
- 来源:
- 关键词:ActinsAddressAdultAffectAgeAgingAging-Related ProcessAnimal ModelAnimalsApplications GrantsArchitectureAttentionAutophagocytosisAxonal TransportBiochemicalCaenorhabditis elegansCell physiologyCellsCellular Stress ResponseCessation of lifeChargeClinicalCobaltCytoskeletal ModelingCytoskeletonDataDefectDiseaseDisease modelElderlyEndocytosisEndoplasmic ReticulumExocytosisF-ActinFailureFiberGenesGoalsHealthHeat-Shock ResponseHomeostasisImageImmunofluorescence ImmunologicLibrariesLinkLongevityMaintenanceMammalsMapsMeasuresMediatingMessenger RNAMethodsMitochondriaModelingMolecularMolecular ChaperonesMolecular ProfilingMovementMuscleMuscle CellsMuscle FibersMyopathyNatureNerve DegenerationOrganellesOrganismPathway interactionsPlayPremature aging syndromeProteinsRegulationResearchRoleSaccharomyces cerevisiaeStagingStaining methodStainsStressSupporting CellSystemT-LymphocyteTestingTherapeutic InterventionTissuesVesicleWorkYeastsabstractingage relatedagedbiological adaptation to stresscell typecellular imagingfunctional declineheat shock transcription factorimaging modalityinterestknock-downlive cell imagingloss of functionmitochondrial fitnessmutantnovelnovel strategiesoverexpressionpreventrecombinaseresponsescreeningtranscription factor
项目摘要
Project Summary/Abstract
This grant proposal seeks to identify the first known cytoskeleton-specific stress response and the
potential regulators of this pathway. Previous work in yeast has identified an age-associated decline in
cytoskeletal function and its implications in lifespan, while recent work in C. elegans have identified HSF-1 in
mediating a protective role in cytoskeletal integrity. Marrying these findings, we propose to characterize both
systemic and tissue-specific cytoskeletal decline as a function of age in the multicellular model organism, C.
elegans. Next, we would like to identify the key players working both in synergy or independently of HSF-1 in
protecting cytoskeletal integrity under stress and aging. Finally, we can determine whether the cytoskeletal
stress response itself declines over age, as many stress response pathways do – including mitochondrial,
endoplasmic reticulum, and cytoplasmic – and whether ectopic activation can rescue cytoskeletal function in
advanced age.
We will employ both biochemical and imaging methods to test our hypotheses. We propose to study
cytoskeletal function by imaging of actin using LifeAct. In addition, we will purify actin proteins in a tissue-
specific manner and study their function in worms at various stages of adulthood. Finally, we propose to
perform a candidate screen of 400 transcription factors to identify novel regulators of cytoskeletal function.
Here, endocytosis and organization of muscle fibers will be used as a readout for cytoskeletal integrity and
function. At the culmination of this study, we will have characterized the cytoskeletal stress response as a
function of age. Moving forward, this will open exciting avenues of research in continuing to map out the
mechanistic pathway of the cytoskeletal stress response, as well as identifying the conservation of this
mechanism in mammals and disease models.
项目总结/文摘
项目成果
期刊论文数量(0)
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Ryo Higuchi-Sanabria其他文献
Ryo Higuchi-Sanabria的其他文献
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{{ truncateString('Ryo Higuchi-Sanabria', 18)}}的其他基金
More than just a load control: cytoskeletal form and function during aging
不仅仅是负荷控制:衰老过程中的细胞骨架形式和功能
- 批准号:
10476624 - 财政年份:2020
- 资助金额:
$ 5.25万 - 项目类别:
More than just a load control: cytoskeletal form and function during aging
不仅仅是负荷控制:衰老过程中的细胞骨架形式和功能
- 批准号:
10622612 - 财政年份:2020
- 资助金额:
$ 5.25万 - 项目类别:
More than just a load control: cytoskeletal form and function during aging
不仅仅是负荷控制:衰老过程中的细胞骨架形式和功能
- 批准号:
10469736 - 财政年份:2020
- 资助金额:
$ 5.25万 - 项目类别:
The Cytoskeletal Stress Response: A Novel Facet to Protecting Cell Integrity during Aging
细胞骨架应激反应:衰老过程中保护细胞完整性的一个新方面
- 批准号:
9302226 - 财政年份:2016
- 资助金额:
$ 5.25万 - 项目类别:
The Cytoskeletal Stress Response: A Novel Facet to Protecting Cell Integrity during Aging
细胞骨架应激反应:衰老过程中保护细胞完整性的一个新方面
- 批准号:
9474556 - 财政年份:2016
- 资助金额:
$ 5.25万 - 项目类别:
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