In vivo analysis of mechanotransduction
力转导的体内分析
基本信息
- 批准号:10673986
- 负责人:
- 金额:$ 33.46万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-08-01 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:4D ImagingAddressAsthmaBiochemicalBiologicalBiophysicsBiosensorBlood VesselsCaenorhabditis elegansCalciumCell ShapeCellsCellular biologyCommunicationComputer ModelsContractile SystemContractsCyclic AMP-Dependent Protein KinasesEmbryoEngineeringGTP-Binding Protein alpha SubunitsGTP-Binding Protein alpha Subunits, GsGap JunctionsHeart DiseasesHeterotrimeric GTP-Binding ProteinsHypertensionImageIndividualKnowledgeLifeLinkLungMammary glandMeasuresMechanicsModelingMolecular GeneticsNematodaOocytesPhospholipidsPhysiologic pulseProcessProteomicsRegulationReproducibilityReproductive systemResearchRoleSalivary GlandsSignal TransductionSmooth MuscleStretchingStructureSystemTestingTimeTissuesTranslatingTubeTubular formationUterusWorkautomated image analysiscell typecomputerized toolsfilamingene conservationgene networkgenetic manipulationin vivoin vivo Modelinsightlymphatic vesselmechanical signalmechanotransductionnovelpressurereproductive tractresponserho GTPase-activating proteinspatiotemporal
项目摘要
In vivo analysis of mechanotransduction
Cells in biological tubes must integrate biochemical and mechanical cues in order to expand or
contract in a coordinated manner. Inappropriate responses to changing states underlie
conditions such as heart disease, hypertension and asthma. Despite insights from biophysics
and from cell biology on engineered substrates, many important questions remain regarding
how mechanical information is sensed by cells, translated into biochemical signals, and
integrated to produce a coordinated tissue-level response. For example, how is multicellular
contractility regulated in space and time? How are the induction and propagation of biochemical
signals regulated by mechanical cues? How do different cell types within a tissue coordinate
their actions? To address these questions, we have developed an in vivo model, the C. elegans
spermatheca, which is a tubular tissue in the nematode reproductive system comprised of 24
smooth-muscle-like cells that connect to the uterus via a toroidal valve. The major advantages
of this system are that the cells are naturally stretched and contract as oocytes enter, and are
amenable to quantitative live imaging and targeted genetic manipulation, enabling observation
and manipulation of individual cells in the context of an intact tissue. We have discovered that
oocyte entry induces Ca2+ pulses that sweep across the tissue, culminating in a coordinated
contraction that pushes the fertilized embryo into the uterus. Ca2+ release and contractility in the
spermatheca and valve are coordinated such that while the spermathecal bag contracts, the
valve dilates to allow exit of the fertilized embryo. Well-conserved gene networks regulate these
processes, suggesting broad applicability of our findings to other contractile systems. Here, we
propose a combination of 4D imaging of genetically-encoded biosensors, proteomics, molecular
genetics, and modeling to elucidate the mechanisms which coordinate Ca2+ signaling in
response to stretch. Specifically, we will 1) test the hypothesis that the heterotrimeric G protein,
Gαs, signals through PKA to regulate spermathecal contractility; 2) model the mechanisms by
which stretch triggers calcium release and signal propagation; and 3) determine how valve
contractility is regulated, both autonomously and via communication from the spermathecal bag.
This research will lead to important advances in our understanding of the fundamental
mechanisms by which cells convert mechanical information into biochemical signals, and how
this signaling is integrated to regulate tissue function.
机械传导的体内分析
项目成果
期刊论文数量(18)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Stem Cells: Muscle Cells Enwrap Escaped Germline Stem Cells in C. elegans.
干细胞:肌肉细胞包裹线虫中逃逸的生殖系干细胞。
- DOI:10.1016/j.cub.2019.01.035
- 发表时间:2019
- 期刊:
- 影响因子:0
- 作者:Kelley,CharlotteA;Cram,ErinJ
- 通讯作者:Cram,ErinJ
Tension-dependent RHGF-1 recruitment to stress fibers drives robust spermathecal tissue contraction.
- DOI:10.1083/jcb.202203105
- 发表时间:2023-02-06
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
The DSL ligand APX-1 is required for normal ovulation in C. elegans.
- DOI:10.1016/j.ydbio.2018.01.009
- 发表时间:2018-03-15
- 期刊:
- 影响因子:2.7
- 作者:McGovern M;Castaneda PG;Pekar O;Vallier LG;Cram EJ;Hubbard EJA
- 通讯作者:Hubbard EJA
Functional Insights into Protein Kinase A (PKA) Signaling from C. elegans.
- DOI:10.3390/life12111878
- 发表时间:2022-11-14
- 期刊:
- 影响因子:3.2
- 作者:Sadeghian, Fereshteh;Castaneda, Perla G.;Amin, Mustafi R.;Cram, Erin J.
- 通讯作者:Cram, Erin J.
Atf-6 Regulates Lifespan through ER-Mitochondrial Calcium Homeostasis.
- DOI:10.1016/j.celrep.2020.108125
- 发表时间:2020-09-08
- 期刊:
- 影响因子:8.8
- 作者:Burkewitz K;Feng G;Dutta S;Kelley CA;Steinbaugh M;Cram EJ;Mair WB
- 通讯作者:Mair WB
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Erin Jean Cram其他文献
Erin Jean Cram的其他文献
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{{ truncateString('Erin Jean Cram', 18)}}的其他基金
Characterization of a novel regulator of cell migration
新型细胞迁移调节剂的表征
- 批准号:
8306781 - 财政年份:2008
- 资助金额:
$ 33.46万 - 项目类别:
Characterization of a novel regulator of cell migration
新型细胞迁移调节剂的表征
- 批准号:
7797845 - 财政年份:2008
- 资助金额:
$ 33.46万 - 项目类别:
Characterization of a novel regulator of cell migration
新型细胞迁移调节剂的表征
- 批准号:
8114984 - 财政年份:2008
- 资助金额:
$ 33.46万 - 项目类别:
Characterization of a novel regulator of cell migration
新型细胞迁移调节剂的表征
- 批准号:
7666910 - 财政年份:2008
- 资助金额:
$ 33.46万 - 项目类别:
Characterization of a novel regulator of cell migration
新型细胞迁移调节剂的表征
- 批准号:
7903147 - 财政年份:2008
- 资助金额:
$ 33.46万 - 项目类别:
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