Deciphering mechanisms that drive collective cell migration
破译驱动集体细胞迁移的机制
基本信息
- 批准号:10917532
- 负责人:
- 金额:$ 32.87万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-01 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalActinsBiochemicalBiocompatible MaterialsBiological AssayBiophysical ProcessBiophysicsBreast Cancer CellCell modelCell physiologyCellsCellular StructuresChemicalsChronicCollaborationsCouplingCuesCytoskeletonDecision MakingEGF geneElementsEnvironmentEpidermal Growth Factor ReceptorEpitheliumEventFluorescence Resonance Energy TransferFoundationsGeneticGoalsGrowth FactorHealthHumanHuman DevelopmentImpairmentIndividualIntercellular JunctionsInterventionKnowledgeLinkMalignant NeoplasmsMethodsMolecularMonitorMotionMovementPLC gamma1PathologicPathologyPathway interactionsPatternProcessReporterSignal TransductionStimulusTissuesTraction Force MicroscopyTranslatingTravelWorkbiophysical toolscell behaviorcell motilityexperimental studyhealinghuman tissueinnovationinsightkeratinocytemigrationnoveloptogeneticsrepairedspatiotemporaltissue repairtooltransmission process
项目摘要
PROJECT SUMMARY
Collective cell migration is the most prevalent form of cell migration in the body; it is involved in the construction
and repair of almost all human tissues. Previous work by the PIs has provided novel insight on the hierarchy of
individual cell behaviors and intracellular signals that drive collective migration. This work identified activation of
the intracellular signal PLCg1 as strongly correlated with increased collective migration and cell migration
persistence. The proposed study aims to elucidate the mechanisms by which PLCg1 drives collective migration
and will yield both novel tools and knowledge that may be applied to control this process. We will achieve this
goal by:
1) Determining the mechanism(s) by which PLCg1 activation yields cytoskeletal remodeling. We will develop
a FRET-based PLCg1 reporter and identify the downstream effectors of PLCg1 that drive cytoskeletal
rearrangement, a critical component of cell movement.
2) Elucidating the biophysical mechanisms by which PLCg1 activation translates into directed collective
migration. We will develop cellular models with varying levels of constitutively active PLCg1 and apply
traction force microscopy to analyze how cytoskeletal forces are transmitted to yield collective cell
movement.
3) Determining optimal patterns and extent of PLCg1 activation needed for robust collective migration. We
will develop an optogenetic approach to stimulate different spatio-temporal dynamics of PLCg1 activation
during directed keratinocyte migration.
By employing a combination of innovative molecular and biophysical tools, we aim to uncover mechanistic
knowledge that allows us to gain control over collective epithelial migration. Identifying the pathway(s) by which
PLCg1 activation connects to downstream signals, as well as its spatial and temporal dynamics within the
collective sheet, provides opportunities to regulate both healthy and pathological collective migration across a
range of tissues and pathologies. Elucidation of these pathways and cues provides an important foundation for
targeting specific elements to induce collective movement in conditions where it is impaired (e.g., chronic would
healing) or to halt collective movement in conditions where it is pathological (e.g., cancer).
项目总结
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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Pamela K Kreeger其他文献
Pamela K Kreeger的其他文献
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{{ truncateString('Pamela K Kreeger', 18)}}的其他基金
The role of multi-cellular aggregates vs. individual tumor cells in metastasis of high-grade serous ovarian cancer
多细胞聚集体与单个肿瘤细胞在高级别浆液性卵巢癌转移中的作用
- 批准号:
9980087 - 财政年份:2020
- 资助金额:
$ 32.87万 - 项目类别:
The role of multi-cellular aggregates vs. individual tumor cells in metastasis of high-grade serous ovarian cancer
多细胞聚集体与单个肿瘤细胞在高级别浆液性卵巢癌转移中的作用
- 批准号:
10232305 - 财政年份:2020
- 资助金额:
$ 32.87万 - 项目类别:
The role of multi-cellular aggregates vs. individual tumor cells in metastasis of high-grade serous ovarian cancer
多细胞聚集体与单个肿瘤细胞在高级别浆液性卵巢癌转移中的作用
- 批准号:
10553590 - 财政年份:2020
- 资助金额:
$ 32.87万 - 项目类别:
Impact of soluble and physical stimuli on tumor angiogenesis and drug sensitivity
可溶性和物理刺激对肿瘤血管生成和药物敏感性的影响
- 批准号:
9015927 - 财政年份:2015
- 资助金额:
$ 32.87万 - 项目类别:
Impact of soluble and physical stimuli on tumor angiogenesis and drug sensitivity
可溶性和物理刺激对肿瘤血管生成和药物敏感性的影响
- 批准号:
9186999 - 财政年份:2015
- 资助金额:
$ 32.87万 - 项目类别:
Analysis of how quantitative cellular network variation impacts tumor progression
分析定量细胞网络变化如何影响肿瘤进展
- 批准号:
8754209 - 财政年份:2014
- 资助金额:
$ 32.87万 - 项目类别:
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Priority Programmes
STRUCTURE/INTERACTIONS OF ACTINS AND ACTIN-BINDING PROTEIN
肌动蛋白和肌动蛋白结合蛋白的结构/相互作用
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