Deep cell history tracking: engineering cells that write their detailed life stories into their DNA to study DNA damage
深度细胞历史追踪:工程细胞将详细的生命故事写入 DNA 中以研究 DNA 损伤
基本信息
- 批准号:10439875
- 负责人:
- 金额:$ 10万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-01 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:AffectAnimalsArchitectureBiologicalCell CycleCell physiologyCellsCharacteristicsCollectionCultured CellsDNADNA DamageDNA damage checkpointDevelopmentDoseEngineeringEventGene ProteinsGenomeGenome StabilityInsertion MutationLeadLifeLong-Term EffectsLongitudinal StudiesMalignant NeoplasmsMammalsMolecularMonitorMutationNucleotidesOpticsPharmaceutical PreparationsPharmacotherapyPhasePhenotypePhysiologicalPopulationRNARecording of previous eventsRecordsResistanceRoleSamplingSignal TransductionTechniquesTechnologyTestingTherapeuticTimeTransgenic MiceWorkWritingXenograft ModelXenograft procedurebaseexperienceexperimental studygenetically modified cellsgenomic locusin vivointerestmolecular phenotypemouse modelnew technologynovel strategiespatient derived xenograft modelpromoterresponsesingle-cell RNA sequencingtissue culturetooltriple-negative invasive breast carcinoma
项目摘要
Project Summary
DNA recording is a recently developed technology that allows cellular signaling events of interest to be followed
over time without removing cells from their physiological context. During a DNA recording experiment, genetically
engineered cells expressing the DNA recorder acquire mutations at a “recording locus” as the result of transient
cellular events, without perturbing their normal phenotype. At the end of the experiment, once their eventual
phenotype is known, cells can be collected and their histories determined by sequencing the recording locus.
The work proposed here will lead to a DNA recorder that is not limited, as current technology is, to recording one
or two cellular events per experiment, but can record dozens of events in parallel, allowing an unbiased
examination of cell history in any context compatible with genetically engineered cells. In this project, the new
DNA recorder will be used to study long-term effects for a cell of experiencing significant spontaneous DNA
damage. Although DNA damage is very well-studied, it has not previously been possible to follow the rare cells
that experience significant spontaneous damage, especially in an in vivo mammalian context. The new DNA
recorder will be developed in stages: First, intracellular recording machinery, based on a pre-existing recorder,
will be created for a small number of cellular events associated with the DNA damage response. Next, the fidelity
of this new recording machinery will be extensively validated in cultured cells and cancer xenografts. Finally, a
new recording architecture will be developed and validated, before being introduced into a transgenic mouse to
identify how spontaneous DNA damage affects cell fate determination during normal development.
项目总结
项目成果
期刊论文数量(0)
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会议论文数量(0)
专利数量(0)
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Theresa Berens Loveless其他文献
Theresa Berens Loveless的其他文献
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{{ truncateString('Theresa Berens Loveless', 18)}}的其他基金
Deep cell history tracking: engineering cells that write their detailed life stories into their DNA to study DNA damage
深度细胞历史追踪:工程细胞将详细的生命故事写入 DNA 中以研究 DNA 损伤
- 批准号:
10899928 - 财政年份:2021
- 资助金额:
$ 10万 - 项目类别:
Deep cell history tracking: engineering cells that write their detailed life stories into their DNA to study DNA damage
深度细胞历史追踪:工程细胞将详细的生命故事写入 DNA 中以研究 DNA 损伤
- 批准号:
10301626 - 财政年份:2021
- 资助金额:
$ 10万 - 项目类别:
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