Probing relationships between DNA methylation and cellular senescence with high-throughput CRISPR-based epigenetic editing
利用基于 CRISPR 的高通量表观遗传编辑探索 DNA 甲基化与细胞衰老之间的关系
基本信息
- 批准号:10593233
- 负责人:
- 金额:$ 19.38万
- 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:2022-12-01 至 2024-11-30
- 项目状态:已结题
- 来源:
- 关键词:AccelerationActive SitesAddressAffectAgeAgingAutomobile DrivingBiologicalBiological ProcessBiologyCRISPR screenCRISPR/Cas technologyCell AgingCell physiologyCellsClustered Regularly Interspaced Short Palindromic RepeatsCoupledDNADNA MethylationDataDepositionDiseaseElementsEngineeringEpigenetic ProcessExhibitsFrequenciesFutureGene ExpressionGene SilencingGenomeGenomicsGoldGuide RNAHealthHumanIn VitroIndividualInflammationLibrariesLinkMesenchymal Stem CellsMethodologyMethodsMethylationModelingModificationMolecular ConformationMorphologyOrganismOutcomeOutputPhenotypePlayPopulationProcessProliferatingProteinsPublishingRNA libraryRoleSignal InductionSiteSortingSpecific qualifier valueSystemTechniquesTechnologyTestingTissuesUntranslated RNAValidationWorkWritingagedbisulfite sequencingcell agecell behaviorcell typecellular developmentcellular engineeringcombinatorialepigenomeepigenomicsgenome-widegenomic locushigh throughput screeninginsightinterestmethylomenext generation sequencingnucleaseresponsesenescencestandard measuretechnology platformtooltranscriptome sequencingwhole genome
项目摘要
ABSTRACT
Cellular senescence is a phenomenon associated with aging, wherein cells stop proliferating and secrete
factors which may impact the function of surrounding cells and tissues. Although epigenetic readouts, and in
particular DNA methylation (CpGme), have found to be associated with aging and cellular senescence, it remains
undetermined whether accumulated changes in CpGme are merely correlated with senescence or whether they
play a causal role in driving it. To answer this question, we will combine next-generation sequencing techniques
along with CRISPR-based CpGme editing and CRISPR screens to elucidate the causative associations between
CpGme sites across the genome and cellular senescence.
In Aim 1, we will assess CpGme sites of interest for effect on cellular senescence with a high-throughput
CRISPR screen. Using a CRISPR molecule capable of depositing CpGme, it is possible to generate a population
of cells, each with CpGme modified at a particular site. By characterizing how these CpGme modifications
influence the entry rate into senescence, we will identify CpGme sites that causally affect senescence.
In Aim 2, we will dissect how the most active sites operate to affect senescence. This will be done by inducing
CpGme at the target sites and observing how this influences genomic CpGme and gene expression profiles,
which will provide mechanistic understanding of how the perturbations we make affect cellular function. We will
develop methods to more broadly apply CpGme editing to control cellular senescence. The work will illuminate
an important process associated with aging and will provide new tools to for understanding how epigenetics
impacts biological function, as well as how we can engineer cells to optimize health in the future.
摘要
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
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Lei Stanley Qi其他文献
Lei Stanley Qi的其他文献
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{{ truncateString('Lei Stanley Qi', 18)}}的其他基金
Development of multi-color 3D super-localization LiveFISH and LiveFISH PAINT to investigate the chromatin dynamics at any genomic scale
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10725002 - 财政年份:2023
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10431227 - 财政年份:2022
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A Cas13d-based screening approach to engineer exhaustion-resistant CAR T cells
基于 Cas13d 的筛选方法来设计抗耗竭 CAR T 细胞
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10571868 - 财政年份:2022
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High resolution dissection of oncogene enhancer networks via CRISPR screening and live-cell imaging.
通过 CRISPR 筛选和活细胞成像对癌基因增强子网络进行高分辨率解剖。
- 批准号:
10522013 - 财政年份:2022
- 资助金额:
$ 19.38万 - 项目类别:
High resolution dissection of oncogene enhancer networks via CRISPR screening and live-cell imaging.
通过 CRISPR 筛选和活细胞成像对癌基因增强子网络进行高分辨率解剖。
- 批准号:
10671756 - 财政年份:2022
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$ 19.38万 - 项目类别:
Examining COVID-19 in Down Syndrome Patients Using Human iPSC-Derived Organoids
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10241207 - 财政年份:2021
- 资助金额:
$ 19.38万 - 项目类别:
Modeling Tyrosine Kinase Inhibitor-Induced Vascular Dysfunction Using Human iPSCs
使用人 iPSC 模拟酪氨酸激酶抑制剂诱导的血管功能障碍
- 批准号:
10518663 - 财政年份:2018
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$ 19.38万 - 项目类别:
Human iPSCs for Elucidating Intercellular Crosstalk Signaling in DCM - Diversity Supplement
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- 批准号:
10730997 - 财政年份:2018
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Human iPSCs for Elucidating Intercellular Crosstalk Signaling in Dilated Cardiomyopathy
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10852761 - 财政年份:2018
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$ 19.38万 - 项目类别:
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