Transcriptome Analysis with RNA-Reactive Probes
使用 RNA 反应探针进行转录组分析
基本信息
- 批准号:10793323
- 负责人:
- 金额:$ 4.58万
- 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:2022-05-01 至 2027-04-30
- 项目状态:未结题
- 来源:
- 关键词:AddressAffectBinding SitesBiologicalBiologyCellsChemicalsChemistryClinicalComplexDrug InteractionsFluorescenceFutureGelGoalsHealthHumanLabelLigand BindingLigandsLightMediatingMessenger RNAMetabolite InteractionMethodologyMethodsModificationMolecularPathway interactionsPharmaceutical PreparationsProteinsProteomeRNARNA BindingRNA analysisRNA vaccineReactionReagentResearchResearch PersonnelResolutionSchoolsSiteStructureSulfurSurveysSystemTechnologyTherapeuticTherapeutic AgentsTimeToxic effectUniversitiesWorkbaseclinically relevantimprovedinsightinstrumentinterestnext generationnext generation sequencingnovelnovel strategiesparent grantparent projectprogramssecondary metabolitesmall moleculetherapeutic RNAtherapeutic targettooltranscriptome
项目摘要
Summary of parent project (R35 GM145357)
Work in the last decade from many labs has underlined the critical importance of RNA-mediated
cellular pathways, and clear connections of specific RNAs to human health. RNAs are
increasingly viewed both as appealing therapeutic targets, and as therapeutic agents
themselves. We hypothesize that obtaining a deeper and broader understanding about how
ligands interact with the many RNA species of the cell will provide important new insights into
RNA networks and functions, provide new understanding of how current drugs cause cellular
toxicity, and lend novel insights into improving RNA therapies. We are convinced that the
analysis of RNA interactions transcriptome-wide is essential to future biomedicine.
Unfortunately, methods for assessing RNA interactions directly in the cell lag well behind those
for protein and proteome analysis.
This project will consolidate our RNA work into a broad program that will develop a new set of
RNA-reactive reagents and methods, and will apply them to provide specific, quantitative
information about ligand interactions with the transcriptome. We will develop first-in-class
methods for functionalizing native RNAs at specific sites, and novel strategies for controlling
RNAs with red light. Combining our reactive acyl tools and methods with next-gen sequencing,
we will pinpoint and quantify ligand binding sites in the whole transcriptome. These
methodologies, together termed Reactivity-Based RNA Profiling (RBRP), will be applied to
analyzing off-target RNA binding by known small-molecule drugs with clinically limiting toxicity,
to profiling RNA interactions of endogenous secondary metabolites, and to the analysis of how
modified bases in next-generation mRNA vaccines and therapeutics affect their structures and
interactions in the cell. This work is significant because it seeks answers to system-wide
clinically-relevant questions regarding RNA interactions. Further, it develops the 2’-OH group as
a nearly universal handle for manipulation, conjugation, and study of RNAs, introducing
enabling molecular technologies that will broadly benefit researchers in the fields of RNA
biology and contribute to improving future RNA therapies.
母项目总结(R35 GM145357)
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
RNA Infrastructure Profiling Illuminates Transcriptome Structure in Crowded Spaces.
RNA 基础设施分析阐明了拥挤空间中的转录组结构。
- DOI:10.1101/2023.10.09.561413
- 发表时间:2023
- 期刊:
- 影响因子:0
- 作者:Xiao,Lu;Fang,Linglan;Kool,EricT
- 通讯作者:Kool,EricT
Sulfonylation of RNA 2'-OH groups.
RNA 2'-OH基团的磺酰基。
- DOI:10.1021/acscentsci.2c01237
- 发表时间:2023-03-22
- 期刊:
- 影响因子:18.2
- 作者:Chatterjee, Sayantan;Shioi, Ryuta;Kool, Eric T.
- 通讯作者:Kool, Eric T.
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ERIC T. KOOL其他文献
ERIC T. KOOL的其他文献
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{{ truncateString('ERIC T. KOOL', 18)}}的其他基金
Transcriptome Analysis with RNA-Reactive Probes
使用 RNA 反应探针进行转录组分析
- 批准号:
10406530 - 财政年份:2022
- 资助金额:
$ 4.58万 - 项目类别:
Transcriptome Analysis with RNA-Reactive Probes
使用 RNA 反应探针进行转录组分析
- 批准号:
10602470 - 财政年份:2022
- 资助金额:
$ 4.58万 - 项目类别:
Covalent Profiling of RNA Targets and Off-targets
RNA 靶标和脱靶的共价分析
- 批准号:
10294248 - 财政年份:2019
- 资助金额:
$ 4.58万 - 项目类别:
Covalent Profiling of RNA Targets and Off-targets
RNA 靶标和脱靶的共价分析
- 批准号:
10061624 - 财政年份:2019
- 资助金额:
$ 4.58万 - 项目类别:
Probing the Transcriptome with Multifunctional Acylation Chemistry
用多功能酰化化学探索转录组
- 批准号:
9926279 - 财政年份:2018
- 资助金额:
$ 4.58万 - 项目类别:
Probing the Transcriptome with Multifunctional Acylation Chemistry
用多功能酰化化学探索转录组
- 批准号:
9494223 - 财政年份:2018
- 资助金额:
$ 4.58万 - 项目类别:
Measuring and Modulating Oxidative DNA Damage Surveillance Pathways
测量和调节氧化 DNA 损伤监测途径
- 批准号:
9287818 - 财政年份:2017
- 资助金额:
$ 4.58万 - 项目类别:
Measuring and Modulating Oxidative DNA Damage Surveillance Pathways
测量和调节氧化 DNA 损伤监测途径
- 批准号:
9924487 - 财政年份:2017
- 资助金额:
$ 4.58万 - 项目类别:
Measuring and Modulating DNA Damage Surveillance Pathways
测量和调节 DNA 损伤监测途径
- 批准号:
10617737 - 财政年份:2017
- 资助金额:
$ 4.58万 - 项目类别:
Measuring and Modulating DNA Damage Surveillance Pathways
测量和调节 DNA 损伤监测途径
- 批准号:
10396578 - 财政年份:2017
- 资助金额:
$ 4.58万 - 项目类别:
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