Generation and characterization of tools for target-specific de novo DNA methylat
目标特异性从头 DNA 甲基化工具的生成和表征
基本信息
- 批准号:9079296
- 负责人:
- 金额:$ 15万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-08-01 至 2016-05-31
- 项目状态:已结题
- 来源:
- 关键词:AreaBindingCell LineCellsClustered Regularly Interspaced Short Palindromic RepeatsDNADNA MethylationDNA Modification MethylasesData SetDatabasesDoxycyclineES Cell LineEngineeringEnhancersEnvironmentEnzymesEpigenetic ProcessFoundationsGenerationsGenomeGenomic SegmentGenomicsGoalsHealthHumanLifeLysineMaintenanceMapsMeasurementMeasuresMethylationMolecular BiologyMusOutcomePeptidesPerformancePromoter RegionsReadingRegulationResolutionSpecificitySystemTranscription CoactivatorWorkWritingbasebisulfite sequencingcell typedensitydesignembryonic stem cellgain of functiongenome-wideinnovationpreventsmall hairpin RNAsmall moleculetooltranscription factor
项目摘要
DESCRIPTION (provided by applicant): The inability to manipulate DNA methylation or other epigenetic marks at will remains one of the biggest constrains in the field of epigenetics. Our goal is to overcome this limitation by designing an innovative approach for targeted manipulation of DNA methylation in a unique cellular system that also enables accurate measurements of such performance. Having the precise temporal and localized control over epigenetic marks will be essential for further dissecting their exact function(s) in genome regulation. The ability to write rather than just read epigenetic marks is the last missing piece t confidently and generally establish functional relationships, control the genome and will therefore have a wide impact on many fields. Over the past five years my lab has been one of the leading groups to map and manipulate DNA methylation at a genome-wide scale and we have accumulated likely the largest database of DNA methylation measurements at single base resolution. We have generated well over 2000 reduced representation bisulfite sequencing (RRBS) and more than 50 whole genome bisulfite sequencing (WGBS) datasets providing us with over a 100 billion CpG methylation measurements across more than a hundred mouse and human cell types. As a result we are confident to state that we know where in the genome DNA methylation can be found and how it is influenced by its genomic environment. Moreover we have created many mouse ES cells lines covering nearly every combination of loss and/or gain of function for the three catalytically active Dnmts (1, 3a and 3b) and their co-factor Dnmt3l. These in turn provide a unique foundation for this proposed study and enables us to most accurately determine efficiencies while controlling confounding factors. We strongly believe that simply engineering tools to write onto the genome without understanding the rules and principles on how this mark can be written in a genomic context will never provide a universal strategy.
描述(由申请人提供):不能随意操纵DNA甲基化或其他表观遗传标记仍然是表观遗传学领域最大的限制之一。我们的目标是通过设计一种创新的方法来克服这一限制,该方法用于在独特的细胞系统中靶向操纵DNA甲基化,并且还能够准确测量这种性能。对表观遗传标记进行精确的时间和局部控制对于进一步剖析其在基因组调控中的确切功能至关重要。书写而不仅仅是阅读表观遗传标记的能力是最后一个缺失的部分,它可以自信地建立功能关系,控制基因组,因此将对许多领域产生广泛的影响。 在过去的五年里,我的实验室一直是在全基因组范围内绘制和操纵DNA甲基化的领导小组之一,我们已经积累了可能是最大的单碱基分辨率DNA甲基化测量数据库。我们已经生成了超过2000个简化代表性亚硫酸氢盐测序(RRBS)和超过50个全基因组亚硫酸氢盐测序(WGBS)数据集,为我们提供了超过1000亿个CpG甲基化测量结果,涉及100多种小鼠和人类细胞类型。因此,我们有信心声明,我们知道在基因组中可以发现DNA甲基化的位置以及它如何受到其基因组环境的影响。此外,我们已经建立了许多小鼠ES细胞系,几乎涵盖了三种催化活性Dnmt(1、3a和3b)及其辅因子Dnmt 31的功能丧失和/或获得的每种组合。这些反过来又为这项拟议的研究提供了一个独特的基础,使我们能够最准确地确定效率,同时控制混杂因素。我们坚信,在不了解如何在基因组背景下写入该标记的规则和原则的情况下,简单地设计工具来写入基因组永远不会提供通用策略。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Alexander Meissner其他文献
Alexander Meissner的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Alexander Meissner', 18)}}的其他基金
Generation and characterization of tools for target-specific de novo DNA methylat
目标特异性从头 DNA 甲基化工具的生成和表征
- 批准号:
8735920 - 财政年份:2013
- 资助金额:
$ 15万 - 项目类别:
Generation and characterization of tools for target-specific de novo DNA methylat
目标特异性从头 DNA 甲基化工具的生成和表征
- 批准号:
8642319 - 财政年份:2013
- 资助金额:
$ 15万 - 项目类别:
Generation and characterization of tools for target-specific de novo DNA methylat
目标特异性从头 DNA 甲基化工具的生成和表征
- 批准号:
9275954 - 财政年份:2013
- 资助金额:
$ 15万 - 项目类别:
Dissecting the establishment and regulation of human pluripotency
剖析人类多能性的建立和调节
- 批准号:
8196106 - 财政年份:2011
- 资助金额:
$ 15万 - 项目类别:
Dissecting the establishment and regulation of human pluripotency
剖析人类多能性的建立和调节
- 批准号:
8306918 - 财政年份:2011
- 资助金额:
$ 15万 - 项目类别:
Dissecting the establishment and regulation of human pluripotency
剖析人类多能性的建立和调节
- 批准号:
8717677 - 财政年份:2011
- 资助金额:
$ 15万 - 项目类别:
Dissecting the establishment and regulation of human pluripotency
剖析人类多能性的建立和调节
- 批准号:
8535278 - 财政年份:2011
- 资助金额:
$ 15万 - 项目类别:
Project 1: Establishment & maintenance of the pluripotent state
项目一:建立
- 批准号:
8535279 - 财政年份:
- 资助金额:
$ 15万 - 项目类别:
相似国自然基金
帽结合蛋白(cap binding protein)调控乙烯信号转导的分子机制
- 批准号:32170319
- 批准年份:2021
- 资助金额:58.00 万元
- 项目类别:面上项目
帽结合蛋白(cap binding protein)调控乙烯信号转导的分子机制
- 批准号:
- 批准年份:2021
- 资助金额:58 万元
- 项目类别:
ID1 (Inhibitor of DNA binding 1) 在口蹄疫病毒感染中作用机制的研究
- 批准号:31672538
- 批准年份:2016
- 资助金额:62.0 万元
- 项目类别:面上项目
番茄EIN3-binding F-box蛋白2超表达诱导单性结实和果实成熟异常的机制研究
- 批准号:31372080
- 批准年份:2013
- 资助金额:80.0 万元
- 项目类别:面上项目
P53 binding protein 1 调控乳腺癌进展转移及化疗敏感性的机制研究
- 批准号:81172529
- 批准年份:2011
- 资助金额:58.0 万元
- 项目类别:面上项目
DBP(Vitamin D Binding Protein)在多发性硬化中的作用和相关机制的蛋白质组学研究
- 批准号:81070952
- 批准年份:2010
- 资助金额:35.0 万元
- 项目类别:面上项目
研究EB1(End-Binding protein 1)的癌基因特性及作用机制
- 批准号:30672361
- 批准年份:2006
- 资助金额:24.0 万元
- 项目类别:面上项目
相似海外基金
Collaborative Research: NSF-BSF: How cell adhesion molecules control neuronal circuit wiring: Binding affinities, binding availability and sub-cellular localization
合作研究:NSF-BSF:细胞粘附分子如何控制神经元电路布线:结合亲和力、结合可用性和亚细胞定位
- 批准号:
2321481 - 财政年份:2024
- 资助金额:
$ 15万 - 项目类别:
Continuing Grant
Collaborative Research: NSF-BSF: How cell adhesion molecules control neuronal circuit wiring: Binding affinities, binding availability and sub-cellular localization
合作研究:NSF-BSF:细胞粘附分子如何控制神经元电路布线:结合亲和力、结合可用性和亚细胞定位
- 批准号:
2321480 - 财政年份:2024
- 资助金额:
$ 15万 - 项目类别:
Continuing Grant
Postdoctoral Fellowship: OPP-PRF: Understanding the Role of Specific Iron-binding Organic Ligands in Governing Iron Biogeochemistry in the Southern Ocean
博士后奖学金:OPP-PRF:了解特定铁结合有机配体在控制南大洋铁生物地球化学中的作用
- 批准号:
2317664 - 财政年份:2024
- 资助金额:
$ 15万 - 项目类别:
Standard Grant
Conformations of musk odorants and their binding to human musk receptors
麝香气味剂的构象及其与人类麝香受体的结合
- 批准号:
EP/X039420/1 - 财政年份:2024
- 资助金额:
$ 15万 - 项目类别:
Research Grant
NPBactID - Differential binding of peptoid functionalized nanoparticles to bacteria for identifying specific strains
NPBactID - 类肽功能化纳米粒子与细菌的差异结合,用于识别特定菌株
- 批准号:
EP/Y029542/1 - 财政年份:2024
- 资助金额:
$ 15万 - 项目类别:
Fellowship
Alkane transformations through binding to metals
通过与金属结合进行烷烃转化
- 批准号:
DP240103289 - 财政年份:2024
- 资助金额:
$ 15万 - 项目类别:
Discovery Projects
I-Corps: Translation Potential of Real-time, Ultrasensitive Electrical Transduction of Biological Binding Events for Pathogen and Disease Detection
I-Corps:生物结合事件的实时、超灵敏电转导在病原体和疾病检测中的转化潜力
- 批准号:
2419915 - 财政年份:2024
- 资助金额:
$ 15万 - 项目类别:
Standard Grant
The roles of a universally conserved DNA-and RNA-binding domain in controlling MRSA virulence and antibiotic resistance
普遍保守的 DNA 和 RNA 结合域在控制 MRSA 毒力和抗生素耐药性中的作用
- 批准号:
MR/Y013131/1 - 财政年份:2024
- 资助金额:
$ 15万 - 项目类别:
Research Grant
CRII: OAC: Development of a modular framework for the modeling of peptide and protein binding to membranes
CRII:OAC:开发用于模拟肽和蛋白质与膜结合的模块化框架
- 批准号:
2347997 - 财政年份:2024
- 资助金额:
$ 15万 - 项目类别:
Standard Grant
How lipid binding proteins shape the activity of nuclear hormone receptors
脂质结合蛋白如何影响核激素受体的活性
- 批准号:
DP240103141 - 财政年份:2024
- 资助金额:
$ 15万 - 项目类别:
Discovery Projects