Diversity Supplement to Structure/Function of Transcription Complex Regulation to Support Predoctoral Student Christiana Binkley
转录复合体调节结构/功能的多样性补充以支持博士生克里斯蒂娜·宾克利
基本信息
- 批准号:10351034
- 负责人:
- 金额:$ 1.46万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-07-01 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:AbbreviationsActive SitesAddressAmino AcidsAntibioticsAntisense RNABacterial ChromosomesBacterial ModelBacterial RNABindingBiochemicalBiochemical GeneticsBiochemistryBiogenesisBiological AssayBiotechnologyC-terminalCellsChromatinChromatin StructureChromosome StructuresClosure by clampComplexCoupledCouplingCryoelectron MicroscopyCytidineDNADNA Insertion ElementsDNA-Directed RNA PolymeraseDiffuseDiseaseEscherichia coliEukaryotaFamilyFilamentFluorescenceFundingGene Expression RegulationGene SilencingGenetic TranscriptionGoalsHealthHumanIn VitroKnowledgeLearningMapsMediatingMedicineMethodsModelingMolecularMolecular BiologyMolecular ChaperonesMolecular ConformationMycobacterium tuberculosisN-terminalNucleoproteinsNucleotidesOrthologous GenePatternPhenylalanineProkaryotic CellsProtein BiosynthesisRNARNA FoldingRNA chemical synthesisRegulationReporterResearchResolutionRibosomesRoleSaccharomyces cerevisiaeSignal TransductionStressStructureStudentsSystemThermus thermophilusTimeTranscriptTranscription ElongationTranscriptional RegulationTranslationsTriplet Multiple BirthWorkantimicrobialbaseds-DNAgene therapygenetic approachgenome-wideimprovedin vivoinsightmicrobial communitynovelpathogenic microbepre-doctoralprematuresingle moleculestructural biologytime usetoolvirtual
项目摘要
Project Summary/Abstract
The long-term goal of this project is to define the interactions within transcription elongation complexes and
with regulators that cause and control pausing and termination by RNA polymerase. Pausing and premature
termination underlie many aspects of gene regulation in prokaryotes and eukaryotes, including transcription
through chromatin and linkages to RNA maturation and translation. Both the basic mechanisms of pausing
and termination and the mechanisms by which regulators control pausing and termination depend on poorly
understood changes to interactions within the elongation complex. Many of these interactions modulate
conformational changes in RNA polymerase involving mobile modules including the clamp, trigger loop, and
lineage-specific insertions that must achieve particular conformations for efficient transcription. Understand-
ing how regulators promote or inhibit these different conformations will provide key basic knowledge essential
to guide the rational manipulation of regulators for antimicrobials or gene therapies. Knowledge gained about
model bacterial systems also facilitates understanding of highly conserved mechanisms of transcription in
humans. Additionally, bacterial RNA polymerase is a known target of antibiotics, and knowledge about its
functional mechanisms will aid in identifying and characterizing new antibiotics.
A combination of structural, biochemical, and genetic approaches will be used to characterize the interac-
tions in the elongation complex that mediate regulation. New methods for transcription assay by cryo-electron
microscopy, for single-molecule assay of RNA polymerase interactions with RNA structures, regulators, and
ribosomes, and for genome-scale analysis of chromatin structure and elongation complex regulation will be
developed. This combination of approaches will be used to understand connections among progress of the
elongation complex during transcription, the structure of bacterial chromatin, RNA folding, and RNA
translation. The work builds on recent discoveries of the structural basis by which RNA polymerase assists
RNA folding, of the role of H-NS family nucleoprotein filaments in stimulation of pausing and termination
during transcriptional silencing, and of interaction of RNA polymerase with the pioneering ribosome in a
complex called the expressome. The specific aims of the project are to (i) elucidate steps in pausing, termina-
tion, and RNA folding and roles of key RNAP modules; (ii) define structures, patterns, and elongation complex
interactions of H-NS family nucleoprotein filaments; and (iii) determine when the expressome forms and how
it functions during transcript elongation. This integrated research will help build a new understanding of tran-
scriptional regulation by defining how pause and termination signals change elongation complex structure and
activity dynamically and how chromosome structure and translational coupling modulate elongation complex
activity. The impact of these studies will be an improved understanding of elongation complex regulation, with
broad applications to biotechnology, human medicine, and both prokaryotic and eukaryotic molecular biology.
项目总结/摘要
该项目的长期目标是定义转录延伸复合物内的相互作用,
通过RNA聚合酶引起和控制暂停和终止的调节器。暂停和过早
终止是原核生物和真核生物基因调控许多方面的基础,包括转录
通过染色质和连接到RNA成熟和翻译。暂停的基本机制
和终止以及调节器控制暂停和终止的机制依赖于不良的
理解延伸复合物内相互作用的变化。这些相互作用中的许多调节
RNA聚合酶的构象变化涉及移动的模块,包括钳、触发环和
谱系特异性插入,必须实现有效转录的特定构象。你要明白-
研究调节剂如何促进或抑制这些不同的构象将提供关键的基本知识
指导抗菌药物或基因治疗的调节剂的合理操作。获得的知识
模型细菌系统也有助于理解在转录过程中高度保守的转录机制。
人类此外,细菌RNA聚合酶是抗生素的已知靶点,关于其作用的知识也不多。
功能机制将有助于识别和表征新的抗生素。
结构,生物化学和遗传方法的组合将用于表征相互作用,
延伸复合物中的调节调节作用。低温电子转录检测新方法
显微镜,用于RNA聚合酶与RNA结构,调节剂和
核糖体,并为基因组规模的分析染色质结构和延伸复合物的调控将是
开发这种方法的组合将被用来理解的进展之间的联系,
转录过程中的延伸复合物,细菌染色质的结构,RNA折叠和RNA
翻译.这项工作建立在最近发现的RNA聚合酶协助的结构基础上
RNA折叠,H-NS家族核蛋白丝在刺激暂停和终止中的作用
在转录沉默过程中,以及RNA聚合酶与先驱核糖体的相互作用,
称为expressome。该项目的具体目标是:(一)阐明暂停、终止、
RNA折叠和关键RNAP模块的作用;(ii)定义结构,模式和延伸复合物
H-NS家族核蛋白丝的相互作用;和(iii)确定表达体何时形成以及如何形成
它在转录物延伸期间起作用。这一综合研究将有助于建立一个新的理解跨,
通过定义暂停和终止信号如何改变延伸复合体结构,
活性的动态变化以及染色体结构和翻译偶联如何调节延伸复合体
活动这些研究的影响将是对延伸复合物调控的更好理解,
广泛应用于生物技术、人类医学以及原核和真核分子生物学。
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 }}
Robert Landick其他文献
Robert Landick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('Robert Landick', 18)}}的其他基金
Structure/Function of Transcription Complex Regulation
转录复合物调控的结构/功能
- 批准号:
7988507 - 财政年份:2009
- 资助金额:
$ 1.46万 - 项目类别:
Human RNAPII Structure/Function in Pausing & Elongation
暂停中的人类 RNAPII 结构/功能
- 批准号:
7391053 - 财政年份:2006
- 资助金额:
$ 1.46万 - 项目类别:
Human RNAPII Structure/Function in Pausing & Elongation
暂停中的人类 RNAPII 结构/功能
- 批准号:
7094722 - 财政年份:2006
- 资助金额:
$ 1.46万 - 项目类别:
Human RNAPII Structure/Function in Pausing & Elongation
暂停中的人类 RNAPII 结构/功能
- 批准号:
7211464 - 财政年份:2006
- 资助金额:
$ 1.46万 - 项目类别:
Human RNAPII Structure/Function in Pausing & Elongation
暂停中的人类 RNAPII 结构/功能
- 批准号:
7609099 - 财政年份:2006
- 资助金额:
$ 1.46万 - 项目类别:
High-Throughput Identification of RNA polymerase inhibitors in vivo
体内 RNA 聚合酶抑制剂的高通量鉴定
- 批准号:
7169444 - 财政年份:2006
- 资助金额:
$ 1.46万 - 项目类别:
Structure/Function of Transcription Complex RNA Hairpins
转录复合物RNA发夹的结构/功能
- 批准号:
6400682 - 财政年份:1987
- 资助金额:
$ 1.46万 - 项目类别:
STRUCTURE/FUNCTION OF TRANSCRIPTION COMPLEX RNA HAIRPINS
转录复合物 RNA 发夹的结构/功能
- 批准号:
3466376 - 财政年份:1987
- 资助金额:
$ 1.46万 - 项目类别:
STRUCTURE/FUNCTION OF TRANSCRIPTION COMPLEX RNA HAIRPINS
转录复合物 RNA 发夹的结构/功能
- 批准号:
3295256 - 财政年份:1987
- 资助金额:
$ 1.46万 - 项目类别:
相似海外基金
Collaborative Research: Beyond the Single-Atom Paradigm: A Priori Design of Dual-Atom Alloy Active Sites for Efficient and Selective Chemical Conversions
合作研究:超越单原子范式:双原子合金活性位点的先验设计,用于高效和选择性化学转化
- 批准号:
2334970 - 财政年份:2024
- 资助金额:
$ 1.46万 - 项目类别:
Standard Grant
NSF-BSF: Towards a Molecular Understanding of Dynamic Active Sites in Advanced Alkaline Water Oxidation Catalysts
NSF-BSF:高级碱性水氧化催化剂动态活性位点的分子理解
- 批准号:
2400195 - 财政年份:2024
- 资助金额:
$ 1.46万 - 项目类别:
Standard Grant
Collaborative Research: Beyond the Single-Atom Paradigm: A Priori Design of Dual-Atom Alloy Active Sites for Efficient and Selective Chemical Conversions
合作研究:超越单原子范式:双原子合金活性位点的先验设计,用于高效和选择性化学转化
- 批准号:
2334969 - 财政年份:2024
- 资助金额:
$ 1.46万 - 项目类别:
Standard Grant
Mechanochemical synthesis of nanocarbon and design of active sites for oxygen reducton/evolution reactions
纳米碳的机械化学合成和氧还原/演化反应活性位点的设计
- 批准号:
23K04919 - 财政年份:2023
- 资助金额:
$ 1.46万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Creation of porous inorganic frameworks with controlled structure of metal active sites by the building block method.
通过积木法创建具有金属活性位点受控结构的多孔无机框架。
- 批准号:
22KJ2957 - 财政年份:2023
- 资助金额:
$ 1.46万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Catalysis of Juxaposed Active Sites Created in Nanospaces and Their Applications
纳米空间中并置活性位点的催化及其应用
- 批准号:
23K04494 - 财政年份:2023
- 资助金额:
$ 1.46万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Generation of carbon active sites by modifying the oxygen containing functional groups and structures of carbons for utilizing to various catalytic reactions.
通过修饰碳的含氧官能团和结构来产生碳活性位点,用于各种催化反应。
- 批准号:
23K13831 - 财政年份:2023
- 资助金额:
$ 1.46万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
CAREER: CAS: Understanding the Chemistry of Palladium and Silyl Compounds to Design Catalyst Active Sites
职业:CAS:了解钯和甲硅烷基化合物的化学性质以设计催化剂活性位点
- 批准号:
2238379 - 财政年份:2023
- 资助金额:
$ 1.46万 - 项目类别:
Continuing Grant
CAS: Collaborative Research: Tailoring the Distribution of Transient vs. Dynamic Active Sites in Solid-Acid Catalysts and Their Impacts on Chemical Conversions
CAS:合作研究:定制固体酸催化剂中瞬时活性位点与动态活性位点的分布及其对化学转化的影响
- 批准号:
2154399 - 财政年份:2022
- 资助金额:
$ 1.46万 - 项目类别:
Standard Grant
Engineering of Active Sites in Heterogeneous Catalysts for Sustainable Chemical and Fuel Production.
用于可持续化学和燃料生产的多相催化剂活性位点工程。
- 批准号:
RGPIN-2019-06633 - 财政年份:2022
- 资助金额:
$ 1.46万 - 项目类别:
Discovery Grants Program - Individual