Investigating Mechanisms of RNA Polymerase II Transcription and Regulation Using Single-molecule Fluorescence
利用单分子荧光研究 RNA 聚合酶 II 转录和调控的机制
基本信息
- 批准号:1244518
- 负责人:
- 金额:$ 79.59万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Continuing Grant
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-02-01 至 2018-01-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Intellectual Merit: The process of mRNA synthesis (transcription) is a principle control point for regulating gene expression during growth, development, and normal cellular metabolism. The first step in transcription is formation of a complex of proteins at the promoter of the DNA template. The goal of this project is to investigate the assembly mechanism, dynamics, and heterogeneity of human transcription factor/DNA complexes, and how these parameters contribute to transcriptional control. This research will take advantage of single-molecule fluorescence techniques, which have emerged as essential contributors to revealing the dynamic behavior, conformational states, and heterogeneity of biological complexes, thus providing unprecedented insight into their function. Specifically, studies will investigate human HMGB1, a biologically essential architectural protein that facilitates the formation of protein/DNA complexes important in transcriptional regulation by dynamically binding and bending DNA. The mechanism by which HMGB1 binds and distorts DNA, and how this activity facilitates DNA binding by the transcriptional activator protein p53 will be determined. The research will also investigate the parameters that define the assembly and activity of complexes containing human RNA polymerase II, general transcription factors, and promoter DNA. Fundamental questions about the macromolecular interactions that govern the onset of transcription will be answered. The results from the research will be integrated with previously published biochemical and cell-based studies to provide a comprehensive view of the mechanism by which HMGB1 functions and how RNA polymerase II complexes assemble and transcribe.Broader impacts: The future of science is intimately tied to integrating research and education. Graduate and undergraduate students will perform the research in this project, and significant effort will be made in training these students in experimental design, interpretation of data, creative thought, preparation of manuscripts, and oral presentations. Importantly, efforts will continue to be made to recruit underrepresented minority students into the laboratory. The project also contains an educational component. An experimental module for an undergraduate laboratory course will be developed and implemented. It will teach the relationship between fluorescence energy resonance transfer efficiency and distance between fluorophores in a discovery-based experiment emphasizing experimental design, application of acquired knowledge, data interpretation, and literature searches.
智力优势:mRNA合成(转录)过程是生长、发育和正常细胞代谢过程中调节基因表达的主要控制点。 转录的第一步是在DNA模板的启动子处形成蛋白质复合物。本项目的目标是研究人类转录因子/DNA复合物的组装机制、动力学和异质性,以及这些参数如何有助于转录控制。这项研究将利用单分子荧光技术,这些技术已经成为揭示生物复合物的动态行为,构象状态和异质性的重要贡献者,从而为它们的功能提供前所未有的洞察力。具体而言,研究将调查人类HMGB 1,一种生物学上必需的建筑蛋白,通过动态结合和弯曲DNA促进蛋白质/DNA复合物的形成,这在转录调控中很重要。HMGB 1结合和扭曲DNA的机制,以及这种活性如何通过转录激活蛋白p53促进DNA结合将被确定。该研究还将调查定义包含人类RNA聚合酶II,一般转录因子和启动子DNA的复合物的组装和活性的参数。关于大分子相互作用的基本问题,管理转录的开始将得到回答。这项研究的结果将与先前发表的生物化学和细胞研究相结合,以全面了解HMGB 1的功能机制以及RNA聚合酶II复合物如何组装和转录。更广泛的影响:科学的未来与整合研究和教育密切相关。研究生和本科生将在本项目中进行研究,并在训练这些学生在实验设计,数据解释,创造性思维,准备手稿和口头报告的显着努力。重要的是,将继续努力招收代表性不足的少数民族学生进入实验室。该项目还包括教育部分。将开发和实施一个本科生实验室课程的实验模块。它将在一个以发现为基础的实验中教授荧光能量共振转移效率和荧光团之间距离之间的关系,强调实验设计,所获得知识的应用,数据解释和文献检索。
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 }}
Jennifer Kugel其他文献
Jennifer Kugel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('Jennifer Kugel', 18)}}的其他基金
Investigating mechanisms of RNA polymerase II transcription and regulation using single molecule fluorescence
使用单分子荧光研究 RNA 聚合酶 II 转录和调节的机制
- 批准号:
2242824 - 财政年份:2023
- 资助金额:
$ 79.59万 - 项目类别:
Standard Grant
Investigating Mechanisms of RNA Polymerase II Transcription and Regulation Using Single Molecule Fluorescence
使用单分子荧光研究 RNA 聚合酶 II 转录和调节的机制
- 批准号:
1817442 - 财政年份:2018
- 资助金额:
$ 79.59万 - 项目类别:
Standard Grant
Mechanism and Regulation of Core Promoter Recognition and Promoter Escape during Transcription by RNA Polymerase II
RNA聚合酶II转录过程中核心启动子识别和启动子逃逸的机制和调控
- 批准号:
0919935 - 财政年份:2009
- 资助金额:
$ 79.59万 - 项目类别:
Standard Grant
Mechanism and Regulation of Early Trasncription by RNA polymerase II
RNA聚合酶II早期转录的机制和调控
- 批准号:
0517296 - 财政年份:2005
- 资助金额:
$ 79.59万 - 项目类别:
Continuing Grant
相似国自然基金
Exploring the Intrinsic Mechanisms of CEO Turnover and Market
- 批准号:
- 批准年份:2024
- 资助金额:万元
- 项目类别:外国学者研究基金
Exploring the Intrinsic Mechanisms of CEO Turnover and Market Reaction: An Explanation Based on Information Asymmetry
- 批准号:W2433169
- 批准年份:2024
- 资助金额:万元
- 项目类别:外国学者研究基金项目
相似海外基金
CAREER: Probing structural dynamics and regulatory mechanisms of RNA-guided CRISPR-Cas12 endonucleases and their analogues
职业:探索 RNA 引导的 CRISPR-Cas12 核酸内切酶及其类似物的结构动力学和调控机制
- 批准号:
2339799 - 财政年份:2024
- 资助金额:
$ 79.59万 - 项目类别:
Continuing Grant
The Effect and Molecular Mechanisms of HIV-induced Host RNA Modification
HIV诱导宿主RNA修饰的作用及分子机制
- 批准号:
24K18453 - 财政年份:2024
- 资助金额:
$ 79.59万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Deciphering newly uncovered mechanisms of fluid regulation in bacterial RNA-protein networks
破译细菌 RNA-蛋白质网络中新发现的液体调节机制
- 批准号:
2349832 - 财政年份:2024
- 资助金额:
$ 79.59万 - 项目类别:
Standard Grant
Mechanisms of messenger RNA splicing and RNA processing regulation
信使RNA剪接和RNA加工调控机制
- 批准号:
10623834 - 财政年份:2023
- 资助金额:
$ 79.59万 - 项目类别:
Elucidating pathogenic mechanisms of heart failure through RNA metabolism and protein-protein interaction mediated by transcriptional modulator IkBz
通过转录调节剂 IkBz 介导的 RNA 代谢和蛋白质-蛋白质相互作用阐明心力衰竭的致病机制
- 批准号:
23K07501 - 财政年份:2023
- 资助金额:
$ 79.59万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Mechanisms of viral RNA maturation by co-opting cellular exonucleases
通过选择细胞核酸外切酶使病毒 RNA 成熟的机制
- 批准号:
10814079 - 财政年份:2023
- 资助金额:
$ 79.59万 - 项目类别:
Mechanisms driving Autosomal Dominant Polycystic Kidney Disease: The novel role of the RNA-binding protein ANKHD1.
常染色体显性多囊肾病的驱动机制:RNA 结合蛋白 ANKHD1 的新作用。
- 批准号:
MR/T04201X/2 - 财政年份:2023
- 资助金额:
$ 79.59万 - 项目类别:
Fellowship
Mechanisms underlying circular RNA biogenesis in Alzheimer’s disease related genes
阿尔茨海默病相关基因中环状 RNA 生物发生的机制
- 批准号:
10665204 - 财政年份:2023
- 资助金额:
$ 79.59万 - 项目类别:
Elucidating the mechanisms of alphavirus subgenomic RNA translation
阐明甲病毒亚基因组 RNA 翻译机制
- 批准号:
10678281 - 财政年份:2023
- 资助金额:
$ 79.59万 - 项目类别:
Cardioprotective mechanisms of novel noncoding RNA in myocardial infarction
新型非编码RNA对心肌梗死的心脏保护机制
- 批准号:
10660164 - 财政年份:2023
- 资助金额:
$ 79.59万 - 项目类别: