Collaborative Research: Uncovering How Riboswitches Exploit Out-of-Equilibrium RNA Folding Pathways to Make Genetic Decisions

合作研究:揭示核糖开关如何利用非平衡 RNA 折叠途径做出遗传决策

基本信息

  • 批准号:
    1914567
  • 负责人:
  • 金额:
    $ 35.16万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Continuing Grant
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-08-15 至 2024-03-31
  • 项目状态:
    已结题

项目摘要

This work will uncover new principles by which riboswitch RNAs exploit out-of-equilibrium RNA folding and ligand binding to make genetic decisions. The tools developed will also be applicable to understanding the role of co-transcriptional folding and assembly of ribozymes, regulatory RNA structures within non-coding and coding RNAs, and assembly of RNA-protein complexes such as the ribosome and spliceosome. These studies will also contribute understanding of the physical principles of out-of- equilibrium co-transcriptional RNA folding, help address long-standing questions about how dynamic RNA structures coordinate genetic processes, and shed light on how natural RNAs exploit out-of- equilibrium mechanisms to efficiently fold on extremely rugged free-energy landscapes. Since co-transcriptional RNA folding happens every time an RNA is synthesized, the broader impacts of this research include developing general principles and techniques that can be used to understand a wide array of fundamental cellular processes from gene expression to regulation. The study of riboswitches also has several broader impacts towards societal goals, since they can be used as biosensors within new molecular diagnostics, and they are important targets for new classes of antibiotics. Broader impacts of integrated research and education will come from a multi-pronged plan including conducting demonstrations of riboswitch diagnostics to school-age groups, mentorship of undergraduate researchers, and delivering hands-on tutorials of computational RNA folding approaches to broader scientific communities.The overarching goals of this proposal are to: (i) Uncover detailed mechanisms of how ligand binding bifurcates out-of-equilibrium RNA cotranscriptional folding pathways to enact genetic decisions in riboswitch RNAs; and (ii) Develop and apply new hybrid experimental-computational frameworks that can reconstruct RNA cotranscriptional folding pathways at the secondary and tertiary structure levels. The education plan focuses on integrating this research into hands-on demonstration activities targeted towards school age children, undergraduate researcher mentorship, and hands-on training tutorials for the broader scientific community. The post-genomic era has ushered in a new appreciation that RNAs play central roles in regulating, maintaining and defending the genomes of all organisms. However, a critical knowledge gap remains: we have relatively little understanding of the dynamic folding pathways that RNAs undergo as they are being synthesized during transcription, thus hindering our fundamental understanding of how RNA structures enact critical cellular functions such as catalysis, gene expression regulation, and cellular sensing. To address this gap, the PIs recently innovated and validated a hybrid experimental-computational approach that uses high-throughput RNA structure chemical probing data with computational algorithms to generate two and three-dimensional models of RNA cotranscriptional folding pathways. One central objective of this proposal is to extend this approach to incorporate more complex RNA structures and interactions such as pseudoknots relevant to a broad range of functional cellular RNAs. The second is to uncover biophysical principles of how out-of-equilibrium RNA fluctuations during cotranscriptional folding influence RNA function. The latter will be pursued through the use of riboswitch RNAs as model systems, which make ligand-mediated genetic decisions, use the dynamic formation of broadly utilized RNA structures to do so, and have broader impact relevance for fundamental biology and biotechnologies.This project is being jointly supported by the Physics of Living Systems program in the Division of Physics and the Molecular Biophysics program in the Division of Molecular and Cellular Biosciences.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
这项工作将揭示核糖体开关RNA利用非平衡RNA折叠和配体结合来做出遗传决定的新原理。开发的工具也将适用于理解核酶的共转录折叠和组装的作用,非编码和编码RNA中的调节RNA结构,以及RNA-蛋白质复合物(如核糖体和剪接体)的组装。这些研究也将有助于理解非平衡共转录RNA折叠的物理原理,帮助解决长期存在的关于动态RNA结构如何协调遗传过程的问题,并阐明天然RNA如何利用非平衡机制在极端崎岖的自由能环境中有效折叠。由于每次合成RNA时都会发生共转录RNA折叠,因此本研究的更广泛影响包括开发可用于理解从基因表达到调控的一系列基本细胞过程的一般原理和技术。核开关的研究对社会目标也有一些更广泛的影响,因为它们可以在新的分子诊断中用作生物传感器,并且它们是新型抗生素的重要靶点。综合研究和教育的更广泛影响将来自一个多管齐下的计划,包括向学龄群体演示核糖开关诊断,指导本科生研究人员,以及向更广泛的科学界提供计算RNA折叠方法的实践教程。本提案的总体目标是:(i)揭示配体结合如何使不平衡RNA共转录折叠途径分叉,从而在核糖开关RNA中制定遗传决策的详细机制;(ii)开发和应用新的混合实验-计算框架,可以在二级和三级结构水平上重建RNA共转录折叠途径。教育计划的重点是将这项研究整合到针对学龄儿童的实践示范活动、本科生研究人员指导以及面向更广泛的科学界的实践培训教程中。后基因组时代带来了一种新的认识,即rna在调节、维持和保护所有生物体的基因组方面发挥着核心作用。然而,一个关键的知识缺口仍然存在:我们对RNA在转录过程中合成时所经历的动态折叠途径的了解相对较少,从而阻碍了我们对RNA结构如何发挥关键细胞功能(如催化、基因表达调控和细胞传感)的基本理解。为了解决这一差距,pi最近创新并验证了一种混合实验-计算方法,该方法使用高通量RNA结构化学探测数据和计算算法来生成RNA共转录折叠途径的二维和三维模型。本提案的一个中心目标是将这种方法扩展到更复杂的RNA结构和相互作用,如与广泛的功能性细胞RNA相关的假结。二是揭示协同转录折叠过程中失衡RNA波动如何影响RNA功能的生物物理原理。后者将通过使用核糖开关RNA作为模型系统来实现,该系统通过配体介导的遗传决策,使用广泛使用的RNA结构的动态形成来实现这一目标,并对基础生物学和生物技术具有更广泛的影响。该项目由物理系的生命系统物理学项目和分子与细胞生物科学系的分子生物物理学项目共同支持。该奖项反映了美国国家科学基金会的法定使命,并通过使用基金会的知识价值和更广泛的影响审查标准进行评估,被认为值得支持。

项目成果

期刊论文数量(2)
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 }}

Julius Lucks其他文献

Julius Lucks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('Julius Lucks', 18)}}的其他基金

Transitions: Evolving our Understanding of Dynamic RNA Folding and Function
转变:加深我们对动态 RNA 折叠和功能的理解
  • 批准号:
    2310382
  • 财政年份:
    2023
  • 资助金额:
    $ 35.16万
  • 项目类别:
    Standard Grant
URoL:ASC: The design, development, and societal impact of rapid, in-home, water quality biosensors
URoL:ASC:快速家用水质生物传感器的设计、开发和社会影响
  • 批准号:
    2319427
  • 财政年份:
    2023
  • 资助金额:
    $ 35.16万
  • 项目类别:
    Standard Grant
NRT-URoL: Synthesizing Biology Across Scales – A Convergent Synthetic Biology Training Program
NRT-URoL:跨尺度合成生物学 — 融合合成生物学培训计划
  • 批准号:
    2021900
  • 财政年份:
    2020
  • 资助金额:
    $ 35.16万
  • 项目类别:
    Standard Grant
RAPID: Point-of-Need Detection of COVID-19 using CRISPR-Enabled Cell-Free Synthetic Biology
RAPID:使用支持 CRISPR 的无细胞合成生物学对 COVID-19 进行定点检测
  • 批准号:
    2028651
  • 财政年份:
    2020
  • 资助金额:
    $ 35.16万
  • 项目类别:
    Standard Grant
RAPID: Collaborative Research: A cell-free synthetic biology platform for water quality monitoring - field testing and validation at the Camp Fire site in Paradise, California
RAPID:协作研究:用于水质监测的无细胞合成生物学平台 - 在加利福尼亚州天堂市 Camp Fire 现场进行现场测试和验证
  • 批准号:
    1929912
  • 财政年份:
    2019
  • 资助金额:
    $ 35.16万
  • 项目类别:
    Standard Grant
GOALI: Advanced biomanufacturing with inducible feedback promoters
目标:具有诱导反馈启动子的先进生物制造
  • 批准号:
    1803747
  • 财政年份:
    2018
  • 资助金额:
    $ 35.16万
  • 项目类别:
    Standard Grant
CAREER: Uncovering Quantitative Design Principles of RNA Regulators For Synthetic Biology
职业:揭示合成生物学 RNA 调节剂的定量设计原理
  • 批准号:
    1650040
  • 财政年份:
    2016
  • 资助金额:
    $ 35.16万
  • 项目类别:
    Continuing Grant
CAREER: Uncovering Quantitative Design Principles of RNA Regulators For Synthetic Biology
职业:揭示合成生物学 RNA 调节剂的定量设计原理
  • 批准号:
    1452441
  • 财政年份:
    2015
  • 资助金额:
    $ 35.16万
  • 项目类别:
    Continuing Grant
The Nuts and Bolts of Bioengineered Systems: A Workshop on Standards in Synthetic Biology; Valencia, Spain- March 8-10, 2015
生物工程系统的具体细节:合成生物学标准研讨会;
  • 批准号:
    1523345
  • 财政年份:
    2015
  • 资助金额:
    $ 35.16万
  • 项目类别:
    Standard Grant
Dynamic Control of Glycan Biosynthesis with Synthetic RNA Circuitry
利用合成 RNA 电路动态控制聚糖生物合成
  • 批准号:
    1402843
  • 财政年份:
    2014
  • 资助金额:
    $ 35.16万
  • 项目类别:
    Standard Grant

相似国自然基金

Research on Quantum Field Theory without a Lagrangian Description
  • 批准号:
    24ZR1403900
  • 批准年份:
    2024
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
Cell Research
  • 批准号:
    31224802
  • 批准年份:
    2012
  • 资助金额:
    24.0 万元
  • 项目类别:
    专项基金项目
Cell Research
  • 批准号:
    31024804
  • 批准年份:
    2010
  • 资助金额:
    24.0 万元
  • 项目类别:
    专项基金项目
Cell Research (细胞研究)
  • 批准号:
    30824808
  • 批准年份:
    2008
  • 资助金额:
    24.0 万元
  • 项目类别:
    专项基金项目
Research on the Rapid Growth Mechanism of KDP Crystal
  • 批准号:
    10774081
  • 批准年份:
    2007
  • 资助金额:
    45.0 万元
  • 项目类别:
    面上项目

相似海外基金

Collaborative Research: Uncovering the adaptive origins of fossil apes through the application of a transdisciplinary approach
合作研究:通过应用跨学科方法揭示类人猿化石的适应性起源
  • 批准号:
    2316612
  • 财政年份:
    2024
  • 资助金额:
    $ 35.16万
  • 项目类别:
    Standard Grant
Collaborative Research: Uncovering the adaptive origins of fossil apes through the application of a transdisciplinary approach
合作研究:通过应用跨学科方法揭示类人猿化石的适应性起源
  • 批准号:
    2316615
  • 财政年份:
    2024
  • 资助金额:
    $ 35.16万
  • 项目类别:
    Standard Grant
Collaborative Research: Uncovering the adaptive origins of fossil apes through the application of a transdisciplinary approach
合作研究:通过应用跨学科方法揭示类人猿化石的适应性起源
  • 批准号:
    2316614
  • 财政年份:
    2024
  • 资助金额:
    $ 35.16万
  • 项目类别:
    Standard Grant
Collaborative Research: HNDS-I. Mobility Data for Communities (MD4C): Uncovering Segregation, Climate Resilience, and Economic Development from Cell-Phone Records
合作研究:HNDS-I。
  • 批准号:
    2420945
  • 财政年份:
    2024
  • 资助金额:
    $ 35.16万
  • 项目类别:
    Standard Grant
Collaborative Research: Uncovering the adaptive origins of fossil apes through the application of a transdisciplinary approach
合作研究:通过应用跨学科方法揭示类人猿化石的适应性起源
  • 批准号:
    2316613
  • 财政年份:
    2024
  • 资助金额:
    $ 35.16万
  • 项目类别:
    Standard Grant
Collaborative Research: RUI: Uncovering eusocial pathways and consequences: Phylogenomics, morphological, and molecular evolution in Synalpheus snapping shrimps.
合作研究:RUI:揭示真社会途径和后果:鳄虾的系统基因组学、形态学和分子进化。
  • 批准号:
    2345470
  • 财政年份:
    2023
  • 资助金额:
    $ 35.16万
  • 项目类别:
    Standard Grant
Collaborative Research: Uncovering and Enhancing Pathways to Psychological Safety at Work for Racial Minority Women
合作研究:发现和加强少数族裔女性工作心理安全的途径
  • 批准号:
    2243905
  • 财政年份:
    2023
  • 资助金额:
    $ 35.16万
  • 项目类别:
    Standard Grant
Collaborative Research: Uncovering the Effects of Body-Worn Cameras on Officer and Community Outcomes
合作研究:揭示随身摄像头对警官和社区结果的影响
  • 批准号:
    2317448
  • 财政年份:
    2023
  • 资助金额:
    $ 35.16万
  • 项目类别:
    Standard Grant
Collaborative Research: Uncovering Biology Department Cultural Commitments to Graduate Student Teaching Professional Development
合作研究:揭示生物学系对研究生教学专业发展的文化承诺
  • 批准号:
    2300999
  • 财政年份:
    2023
  • 资助金额:
    $ 35.16万
  • 项目类别:
    Standard Grant
Collaborative Research: Seed-fungal interactions: uncovering functional specificity and primary symbionts as key drivers of tropical tree recruitment
合作研究:种子-真菌相互作用:揭示功能特异性和主要共生体作为热带树木补充的关键驱动因素
  • 批准号:
    2231761
  • 财政年份:
    2023
  • 资助金额:
    $ 35.16万
  • 项目类别:
    Standard Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了