NSF/BSF: Post-Transcriptional Regulation of Gene Expression: From Molecular Interactions to the Network Level

NSF/BSF:基因表达的转录后调控:从分子相互作用到网络水平

基本信息

  • 批准号:
    2102832
  • 负责人:
  • 金额:
    $ 54万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-09-15 至 2024-08-31
  • 项目状态:
    已结题

项目摘要

Transcription is the first step on the path of protein synthesis and consists of copying a DNA sequence into an RNA sequence. In addition to the transcriptional regulation of gene expression, a regulatory layer exists, known as post-transcriptional regulation. In eukaryotes, micro RNAs (miRNAs) are key mediators of this regulatory network. Post-transcriptional regulation is still poorly understood and many fundamental questions remain open. Some features of miRNA-based regulation make it different from other mechanisms of gene regulation: it is stoichiometric and, thus, competition effects emerge, it occurs in the cytoplasm, and it involves transport of both the regulator and targets. The goal of this project is to understand cellular properties that arise from post-transcriptional regulation across spatiotemporal scales, from the motion and interactions of individual molecules to the network level. This project will support an outreach program at Webber Middle School in Fort Collins, CO. Research experiences for students will be developed in coordination with school teachers and integrated within an established exceptional program therein, namely the Webber’s Aerospace Ventures in Education (WAVE), which offers students an engaging, challenging, and rigorous experience simulating how to organize and conduct extra-planetary exploration with the goal of encouraging students to pursue space science research and future careers within the industry. The collaboration with school teachers will enable valuable innovations to the WAVE curriculum. The main activities will focus on testing for the presence of life using biomarkers of RNA and DNA, attending demonstrations of single-molecule RNA tracking, and evaluating the motion RNA in live cells. The objectives of this project are (i) to dissect the effects of the complex cell environment on post-transcriptional regulation and (ii) to elucidate the crosstalk effects of the post-transcriptional network. The PIs will use optical imaging to track the paths of miRNAs and mRNAs at the single-molecule level in living cells. Experimental trajectories will be analyzed using theoretical and computational approaches that include first passage processes and anomalous diffusion theory for the calculation of kinetic rates coefficients. These coefficients will be employed in mathematical models. The analysis of multiple paths will determine localization patterns and decipher whether the network should be divided into a set of weakly coupled subnetworks. It is posited that a key factor in understanding post-transcriptional regulation lies in its coupling to the transcriptional regulation network. A data-driven mathematical model that combines transcriptional and post-transcriptional regulations as a mixed network of directed (transcription) and bidirectional (post-transcription) links will be built. This project is being jointly supported by the Physics of Living Systems program in the Division of Physics and the Systems and Synthetic Biology and Genetic Mechanisms Clusters 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.
转录是蛋白质合成的第一步,包括将DNA序列复制成RNA序列。除了基因表达的转录调节外,还存在一个调节层,称为转录后调节。在真核生物中,微小RNA(miRNAs)是这种调控网络的关键介质。转录后调控仍然知之甚少,许多基本问题仍然悬而未决。基于miRNA的调控的一些特征使其与其他基因调控机制不同:它是化学计量的,因此出现竞争效应,它发生在细胞质中,并且它涉及调节剂和靶标的运输。该项目的目标是了解跨时空尺度的转录后调控所产生的细胞特性,从单个分子的运动和相互作用到网络水平。该项目将支持一个外展计划在韦伯中学柯林斯堡,CO.研究经验,为学生将制定协调与学校教师和整合在一个既定的特殊计划,即韦伯的航空航天教育风险投资(波),为学生提供一个引人入胜的,具有挑战性的,和严格的经验,模拟如何组织和进行外行星探索,鼓励学生追求空间科学研究和未来的职业生涯在行业内的目标。与学校教师的合作将为WAVE课程带来宝贵的创新。主要活动将集中在使用RNA和DNA的生物标志物测试生命的存在,参加单分子RNA跟踪的演示,并评估活细胞中的运动RNA。这个项目的目标是(i)剖析复杂的细胞环境对转录后调控的影响,(ii)阐明转录后网络的串扰效应。PI将使用光学成像在活细胞中的单分子水平上跟踪miRNA和mRNA的路径。实验轨迹将使用理论和计算方法进行分析,包括第一次通过过程和反常扩散理论的动力学速率系数的计算。这些系数将用于数学模型。多路径的分析将确定定位模式,并破译网络是否应该被划分为一组弱耦合的子网。据推测,理解转录后调控的一个关键因素在于它与转录调控网络的耦合。将建立一个数据驱动的数学模型,该模型将转录和转录后调控结合为定向(转录)和双向(转录后)链接的混合网络。该项目由物理学和分子与细胞生物科学部的系统和合成生物学和遗传机制集群的生命系统物理学项目共同支持。该奖项反映了NSF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(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)
Data in: Aging power spectrum of membrane protein transport and other subordinated random walks
数据来源:膜蛋白转运和其他从属随机游走的老化功率谱
  • DOI:
    10.5281/zenodo.5528300
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    0
  • 作者:
    R., Zachary Fox;Barkai, Eli;Krapf, Diego
  • 通讯作者:
    Krapf, Diego
{{ 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 }}

Diego Krapf其他文献

A versatile kinase mobility shift assay (KiMSA) for PKA analysis and cyclic AMP detection in sperm physiology (and beyond)
用于精子生理学(及其他领域)PKA 分析和环 AMP 检测的多功能激酶迁移率变化测定 (KiMSA)
  • DOI:
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    5.5
  • 作者:
    Analia G. Novero;Catalina Curcio;Tomás J Steeman;Andres Binolfi;Diego Krapf;M. Buffone;D. Krapf;Cintia Stival
  • 通讯作者:
    Cintia Stival
Measuring the Binding Energy between Cargo and Forming Clathrin Coated Pits
  • DOI:
    10.1016/j.bpj.2012.11.3426
  • 发表时间:
    2013-01-29
  • 期刊:
  • 影响因子:
  • 作者:
    Aubrey V. Weigel;Michael M. Tamkun;Diego Krapf
  • 通讯作者:
    Diego Krapf
Endoplasmic Reticulum/Plasma Membrane Junctions Function as Membrane Protein Trafficking Hubs
  • DOI:
    10.1016/j.bpj.2012.11.3428
  • 发表时间:
    2013-01-29
  • 期刊:
  • 影响因子:
  • 作者:
    Philip D. Fox;Christpher J. Haberkorn;Aubrey V. Weigel;Elizabeth J. Akin;Matthew J. Kennedy;Diego Krapf;Michael M. Tamkun
  • 通讯作者:
    Michael M. Tamkun
Single Molecule Kv2.1 Channel Dynamics in Live Mammalian Cells
  • DOI:
    10.1016/j.bpj.2009.12.2348
  • 发表时间:
    2010-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    Aubrey V. Weigel;Michael M. Tamkun;Diego Krapf
  • 通讯作者:
    Diego Krapf
Neuronal KV2.1 Clusters Influence the Diffusion Landscape of the Adjacent Astrocyte Membrane
  • DOI:
    10.1016/j.bpj.2017.11.437
  • 发表时间:
    2018-02-02
  • 期刊:
  • 影响因子:
  • 作者:
    Ashley N. Leek;Diego Krapf;Michael Tamkun
  • 通讯作者:
    Michael Tamkun

Diego Krapf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('Diego Krapf', 18)}}的其他基金

Structure and Functions of ER/Plasma Membrane Junctions
内质网/质膜连接的结构和功能
  • 批准号:
    1401432
  • 财政年份:
    2014
  • 资助金额:
    $ 54万
  • 项目类别:
    Continuing Grant
Membrane Dynamics Underlying Kv2.1 Cluster Formation
Kv2.1 团簇形成背后的膜动力学
  • 批准号:
    0956714
  • 财政年份:
    2010
  • 资助金额:
    $ 54万
  • 项目类别:
    Continuing Grant

相似国自然基金

枯草芽孢杆菌BSF01降解高效氯氰菊酯的种内群体感应机制研究
  • 批准号:
    31871988
  • 批准年份:
    2018
  • 资助金额:
    59.0 万元
  • 项目类别:
    面上项目
基于掺硼直拉单晶硅片的Al-BSF和PERC太阳电池光衰及其抑制的基础研究
  • 批准号:
    61774171
  • 批准年份:
    2017
  • 资助金额:
    63.0 万元
  • 项目类别:
    面上项目
B细胞刺激因子-2(BSF-2)与自身免疫病的关系
  • 批准号:
    38870708
  • 批准年份:
    1988
  • 资助金额:
    3.0 万元
  • 项目类别:
    面上项目

相似海外基金

NSF-BSF: Many-Body Physics of Quantum Computation
NSF-BSF:量子计算的多体物理学
  • 批准号:
    2338819
  • 财政年份:
    2024
  • 资助金额:
    $ 54万
  • 项目类别:
    Continuing 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:
    $ 54万
  • 项目类别:
    Standard Grant
Collaborative Research: NSF-BSF: Under Pressure: The evolution of guard cell turgor and the rise of the angiosperms
合作研究:NSF-BSF:压力之下:保卫细胞膨压的进化和被子植物的兴起
  • 批准号:
    2333889
  • 财政年份:
    2024
  • 资助金额:
    $ 54万
  • 项目类别:
    Standard Grant
Collaborative Research: NSF-BSF: Under Pressure: The evolution of guard cell turgor and the rise of the angiosperms
合作研究:NSF-BSF:压力之下:保卫细胞膨压的进化和被子植物的兴起
  • 批准号:
    2333888
  • 财政年份:
    2024
  • 资助金额:
    $ 54万
  • 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:
    2321481
  • 财政年份:
    2024
  • 资助金额:
    $ 54万
  • 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:
    $ 54万
  • 项目类别:
    Continuing Grant
NSF-BSF: Collaborative Research: Solids and reactive transport processes in sewer systems of the future: modeling and experimental investigation
NSF-BSF:合作研究:未来下水道系统中的固体和反应性输送过程:建模和实验研究
  • 批准号:
    2134594
  • 财政年份:
    2024
  • 资助金额:
    $ 54万
  • 项目类别:
    Standard Grant
NSF-BSF Combinatorial Set Theory and PCF
NSF-BSF 组合集合论和 PCF
  • 批准号:
    2400200
  • 财政年份:
    2024
  • 资助金额:
    $ 54万
  • 项目类别:
    Standard Grant
NSF-BSF: CDS&E: Tensor Train methods for Quantum Impurity Solvers
NSF-BSF:CDS
  • 批准号:
    2401159
  • 财政年份:
    2024
  • 资助金额:
    $ 54万
  • 项目类别:
    Continuing Grant
NSF-BSF: Collaborative Research: AF: Small: Algorithmic Performance through History Independence
NSF-BSF:协作研究:AF:小型:通过历史独立性实现算法性能
  • 批准号:
    2420942
  • 财政年份:
    2024
  • 资助金额:
    $ 54万
  • 项目类别:
    Standard Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了