Collaborative Proposal: Role of tRNA base modifications in genetic code accuracy and cellular fitness

合作提案:tRNA 碱基修饰在遗传密码准确性和细胞适应性中的作用

基本信息

  • 批准号:
    1818131
  • 负责人:
  • 金额:
    $ 45.49万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-08-01 至 2023-07-31
  • 项目状态:
    已结题

项目摘要

Organisms are presumed to maintain a high accuracy of translation to ensure that little variation occurs in the sequences of proteins involved in essential cellular functions. However, a relaxed translational stringency has recently been observed across all branches of life, suggesting that under certain circumstances organisms may tolerate higher translation error rates than previously estimated. Indeed, a decrease in translation stringency has the potential to yield new proteins that provide short- or long-term survival benefits. The overall objective of this project is to understand the connections between tRNA base modifications, changes in translation accuracy and cellular fitness. Graduate and undergraduate students will receive interdisciplinary training through their work on this project. An evolution-in-action module (EvolvingSTEM) has been implemented in New Hampshire and Pennsylvania high schools and will be introduced to biology students in two Winston-Salem, North Carolina public high schools.This project will test the hypothesis that modification of the tRNA wobble base is a tunable component of translation rather than a toggle switch that when turned off leads to error catastrophe. This proposal has three objectives. Molecular dynamics and enzyme kinetics approaches will be used to characterize evolved BcTilS:tRNAIle2 variants in vitro and in silico in order to understand the catalytic and conformational changes that occur in these variants. The in vivo effects of TilS:tRNAIle2 dysfunction such as which amino acid is inserted at AUA codons, which amino acid is present at the 3'-end of tRNAIle2, and what is the metabolic mechanism of enhanced fitness will be investigated. Finally, noncanonical cellular partners of TilS and tRNAIle2 that may play alternative or additional roles in enhanced bacterial fitness will be identified.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.
假定生物体保持高翻译准确性,以确保参与基本细胞功能的蛋白质序列几乎不发生变化。 然而,最近在生命的所有分支中都观察到了宽松的翻译严格性,这表明在某些情况下,生物体可能容忍比以前估计的更高的翻译错误率。 事实上,翻译严格性的降低有可能产生提供短期或长期生存益处的新蛋白质。 该项目的总体目标是了解tRNA碱基修饰、翻译准确性变化和细胞适应性之间的联系。 研究生和本科生将通过他们在这个项目上的工作接受跨学科的培训。 在行动中的进化模块(EvolvingSTEM)已在新罕布什尔州和宾夕法尼亚州的高中实施,并将介绍给生物学生在两个温斯顿-塞勒姆,北卡罗来纳州公立高中,这个项目将测试的假设,修改的tRNA摆动基地是一个可调的组成部分翻译,而不是一个切换开关,当关闭时,导致错误的灾难。这项建议有三个目标。 分子动力学和酶动力学方法将用于表征进化的BcTilS:tRNAIle2变体在体外和计算机模拟,以了解这些变体中发生的催化和构象变化。 将研究TilS:tRNAIle2功能障碍的体内效果,例如在AUA密码子处插入哪个氨基酸,在tRNAIle2的3 '端存在哪个氨基酸,以及增强适应性的代谢机制是什么。 最后,TilS和tRNAIle2的非典型细胞合作伙伴,可能发挥替代或额外的作用,在增强细菌fitness将被identified.This奖项反映了NSF的法定使命,并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

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)
Bacterial wobble modifications of NNA‐decoding tRNAs
NNA 的细菌摆动修饰——解码 tRNA
  • DOI:
    10.1002/iub.2120
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    4.6
  • 作者:
    Nilsson, Emil M.;Alexander, Rebecca W.
  • 通讯作者:
    Alexander, Rebecca W.
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Rebecca Alexander其他文献

The Foldings of a Square to Convex Polyhedra
正方形到凸多面体的折叠
  • DOI:
    10.1007/978-3-540-44400-8_5
  • 发表时间:
    2002
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Rebecca Alexander;H. Dyson;J. O'Rourke
  • 通讯作者:
    J. O'Rourke
Interatomic potentials for irradiation-induced defects in iron
铁中辐照诱导缺陷的原子间势
  • DOI:
    10.1016/j.jnucmat.2020.152141
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    3.1
  • 作者:
    Rebecca Alexander;L. Proville;C. Becquart;Alexandra M. Goryeava;J. Dérès;Clovis Lapointe;M. Marinica
  • 通讯作者:
    M. Marinica
Sex Differences in the Use of Delayed Semantic Context When Listening to Disrupted Speech
听中断语音时使用延迟语义上下文的性别差异
  • DOI:
  • 发表时间:
    2012
  • 期刊:
  • 影响因子:
    3.8
  • 作者:
    J. Liederman;Janet McGraw Fisher;Alexis Coty;Geetha Matthews;R. Frye;Alexis Lincoln;Rebecca Alexander
  • 通讯作者:
    Rebecca Alexander
Evaluating suicide attitudes and suicide literacy in adolescents.
评估青少年的自杀态度和自杀素养。
  • DOI:
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    3.3
  • 作者:
    A. Calear;A. Morse;H. Christensen;S. McCallum;A. Werner;Rebecca Alexander;P. Batterham
  • 通讯作者:
    P. Batterham
Policing the police service
维持警察服务

Rebecca Alexander的其他文献

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{{ truncateString('Rebecca Alexander', 18)}}的其他基金

Dissecting Catalytic Features of Diverse Methionyl-tRNA Synthetase Enzymes
剖析多种甲硫氨酰-tRNA 合成酶的催化特性
  • 批准号:
    1052402
  • 财政年份:
    2011
  • 资助金额:
    $ 45.49万
  • 项目类别:
    Continuing Grant
CAREER: Dissecting Inter-domain Communication in Methionyl-tRNA Synthetase
职业:剖析甲硫氨酰-tRNA 合成酶的域间通讯
  • 批准号:
    0448243
  • 财政年份:
    2005
  • 资助金额:
    $ 45.49万
  • 项目类别:
    Continuing Grant
Acquisition of a Chemistry/Biology Biomolecular Imaging Center
收购化学/生物学生物分子成像中心
  • 批准号:
    0320801
  • 财政年份:
    2003
  • 资助金额:
    $ 45.49万
  • 项目类别:
    Standard Grant

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