CAREER: Oligomeric Stoichiometry of Superoxide Dismutase 1 and Neuronal Antioxidant Defense

职业:超氧化物歧化酶 1 的寡聚化学计量和神经元抗氧化防御

基本信息

  • 批准号:
    2237129
  • 负责人:
  • 金额:
    $ 97.9万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Continuing Grant
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-04-15 至 2028-03-31
  • 项目状态:
    未结题

项目摘要

High levels of metabolic activity require neurons to be competent in handling oxidative stress. This project seeks to understand how neurons modulate the assembly of Cu/Zn superoxide dismutase (SOD1), the frontline antioxidant protein, when they encounter environmental oxidative reagents. The results of this project will inform how oxidative stress changes SOD1 structures for neuronal antioxidant defense. In addition, the PI will initiate a new educational program, 'Quantitative Biophysical Comprehension' (QBiC), to teach students how to quantify the structural state of a protein using bio-imaging experiments. Particular emphasis will be placed on working with University of Houston student chapters to effectively broaden the participation of women and underrepresented minorities in STEM. QBiC will provide interdisciplinary training, modernize the chemistry curriculum and contribute to the NSF goal of developing a strong STEM workforce.Modulation of SOD1 oligomeric states plays a critical role in its function and is thus essential to neuronal antioxidant defense; however, its molecular mechanisms are poorly understood due to the lack of proper analytical tools to quantify protein oligomerization in cells. In the first part of this research program, the PI will develop a quantitative single-molecule approach to quantify SOD1 oligomerizations in the nucleus, cytosol, and mitochondria. An in-cell redox sensor will be employed to quantify the subcellular oxidative status, and mass spectrometry will be used to quantify changes in SOD1 posttranslational modifications under various environmental stressors. The success of this work will answer for the first time how SOD1 interactions and oligomeric distribution are finely tuned in neurons in response to environmental stimuli.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.
高水平的代谢活动要求神经元有能力处理氧化应激。该项目旨在了解神经元在遇到环境氧化试剂时如何调节Cu/Zn超氧化物歧化酶(SOD1)的组装,SOD1是一线抗氧化蛋白。该项目的结果将揭示氧化应激如何改变SOD1结构,从而促进神经元抗氧化防御。此外,PI将启动一个新的教育项目“定量生物物理理解”(QBiC),教学生如何利用生物成像实验定量蛋白质的结构状态。将特别强调与休斯顿大学学生分会合作,有效扩大女性和代表性不足的少数族裔在STEM领域的参与。QBiC将提供跨学科培训,使化学课程现代化,并为NSF培养强大的STEM劳动力的目标做出贡献。SOD1寡聚物状态的调节在其功能中起着关键作用,因此对神经元的抗氧化防御至关重要;然而,由于缺乏适当的分析工具来量化细胞中的蛋白质寡聚化,其分子机制知之甚少。在这个研究项目的第一部分,PI将开发一种定量的单分子方法来量化SOD1在细胞核、细胞质和线粒体中的寡聚化。细胞内氧化还原传感器将用于量化亚细胞氧化状态,质谱将用于量化各种环境胁迫下SOD1翻译后修饰的变化。这项工作的成功将首次回答SOD1相互作用和寡聚物分布是如何在响应环境刺激时在神经元中精细调节的。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(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
From Molecules to Classrooms: A Comprehensive Guide to Single-Molecule Localization Microscopy
  • DOI:
    10.1021/acs.jchemed.3c00938
  • 发表时间:
    2024-01-05
  • 期刊:
  • 影响因子:
    3
  • 作者:
    Yan,Guangjie;Zhang,Yuteng;Chen,Tai-Yen
  • 通讯作者:
    Chen,Tai-Yen
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Tai-Yen Chen其他文献

Quantifying the Oligomeric States of Membrane Proteins in Cells through Superresolution Localizations
  • DOI:
    10.1016/j.bpj.2019.11.921
  • 发表时间:
    2020-02-07
  • 期刊:
  • 影响因子:
  • 作者:
    Xihong Xie;Yu-Shan Cheng;Meng-Hsuan Wen;Aparna Calindi;Tai-Yen Chen
  • 通讯作者:
    Tai-Yen Chen

Tai-Yen Chen的其他文献

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