Translational control of stress response signaling

应激反应信号的翻译控制

基本信息

  • 批准号:
    10552193
  • 负责人:
  • 金额:
    $ 42.38万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-09-22 至 2028-08-31
  • 项目状态:
    未结题

项目摘要

Project Summary Cellular stress-responsive mechanisms are essential for cells to adapt to various environmental and physiological conditions. The overall goal of the research program is to understand how cells regulate mRNA translation as part of their stress adaptation process. Of particular interest is a pathway referred to as the Integrated Stress Response (ISR), which is initiated by stress-activated eIF2a kinases that respond to several distinct types of stress. Abnormal regulation of ISR is associated with various metabolic and neurodegenerative diseases, including ribosomopathies caused by heterozygosity in ribosome subunit genes and Charcot Marie Tooth Disease caused by certain tRNA synthetase mutations. The ISR signaling mechanism is intriguing because this pathway induces stress-responsive gene transcription, and coincidentally, suppresses general mRNA translation. ISR inhibits mRNA translation at multiple levels, including the specific inhibition of translation initiation factors, eIF2a and eIF-4E. In addition, recent evidence indicates that ribosome stalling on mRNAs is associated with ISR. These observations raise a fundamental question regarding how stress-responsive transcripts overcome these multiple translational blocks, and in some cases, increase their translation as part of ISR signaling. To address this, we propose to use the facile genetic tools of Drosophila. The ISR regulatory mechanisms are conserved in this organism, and there are genetic mutations that serve as models for human diseases with abnormal ISR signaling. Our preliminary genetic screen in Drosophila has identified several poorly characterized translational regulators as factors required for ISR signaling. Building on these observations, we will test the central hypothesis that the newly identified factors specifically mediate the translation of stress-responsive transcripts, thereby helping those mRNAs to bypass translational blocks imposed by ISR. We will further determine the physiological significances of the newly identified translational regulatory mechanisms in the Drosophila models of ribosomopathies and Charcot Marie Tooth Disease. A successful realization of the proposed plan will advance our conceptual understanding of stress-responsive gene expression, and help develop new therapeutic strategies against diseases associated with ISR.
项目总结

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 }}

HYUNG D RYOO其他文献

HYUNG D RYOO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('HYUNG D RYOO', 18)}}的其他基金

Translation control of stress response and innate immunity
应激反应和先天免疫的翻译控制
  • 批准号:
    10004111
  • 财政年份:
    2018
  • 资助金额:
    $ 42.38万
  • 项目类别:
Quality control mechanisms against misfolded rhodopsins in Drosophila.
针对果蝇中错误折叠视紫红质的质量控制机制。
  • 批准号:
    8664498
  • 财政年份:
    2013
  • 资助金额:
    $ 42.38万
  • 项目类别:
Unfolded Protein Response in Eye Development and Disease
眼睛发育和疾病中未折叠的蛋白质反应
  • 批准号:
    9759937
  • 财政年份:
    2010
  • 资助金额:
    $ 42.38万
  • 项目类别:
Quality control mechanisms against misfolded rhodopsins in Drosophila.
针对果蝇中错误折叠视紫红质的质量控制机制。
  • 批准号:
    8113397
  • 财政年份:
    2010
  • 资助金额:
    $ 42.38万
  • 项目类别:
Cellular Response to Misfolded Rhodopsins.
细胞对错误折叠视紫红质的反应。
  • 批准号:
    8757005
  • 财政年份:
    2010
  • 资助金额:
    $ 42.38万
  • 项目类别:
Cellular Response to Misfolded Rhodopsins.
细胞对错误折叠视紫红质的反应。
  • 批准号:
    8901175
  • 财政年份:
    2010
  • 资助金额:
    $ 42.38万
  • 项目类别:
Quality control mechanisms against misfolded rhodopsins in Drosophila.
针对果蝇中错误折叠视紫红质的质量控制机制。
  • 批准号:
    7947938
  • 财政年份:
    2010
  • 资助金额:
    $ 42.38万
  • 项目类别:
Unfolded Protein Response in Drosophila models of Retinitis Pigmentosa
色素性视网膜炎果蝇模型中未折叠的蛋白质反应
  • 批准号:
    10735578
  • 财政年份:
    2010
  • 资助金额:
    $ 42.38万
  • 项目类别:
Unfolded Protein Response in Eye Development and Disease
眼睛发育和疾病中未折叠的蛋白质反应
  • 批准号:
    10171856
  • 财政年份:
    2010
  • 资助金额:
    $ 42.38万
  • 项目类别:
Quality control mechanisms against misfolded rhodopsins in Drosophila.
针对果蝇中错误折叠视紫红质的质量控制机制。
  • 批准号:
    8301711
  • 财政年份:
    2010
  • 资助金额:
    $ 42.38万
  • 项目类别:

相似海外基金

Amino-acyl tRNA synthetases: investigations of tRNA specificity for application in ProxiMAX / synthetic biology.
氨酰 tRNA 合成酶:研究 tRNA 特异性在 ProxiMAX/合成生物学中的应用。
  • 批准号:
    BB/L015633/1
  • 财政年份:
    2014
  • 资助金额:
    $ 42.38万
  • 项目类别:
    Training Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了