Elucidating the novel mechanism of importins in NLRP6 inflammasome regulation

阐明NLRP6炎症小体调节中输入蛋白的新机制

基本信息

  • 批准号:
    10574850
  • 负责人:
  • 金额:
    $ 23.33万
  • 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:
    2023-08-10 至 2025-07-31
  • 项目状态:
    未结题

项目摘要

Abstract Inflammasomes are multi-protein signaling scaffolds that form in the cytosol upon stimulation by pathogen and damage signals to activate caspase-1. Canonical inflammasome sensors are mainly nucleotide-binding domain (NBD) and leucine-rich repeat containing (NLR) proteins, such as NLRP1, NLRP3 and NLRP6. Once inflammasome is activated, caspase-1 is recruited to the platform and activated through proximity-induced autoproteolysis. Activated caspase-1 processes pro-interleukin (IL)-1b, pro-IL-18, and the pore-forming protein gasdermin D (GSDMD), resulting in the maturation and release of these cytokines, as well as pyroptotic cell death. NLRP6 plays versatile roles in host defense. It is highly expressed in the intestine and the liver. The inflammasome function of NLRP6 has been reported to protect the host from pathogen evasion and injury-induced tissue damage. On the other hand, the excessive NLRP6 inflammasome activation and the subsequent hyperactive IL-18 signaling may exacerbate the tissue damage and cause chronic inflammatory diseases such as inflammatory bowel disease (IBD). Whether there is an intrinsic cellular signal that tunes the activity of NLRP6 inflammasome becomes an intriguing question. The question is critical to understanding how our body maintains tissue homeostasis by harnessing this important inflammasome and to provide targeted therapy for certain diseases. Nuclear import is an essential cellular process in innate immune defense by translocating activated transcription factors into the nucleus for interferon production. Plant NLRs themselves have been reported to enable host defense through pathogen effector-mediated nuclear translocation. In our preliminary study, we found that importin-b1, a common nuclear import receptor, inhibits dsRNA-induced liquid-liquid phase separation of NLRP6 in-vitro, which implicates the potential link between nuclear import and NLRP6 inflammasome signaling. In this application, we will investigate the potential role of importins in regulating the NLRP6 inflammasome by tackling two questions: 1) molecular basis of the importin-NLRP6 interaction (cryo-electron microscopy and biochemistry), and 2) the roles of importin-b1 in negatively regulating NLRP6 inflammasome upon viral infection (inflammasome cell biology).
摘要

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 }}

Chen Shen其他文献

Chen Shen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 }}

相似海外基金

RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 23.33万
  • 项目类别:
    Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 23.33万
  • 项目类别:
    Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 23.33万
  • 项目类别:
    Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 23.33万
  • 项目类别:
    Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 23.33万
  • 项目类别:
    Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 23.33万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 23.33万
  • 项目类别:
    Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
  • 批准号:
    2301846
  • 财政年份:
    2023
  • 资助金额:
    $ 23.33万
  • 项目类别:
    Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 23.33万
  • 项目类别:
    Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
  • 批准号:
    23K16076
  • 财政年份:
    2023
  • 资助金额:
    $ 23.33万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了