Functional mechanisms and therapeutic potential of EAG channel regulators

EAG通道调节剂的功能机制和治疗潜力

基本信息

  • 批准号:
    10593928
  • 负责人:
  • 金额:
    $ 60.31万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-04-15 至 2026-03-31
  • 项目状态:
    未结题

项目摘要

Ether-a-go-go (EAG) potassium selective channels are important regulators of neuronal excitability and cancer progression. Defects in EAG channel function are associated with neurological disorders and cancer. Despite the physiological importance of EAG channels, molecular mechanisms of EAG channel regulation by intracellular ligands and clinically relevant EAG channel regulators are not known. The goal of this proposal is to uncover molecular mechanisms of EAG channel regulation by intracellular ligands recently discovered by our laboratory and to determine a therapeutic potential of these ligands for treatment of diseases linked to EAG channels. In Specific Aim 1 we plan to solve X-ray structures of the intracellular Per-Arnt-Sim (PAS) and cyclic nucleotide- binding homology (CNBH) domains of EAG channels bound to the recently identified ligands and conduct computational simulations of the ligand binding to the PAS and CNBH domains to uncover the structural basis of EAG channel regulation by the intracellular ligands. The structural findings will be then used as a road map to guide functional experiments on the molecular mechanisms of EAG channel regulation by the ligands. In Specific Aim 2 we plan to use surface plasmon resonance method to identify novel EAG channel ligands that affect channel function through PAS and CNBH domain interface. We will then use electrophysiology to determine functional implications of strengthening or weakening of the PAS/CNBH domain interface by the identified regulators on the function of EAG channels. In Specific Aim 3 we plan to use tissue culture and zebrafish xenograft models to test therapeutic potential of the identified regulators for treatment of cancer. The results of these studies will be crucial for understanding fundamental regulatory mechanisms of EAG and related ERG and ELK channels, and for attaining therapeutic potential of EAG channel regulators.
乙醚-a-go-go(EAG)钾选择通道是神经元的重要调节器 兴奋性和癌症进展。与EAG渠道功能缺陷有关 患有神经系统疾病和癌症。尽管EAG在生理上很重要 细胞内配体对EAG通道的调控及其分子机制 临床相关的EAG经络调节剂尚不为人所知。这项提议的目标是 揭示细胞内配体调节EAG通道的分子机制 最近由我们实验室发现,并确定这些药物的治疗潜力 配基用于治疗与EAG经络有关的疾病。在具体目标1中,我们计划 解决细胞内Per-Arnt-Sim(PAS)和环核苷酸的X射线结构- 与新近鉴定的EAG通道结合的同源结构域 并对配体与Pas和Pas的结合进行计算模拟 CNBH结构域揭示EAG通道调控的结构基础 细胞内的配体。然后,结构发现将被用作路线图以指导 三七总皂甙调节EAG通道分子机制的功能实验 配基。在具体目标2中,我们计划使用表面等离子体共振方法来识别 通过PAS和CNBH结构域影响通道功能的新型EAG通道配体 界面。然后,我们将使用电生理学来确定 被识别的PAS/CNBH结构域界面的加强或减弱 监管者对EAG渠道的作用。在特定的目标3中,我们计划使用纸巾 培养和斑马鱼异种移植模型测试已鉴定的 癌症治疗的监管机构。这些研究的结果将对 理解EAG及相关视网膜色素蛋白和麋鹿的基本调控机制 为实现EAG经络调节剂的治疗潜力。

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 }}

Tinatin I Brelidze其他文献

Tinatin I Brelidze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('Tinatin I Brelidze', 18)}}的其他基金

Functional mechanisms and therapeutic potential of EAG channel regulators
EAG通道调节剂的功能机制和治疗潜力
  • 批准号:
    10393686
  • 财政年份:
    2021
  • 资助金额:
    $ 60.31万
  • 项目类别:
Functional mechanisms and therapeutic potential of EAG channel regulators
EAG通道调节剂的功能机制和治疗潜力
  • 批准号:
    10231407
  • 财政年份:
    2021
  • 资助金额:
    $ 60.31万
  • 项目类别:
KCNH channel regulation by intracellular ligands
细胞内配体对 KCNH 通道的调节
  • 批准号:
    10372601
  • 财政年份:
    2018
  • 资助金额:
    $ 60.31万
  • 项目类别:
KCNH channel regulation by intracellular ligands
细胞内配体对 KCNH 通道的调节
  • 批准号:
    10581873
  • 财政年份:
    2018
  • 资助金额:
    $ 60.31万
  • 项目类别:
KCNH channel regulation by intracellular ligands
细胞内配体对 KCNH 通道的调节
  • 批准号:
    10375400
  • 财政年份:
    2018
  • 资助金额:
    $ 60.31万
  • 项目类别:
KCNH channel regulation by intracellular ligands
细胞内配体对 KCNH 通道的调节
  • 批准号:
    9896844
  • 财政年份:
    2018
  • 资助金额:
    $ 60.31万
  • 项目类别:

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:
    $ 60.31万
  • 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:
    $ 60.31万
  • 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:
    $ 60.31万
  • 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:
    $ 60.31万
  • 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:
    $ 60.31万
  • 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:
    $ 60.31万
  • 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:
    $ 60.31万
  • 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:
    $ 60.31万
  • 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:
    $ 60.31万
  • 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:
    $ 60.31万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了