Molecular Atlas of the Cardiac Intercalated Disc

心脏闰盘分子图谱

基本信息

  • 批准号:
    10348937
  • 负责人:
  • 金额:
    $ 99.8万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-01-20 至 2028-12-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY This grant proposes research on the molecular mechanisms that control the electrical activity of adult cardiac ventricular myocytes. Our focus is on the cardiac intercalated disc (ID), a region of the cell recognized as key to excitability and propagation and yet, only partly characterized in terms of its molecular composition, regulation and function. Our objective is to obtain a map of this structure by integrating proximity and visual proteomics, genomics, physiomics and molecule-specific physiology. We will study control hearts as well as those deficient in Plakophilin-2 (PKP2), an ID molecule that when mutated can cause lethal arrhythmias in the young. The ID was first described as an interdigitation of cell membranes at the site of end-end apposition between adult ventricular myocytes, hosting three electron-dense structures: gap junctions, desmosomes and adherens junctions (later redefined as mixed junctions or area composita1). More recent work shows that the ID also hosts protein complexes fundamental to electrophysiology. In fact, more than 70 years since it was described as an electron-dense structure, the ID emerges as a node that congregates the molecular machinery involved in all aspects of electrical activity: excitation, repolarization, propagation and control of Ca2+i. Despite the known importance of the ID in cell function, there is a wide knowledge gap regarding its molecular composition and its varied functional roles. Part of this limitation results from the fact that, as opposed to other membrane-wrapped cell components (e.g., mitochondria), isolation of the ID as a single organelle has not been possible given its complex geometry, and the fact that it is open to the cell interior without a limiting barrier of its own. Here, we circumvent these limitations by combining proximity and visual proteomics. The list of interactors will serve as a platform to query genomics and phenotype data, and to guide molecule-specific studies. Cardiac arrhythmias are common, debilitating and in many cases, fatal. Progress has been made in the development of devices and invasive strategies which, as sophisticated and life-saving as they are, can also cause serious and irreparable damage to the heart. In the context of medical therapy, the field of arrhythmias has been lagging behind others (e.g., cancer therapy), where a deep understanding of molecular components and their interdependence have led to the discovery of chemical agents that can slow down or arrest disease progression. We do not claim that our study can stop arrhythmias. But we do believe that knowledge of the molecular elements involved in rhythm control can lead to better risk assessment, diagnosis, prevention and therapy. The ID is a domain that concentrates multiple rhythm-control molecules and as such, a perfect target for applying proximity-based methods to advance our knowledge on the control of the heart rhythm.
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 }}

Mario Delmar其他文献

Mario Delmar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('Mario Delmar', 18)}}的其他基金

Molecular Atlas of the Cardiac Intercalated Disc
心脏闰盘分子图谱
  • 批准号:
    10553155
  • 财政年份:
    2022
  • 资助金额:
    $ 99.8万
  • 项目类别:
Role of PKP2 in epicardial structure and function
PKP2 在心外膜结构和功能中的作用
  • 批准号:
    9262386
  • 财政年份:
    2016
  • 资助金额:
    $ 99.8万
  • 项目类别:
Role of desmosomes in cardiac electrical function
桥粒在心电功能中的作用
  • 批准号:
    9332423
  • 财政年份:
    2016
  • 资助金额:
    $ 99.8万
  • 项目类别:
Role of Desmosomes in Cardiac Electrical Function
桥粒在心脏电功能中的作用
  • 批准号:
    8762968
  • 财政年份:
    2013
  • 资助金额:
    $ 99.8万
  • 项目类别:
2013 Cardiac Arrhythmia Mechanisms Gordon Research Conference
2013年心律失常机制戈登研究会议
  • 批准号:
    8450492
  • 财政年份:
    2013
  • 资助金额:
    $ 99.8万
  • 项目类别:
Role of Desmosomes in Cardiac Electrical Function
桥粒在心脏电功能中的作用
  • 批准号:
    8209146
  • 财政年份:
    2011
  • 资助金额:
    $ 99.8万
  • 项目类别:
Role of Desmosomes in Cardiac Electrical Function
桥粒在心脏电功能中的作用
  • 批准号:
    8389874
  • 财政年份:
    2011
  • 资助金额:
    $ 99.8万
  • 项目类别:
Role of Desmosomes in Cardiac Electrical Function
桥粒在心脏电功能中的作用
  • 批准号:
    8041749
  • 财政年份:
    2011
  • 资助金额:
    $ 99.8万
  • 项目类别:
Role of Desmosomes in Cardiac Electrical Function
桥粒在心脏电功能中的作用
  • 批准号:
    8586549
  • 财政年份:
    2011
  • 资助金额:
    $ 99.8万
  • 项目类别:
Stem cells and the fibroblast/adipocyte lineage in arrhythmogenic cardiomyopathy
致心律失常性心肌病中的干细胞和成纤维细胞/脂肪细胞谱系
  • 批准号:
    7825971
  • 财政年份:
    2009
  • 资助金额:
    $ 99.8万
  • 项目类别:

相似海外基金

History of Community and Adult Education in Old Coal Mining Area in Northern Kyushu
九州北部老煤矿区社区与成人教育的历史
  • 批准号:
    26780447
  • 财政年份:
    2014
  • 资助金额:
    $ 99.8万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
High Risk Adult Hepatitis B Vaccination Pilot -Program Area 7
高危成人乙型肝炎疫苗接种试点 - 计划领域 7
  • 批准号:
    8506903
  • 财政年份:
    2012
  • 资助金额:
    $ 99.8万
  • 项目类别:
The San Francisco Bay Area Adult Glioma Survival Study
旧金山湾区成人神经胶质瘤生存研究
  • 批准号:
    7253800
  • 财政年份:
    2007
  • 资助金额:
    $ 99.8万
  • 项目类别:
San Francisco Bay area adult glioma survival study
旧金山湾区成人神经胶质瘤生存研究
  • 批准号:
    6686704
  • 财政年份:
    2002
  • 资助金额:
    $ 99.8万
  • 项目类别:
The San Francisco Bay Area Adult Glioma Survival Study
旧金山湾区成人神经胶质瘤生存研究
  • 批准号:
    8258656
  • 财政年份:
  • 资助金额:
    $ 99.8万
  • 项目类别:
San Francisco Bay area adult glioma survival study
旧金山湾区成人神经胶质瘤生存研究
  • 批准号:
    7550487
  • 财政年份:
  • 资助金额:
    $ 99.8万
  • 项目类别:
The San Francisco Bay Area Adult Glioma Survival Study
旧金山湾区成人神经胶质瘤生存研究
  • 批准号:
    8099448
  • 财政年份:
  • 资助金额:
    $ 99.8万
  • 项目类别:
San Francisco Bay area adult glioma survival study
旧金山湾区成人神经胶质瘤生存研究
  • 批准号:
    7550482
  • 财政年份:
  • 资助金额:
    $ 99.8万
  • 项目类别:
The San Francisco Bay Area Adult Glioma Survival Study
旧金山湾区成人神经胶质瘤生存研究
  • 批准号:
    7885642
  • 财政年份:
  • 资助金额:
    $ 99.8万
  • 项目类别:
San Francisco Bay area adult glioma survival study
旧金山湾区成人神经胶质瘤生存研究
  • 批准号:
    7550492
  • 财政年份:
  • 资助金额:
    $ 99.8万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了