New mechanisms of SERCA regulation: Dimerization and Micropeptides

SERCA调控新机制:二聚化和微肽

基本信息

  • 批准号:
    10318147
  • 负责人:
  • 金额:
    $ 57.93万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-01-01 至 2024-11-30
  • 项目状态:
    已结题

项目摘要

Project Summary/Abstract The proposed project uses a two aim strategy to explore molecular mechanisms of the regulation of ion-motive ATPases. Specifically, we will focus on regulation of calcium transporters in skeletal and cardiac muscle. While it is important in all cells, calcium transport plays a particularly critical role in striated muscle, as the uptake of calcium determines the kinetics of muscle relaxation. In the heart, the calcium transport rate also indirectly determines the strength of the cardiac contraction, since it defines the magnitude of the calcium stores and therefore the size of calcium release. Aim 1 of the present proposal focuses on regulation of SERCA by newly discovered species of micropeptides that are related to phospholamban. These new regulators include DWORF, endoregulin, myoregulin, and another-regulin. Little is known about the biophysical determinants of their functional regulation of SERCA. We will quantify the stoichiometry and binding affinity of micropeptide regulatory complexes, the dynamics of regulatory interactions, and the structural determinants of regulation. To quantify these key parameters, we will use several complementary approaches including fluorescence spectroscopy/microscopy, live cell physiological measurements, in vitro functional assays, cryoEM, and NMR. Defining the basic building blocks of micropeptide regulatory complexes is a key step in understanding their biophysical function. Aim 2 will investigate physical and functional coupling of SERCA pumps into dimeric transport complexes. We will investigate the regulation of functional coupling and determine its physiological consequences. In particular, we will test how functional coupling alters SERCA transport rate and the cooperativity of calcium- dependent ATPase activity. The experiments described in the two Aims of this application will provide new insight into fundamental mechanisms of regulation of ion-motive ATPases, and may improve our understanding of the ion transport disorders associated with heart failure. The Principal Investigator has recruited collaborating investigators to provide additional methodological expertise. Calibrated, quantitative calcium uptake measurements will be performed in live cells in the laboratory of Prof. Aleksey Zima, Loyola University Chicago. CryoEM of DWORF-SERCA complexes will be done in the lab of Prof. Howard S. Young, University of Alberta. NMR of DWORF will be done in the lab of Prof. Gianluigi Veglia, University of Minnesota. Each of the collaborators already has a history of productive collaboration with the Principal Investigator. Now they will combine their expertise as a single team to address how micropeptides and SERCA dimerization regulate calcium handling in striated muscle. Additional expertise in molecular biology and animal models of heart failure will be provided by Dr. Toni Pak and Dr. Ivana Kuo, Loyola University Chicago.
项目总结/文摘

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 }}

Seth L Robia其他文献

Seth L Robia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('Seth L Robia', 18)}}的其他基金

New mechanisms of SERCA regulation: Dimerization and Micropeptides
SERCA调控新机制:二聚化和微肽
  • 批准号:
    10063953
  • 财政年份:
    2019
  • 资助金额:
    $ 57.93万
  • 项目类别:
Structure Changes of Ion-motive ATPases
离子动力ATP酶的结构变化
  • 批准号:
    8469347
  • 财政年份:
    2011
  • 资助金额:
    $ 57.93万
  • 项目类别:
Structure Changes of Ion-motive ATPases
离子动力ATP酶的结构变化
  • 批准号:
    8676908
  • 财政年份:
    2011
  • 资助金额:
    $ 57.93万
  • 项目类别:
Structure Changes of Ion-motive ATPases
离子动力ATP酶的结构变化
  • 批准号:
    8187678
  • 财政年份:
    2011
  • 资助金额:
    $ 57.93万
  • 项目类别:
Structure Changes of Ion-motive ATPases
离子动力ATP酶的结构变化
  • 批准号:
    8313896
  • 财政年份:
    2011
  • 资助金额:
    $ 57.93万
  • 项目类别:
Structural Determinants of Calcium Pump Regulation
钙泵调节的结构决定因素
  • 批准号:
    7844209
  • 财政年份:
    2009
  • 资助金额:
    $ 57.93万
  • 项目类别:
Structural Determinants of Calcium Pump Regulation
钙泵调节的结构决定因素
  • 批准号:
    8300136
  • 财政年份:
    2008
  • 资助金额:
    $ 57.93万
  • 项目类别:
Regulatory Interactions of Cardiac Ion Pumps
心脏离子泵的调节相互作用
  • 批准号:
    8893125
  • 财政年份:
    2008
  • 资助金额:
    $ 57.93万
  • 项目类别:
Structural Determinants of Calcium Pump Regulation
钙泵调节的结构决定因素
  • 批准号:
    7645015
  • 财政年份:
    2008
  • 资助金额:
    $ 57.93万
  • 项目类别:
Structural Determinants of Calcium Pump Regulation
钙泵调节的结构决定因素
  • 批准号:
    8103106
  • 财政年份:
    2008
  • 资助金额:
    $ 57.93万
  • 项目类别:

相似海外基金

Acute senescence: a novel host defence counteracting typhoidal Salmonella
急性衰老:对抗伤寒沙门氏菌的新型宿主防御
  • 批准号:
    MR/X02329X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 57.93万
  • 项目类别:
    Fellowship
Transcriptional assessment of haematopoietic differentiation to risk-stratify acute lymphoblastic leukaemia
造血分化的转录评估对急性淋巴细胞白血病的风险分层
  • 批准号:
    MR/Y009568/1
  • 财政年份:
    2024
  • 资助金额:
    $ 57.93万
  • 项目类别:
    Fellowship
Combining two unique AI platforms for the discovery of novel genetic therapeutic targets & preclinical validation of synthetic biomolecules to treat Acute myeloid leukaemia (AML).
结合两个独特的人工智能平台来发现新的基因治疗靶点
  • 批准号:
    10090332
  • 财政年份:
    2024
  • 资助金额:
    $ 57.93万
  • 项目类别:
    Collaborative R&D
Cellular Neuroinflammation in Acute Brain Injury
急性脑损伤中的细胞神经炎症
  • 批准号:
    MR/X021882/1
  • 财政年份:
    2024
  • 资助金额:
    $ 57.93万
  • 项目类别:
    Research Grant
STTR Phase I: Non-invasive focused ultrasound treatment to modulate the immune system for acute and chronic kidney rejection
STTR 第一期:非侵入性聚焦超声治疗调节免疫系统以治疗急性和慢性肾排斥
  • 批准号:
    2312694
  • 财政年份:
    2024
  • 资助金额:
    $ 57.93万
  • 项目类别:
    Standard Grant
Combining Mechanistic Modelling with Machine Learning for Diagnosis of Acute Respiratory Distress Syndrome
机械建模与机器学习相结合诊断急性呼吸窘迫综合征
  • 批准号:
    EP/Y003527/1
  • 财政年份:
    2024
  • 资助金额:
    $ 57.93万
  • 项目类别:
    Research Grant
FITEAML: Functional Interrogation of Transposable Elements in Acute Myeloid Leukaemia
FITEAML:急性髓系白血病转座元件的功能研究
  • 批准号:
    EP/Y030338/1
  • 财政年份:
    2024
  • 资助金额:
    $ 57.93万
  • 项目类别:
    Research Grant
KAT2A PROTACs targetting the differentiation of blasts and leukemic stem cells for the treatment of Acute Myeloid Leukaemia
KAT2A PROTAC 靶向原始细胞和白血病干细胞的分化,用于治疗急性髓系白血病
  • 批准号:
    MR/X029557/1
  • 财政年份:
    2024
  • 资助金额:
    $ 57.93万
  • 项目类别:
    Research Grant
ロボット支援肝切除術は真に低侵襲なのか?acute phaseに着目して
机器人辅助肝切除术真的是微创吗?
  • 批准号:
    24K19395
  • 财政年份:
    2024
  • 资助金额:
    $ 57.93万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Collaborative Research: Changes and Impact of Right Ventricle Viscoelasticity Under Acute Stress and Chronic Pulmonary Hypertension
合作研究:急性应激和慢性肺动脉高压下右心室粘弹性的变化和影响
  • 批准号:
    2244994
  • 财政年份:
    2023
  • 资助金额:
    $ 57.93万
  • 项目类别:
    Standard Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了