Fluorescence lifetime-based single fluorophore biosensors of post-translational modification enzyme activity

基于荧光寿命的翻译后修饰酶活性单荧光团生物传感器

基本信息

  • 批准号:
    9359690
  • 负责人:
  • 金额:
    $ 34.52万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-08-01 至 2020-07-31
  • 项目状态:
    已结题

项目摘要

Despite decades of research on post-translational modification enzymes, little is known about their dynamic, spatiotemporal activities on a subcellular level—and yet the nature of these subcellular activities is often key to understanding their dysfunction in cancer. The goal of this project is to develop a fluorescence lifetime-based technology to map those activities in living cells at subcellular resolution. This approach is based on robust preliminary data in which we demonstrate feasibility for detecting tyrosine kinase activity (an important PTM in many cancers) via highly resolved fluorescence lifetime shifts for three peptide probes (for Abl, Src-family, and Syk kinases), including multiplexed analysis of two probes at a time. In Aim 1, we will fully characterize the physiochemical mechanism that gives rise to the shift, which involves binding of the phosphorylated peptide product of the kinase reaction to an SH2 domain. This will allow us to understand and predict lifetime shift effects, enabling targeted probe design. In Aim 2, we will characterize and further develop the multiplexed analysis of multiple probes, using a biologically relevant model system (the integrin signaling pathway) to validate the utility of the method. In Aim 3, we will broaden the scope of the technology to detect other PTM enzyme activities, starting with Ser/Thr kinases and acetyltransferases. The work described in this proposal will deliver 1) a suite of novel, complementary probes for PTM enzyme function in cells, 2) a strategy to develop additional probes, 3) high-throughput in vitro methods for detecting PTMs via fluorescence lifetime shifts, and 4) cutting edge methods for imaging multiple probes in the same cell. These tools will make unique contributions to the understanding of PTM dynamics in the cell and to the elucidation of roles for subcellular kinase signaling in disease.
尽管对翻译后修饰酶进行了数十年的研究,但对它们的动态,

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 }}

Laurie L. Parker其他文献

Laurie L. Parker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('Laurie L. Parker', 18)}}的其他基金

Multiplexed proteomics-based kinase assay development
基于多重蛋白质组学的激酶测定开发
  • 批准号:
    10810004
  • 财政年份:
    2022
  • 资助金额:
    $ 34.52万
  • 项目类别:
Multiplexed proteomics-based kinase assay development
基于多重蛋白质组学的激酶测定开发
  • 批准号:
    10467462
  • 财政年份:
    2022
  • 资助金额:
    $ 34.52万
  • 项目类别:
Multiplexed proteomics-based kinase assay development
基于多重蛋白质组学的激酶测定开发
  • 批准号:
    10615893
  • 财政年份:
    2022
  • 资助金额:
    $ 34.52万
  • 项目类别:
Multiplexed proteomics-based kinase assay development
基于多重蛋白质组学的激酶测定开发
  • 批准号:
    10793244
  • 财政年份:
    2022
  • 资助金额:
    $ 34.52万
  • 项目类别:
High-Throughput Screening Platform for Cancer Drug Discovery
癌症药物发现的高通量筛选平台
  • 批准号:
    10432025
  • 财政年份:
    2020
  • 资助金额:
    $ 34.52万
  • 项目类别:
High-Throughput Screening Platform for Cancer Drug Discovery
癌症药物发现的高通量筛选平台
  • 批准号:
    10163816
  • 财政年份:
    2020
  • 资助金额:
    $ 34.52万
  • 项目类别:
Biosensor Assay to Screen for Signaling Pathway Inhibition in Cancer
用于筛选癌症信号通路抑制的生物传感器测定
  • 批准号:
    9445128
  • 财政年份:
    2017
  • 资助金额:
    $ 34.52万
  • 项目类别:
Biosensor Assay to Screen for Signaling Pathway Inhibition in Cancer
用于筛选癌症信号通路抑制的生物传感器测定
  • 批准号:
    8956420
  • 财政年份:
    2014
  • 资助金额:
    $ 34.52万
  • 项目类别:
Biosensor Assay to Screen for Signaling Pathway Inhibition in Cancer
用于筛选癌症信号通路抑制的生物传感器测定
  • 批准号:
    9076374
  • 财政年份:
    2014
  • 资助金额:
    $ 34.52万
  • 项目类别:
Multiplexed Kinase Biosensor Technology to Detect Leukemia Signaling with Mass Sp
多重激酶生物传感器技术通过 Mass Sp 检测白血病信号传导
  • 批准号:
    8930087
  • 财政年份:
    2014
  • 资助金额:
    $ 34.52万
  • 项目类别:

相似海外基金

ADVANCED DEVELOPMENT OF LQ A LIPOSOME-BASED SAPONIN-CONTAINING ADJUVANT FOR USE IN PANSARBECOVIRUS VACCINES
用于 Pansarbecovirus 疫苗的 LQ A 脂质体含皂苷佐剂的先进开发
  • 批准号:
    10935820
  • 财政年份:
    2023
  • 资助金额:
    $ 34.52万
  • 项目类别:
ADVANCED DEVELOPMENT OF BBT-059 AS A RADIATION MEDICAL COUNTERMEASURE FOR DOSING UP TO 48H POST EXPOSURE"
BBT-059 的先进开发,作为辐射医学对策,可在暴露后 48 小时内进行给药”
  • 批准号:
    10932514
  • 财政年份:
    2023
  • 资助金额:
    $ 34.52万
  • 项目类别:
Advanced Development of a Combined Shigella-ETEC Vaccine
志贺氏菌-ETEC 联合疫苗的先进开发
  • 批准号:
    10704845
  • 财政年份:
    2023
  • 资助金额:
    $ 34.52万
  • 项目类别:
Advanced development of composite gene delivery and CAR engineering systems
复合基因递送和CAR工程系统的先进开发
  • 批准号:
    10709085
  • 财政年份:
    2023
  • 资助金额:
    $ 34.52万
  • 项目类别:
Advanced Development of Gemini-DHAP
Gemini-DHAP的高级开发
  • 批准号:
    10760050
  • 财政年份:
    2023
  • 资助金额:
    $ 34.52万
  • 项目类别:
Advanced development and validation of an in vitro platform to phenotype brain metastatic tumor cells using artificial intelligence
使用人工智能对脑转移肿瘤细胞进行表型分析的体外平台的高级开发和验证
  • 批准号:
    10409385
  • 财政年份:
    2022
  • 资助金额:
    $ 34.52万
  • 项目类别:
ADVANCED DEVELOPMENT OF A VACCINE FOR PANDEMIC AND PRE-EMERGENT CORONAVIRUSES
针对大流行和突发冠状病毒的疫苗的高级开发
  • 批准号:
    10710595
  • 财政年份:
    2022
  • 资助金额:
    $ 34.52万
  • 项目类别:
Advanced development and validation of an in vitro platform to phenotype brain metastatic tumor cells using artificial intelligence
使用人工智能对脑转移肿瘤细胞进行表型分析的体外平台的高级开发和验证
  • 批准号:
    10630975
  • 财政年份:
    2022
  • 资助金额:
    $ 34.52万
  • 项目类别:
ADVANCED DEVELOPMENT OF A VACCINE CANDIDATE FOR STAPHYLOCOCCUS AUREUS INFECTION
金黄色葡萄球菌感染候选疫苗的高级开发
  • 批准号:
    10710588
  • 财政年份:
    2022
  • 资助金额:
    $ 34.52万
  • 项目类别:
ADVANCED DEVELOPMENT OF A VACCINE FOR PANDEMIC AND PRE-EMERGENT CORONAVIRUSES
针对大流行和突发冠状病毒的疫苗的高级开发
  • 批准号:
    10788051
  • 财政年份:
    2022
  • 资助金额:
    $ 34.52万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了