Spatially resolved characterization of proteoforms for functional proteomics

功能蛋白质组学蛋白质型的空间分辨表征

基本信息

项目摘要

PROJECT SUMMARY/ABSTARCT Differentiated cells have distinctive patterns of epigenetic marks including various post-translational modifications (PTMs) on histones that may work in concert to control transcriptional programs. Since epigenetic marks are often altered following exposure to environmental toxins and play multiple roles in disease pathogenesis, the ability to measure histones in a tissue and cell context is a major analytical objective and challenge. Mass spectrometry (MS) based proteomics is a powerful tool for characterizing histone alterations in multiplexed and non-targeted fashion. However, conventional bottom-up (i.e. peptide-level) MS cannot provide complete characterization of the stoichiometry and combinations of multiple PTMs, and other combinatorial sources of variation, that collectively make up any single gene's set of proteoforms (i.e. functional units of a proteome). Top-down (i.e. proteoform-level) MS addresses this challenge by omitting the proteolysis and thus allowing access to the functional proteoforms. However, top-down MS suffers from low sensitivity and dynamic range due to challenges in separation and detection of large and low-abundance proteins and laborious purification steps required to achive high proteome coverage. This severely limits our ability to analyze small samples and employ top-down MS to generate proteoform-aware images of tissues required for a deeper understanding of human organ functioning in health and disease. We have recently developed nanodroplet sample preparation (nanoPOTS) for highly sensitive bottom-up proteomics and extended this approach to tissue imaging with 100 µm spatial resolution. Herein, we propose to develop and deploy nanoPOTS-based top-down MS to enable characterization of proteoforms in tissue sections with near single cell resolution. To increase the resolution from thousands of cells to near single cell, we will employ advanced MS imaging (MSI) approaches. MSI data will be cross-referenced with global proteomics data obtained via microscale top-down MS of microdissected tissue regions. The UG3 phase efforts will be focused on histones and kidney as a development platform and leverage a unique combination of microscale top-down LCMS, MSI and novel image processing and visualization tools. In the UH3 phase, we will construct comprehensive proteoform-specific maps of multiple tissue types and facilitate multimodal molecular mapping of specific functional units of the kidney by leveraging the HubMAP Consortium ongoing efforts. Successful completion of this research will allow for comprehensive characterization of the full spectrum of proteoforms in tissues and cells thus addressing an important and under- studied area of biology and critical gap in HuBMAP efforts.
项目总结/ ABSTARCT

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 }}

Ljiljana Pasa-Tolic其他文献

Ljiljana Pasa-Tolic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('Ljiljana Pasa-Tolic', 18)}}的其他基金

Massive single cell proteomics for cancer biology
用于癌症生物学的大规模单细胞蛋白质组学
  • 批准号:
    10707321
  • 财政年份:
    2022
  • 资助金额:
    $ 40万
  • 项目类别:
Spatially-resolved proteome mapping of senescent cells and their tissue microenvironment at single-cell resolution
单细胞分辨率下衰老细胞及其组织微环境的空间分辨蛋白质组图谱
  • 批准号:
    10684865
  • 财政年份:
    2022
  • 资助金额:
    $ 40万
  • 项目类别:
Spatially-resolved proteome mapping of senescent cells and their tissue microenvironment at single-cell resolution
单细胞分辨率下衰老细胞及其组织微环境的空间分辨蛋白质组图谱
  • 批准号:
    10552842
  • 财政年份:
    2022
  • 资助金额:
    $ 40万
  • 项目类别:
Spatially resolved characterization of proteoforms for functional proteomics
功能蛋白质组学蛋白质型的空间分辨表征
  • 批准号:
    10118771
  • 财政年份:
    2020
  • 资助金额:
    $ 40万
  • 项目类别:
Spatially resolved characterization of proteoforms for functional proteomics
功能蛋白质组学蛋白质型的空间分辨表征
  • 批准号:
    10889043
  • 财政年份:
    2020
  • 资助金额:
    $ 40万
  • 项目类别:
Spatially resolved characterization of proteoforms for functional proteomics
功能蛋白质组学蛋白质型的空间分辨表征
  • 批准号:
    10256724
  • 财政年份:
    2020
  • 资助金额:
    $ 40万
  • 项目类别:

相似国自然基金

转录因子BMAL1调控AChE在昼夜节律紊乱致认知损害中的作用及分子机制
  • 批准号:
    2024Y9230
  • 批准年份:
    2024
  • 资助金额:
    15.0 万元
  • 项目类别:
    省市级项目
基于无机基质固定碳点光学探针研究有机磷农药暴露AChE响应的活体测量
  • 批准号:
  • 批准年份:
    2024
  • 资助金额:
    50 万元
  • 项目类别:
    面上项目
基于AChE/NLRP3 靶点研究垂穗石松中抗AD新型黄酮苷 吐星酸酯类成分的发现及作用机制研究
  • 批准号:
    2024JJ8138
  • 批准年份:
    2024
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
基于GSK-3β/AChE双重抑制的抗AD杂交分子的设计、合成及作用机制研究
  • 批准号:
    22367005
  • 批准年份:
    2023
  • 资助金额:
    32 万元
  • 项目类别:
    地区科学基金项目
基于可逆界面传质调控机制的AChE固定化荧光传感器及有机磷农药高灵敏抗干扰速测
  • 批准号:
    32372427
  • 批准年份:
    2023
  • 资助金额:
    50 万元
  • 项目类别:
    面上项目
利用微流体技术合成富缺陷MOFs材料定向捕获AChE酶构筑高性能传感界面
  • 批准号:
    32302225
  • 批准年份:
    2023
  • 资助金额:
    30 万元
  • 项目类别:
    青年科学基金项目
抗基质干扰导向的AChE仿生荧光探针的设计合成及农药残留速测应用
  • 批准号:
  • 批准年份:
    2022
  • 资助金额:
    53 万元
  • 项目类别:
    面上项目
基于高分辨活性轮廓分析的中药AChE/GSK3β双靶点抑制剂高内涵筛选研究
  • 批准号:
  • 批准年份:
    2022
  • 资助金额:
    30 万元
  • 项目类别:
    青年科学基金项目
新型AChE/NLRP3双靶点抑制剂—藤石松中抗AD新颖黄酮苷吐星酸酯类成分的发现及作用机制研究
  • 批准号:
  • 批准年份:
    2022
  • 资助金额:
    33 万元
  • 项目类别:
    地区科学基金项目
基于AchE靶点的苗药三两银抗阿尔兹海默症甾体生物碱类化合物发现与作用机制研究
  • 批准号:
    82260833
  • 批准年份:
    2022
  • 资助金额:
    33 万元
  • 项目类别:
    地区科学基金项目

相似海外基金

AchE阻害活性アルカロイドの骨格生合成酵素の機能解析と改変
具有AchE抑制活性的生物碱骨架生物合成酶的功能分析及修饰
  • 批准号:
    23K24040
  • 财政年份:
    2024
  • 资助金额:
    $ 40万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Research to create homoisoflavonoid analogues with both AChE inhibitory and neurite outgrowth promoting activities.
研究创建具有乙酰胆碱酯酶抑制和神经突生长促进活性的高异黄酮类似物。
  • 批准号:
    22K05458
  • 财政年份:
    2022
  • 资助金额:
    $ 40万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
AchE阻害活性アルカロイドの骨格生合成酵素の機能解析と改変
具有AchE抑制活性的生物碱骨架生物合成酶的功能分析及修饰
  • 批准号:
    22H02777
  • 财政年份:
    2022
  • 资助金额:
    $ 40万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Exploring reversible AChE inhibitors as a treatment for refractory epilepsies
探索可逆的 AChE 抑制剂治疗难治性癫痫
  • 批准号:
    9764633
  • 财政年份:
    2019
  • 资助金额:
    $ 40万
  • 项目类别:
Towards continuous real-time acetylcholine esterase (AChE) monitoring using wearable sensors
使用可穿戴传感器进行连续实时乙酰胆碱酯酶 (AChE) 监测
  • 批准号:
    2520106
  • 财政年份:
    2018
  • 资助金额:
    $ 40万
  • 项目类别:
    Studentship
GCAMP6 mice for determination of mechanisms of chronic muscle ache, pain and fatigue
GCAMP6 小鼠用于确定慢性肌肉疼痛、疼痛和疲劳的机制
  • 批准号:
    9090636
  • 财政年份:
    2016
  • 资助金额:
    $ 40万
  • 项目类别:
GCAMP6 mice for determination of mechanisms of chronic muscle ache, pain and fatigue
GCAMP6 小鼠用于确定慢性肌肉疼痛、疼痛和疲劳的机制
  • 批准号:
    9260952
  • 财政年份:
    2016
  • 资助金额:
    $ 40万
  • 项目类别:
Developing Cholinesterase (AChE) inhibitor screening methods using Nuclear Magnetic Resonance Spectroscopy (NMR)
使用核磁共振波谱 (NMR) 开发胆碱酯酶 (AChE) 抑制剂筛选方法
  • 批准号:
    1667863
  • 财政年份:
    2015
  • 资助金额:
    $ 40万
  • 项目类别:
    Studentship
Accelerated AChE Reactivator Design by Mechanistic Neutron Scattering Studies
通过机械中子散射研究加速乙酰胆碱酯酶再激活器设计
  • 批准号:
    8735548
  • 财政年份:
    2014
  • 资助金额:
    $ 40万
  • 项目类别:
Accelerated AChE Reactivator Design by Mechanistic Neutron Scattering Studies
通过机械中子散射研究加速乙酰胆碱酯酶再激活器设计
  • 批准号:
    9632884
  • 财政年份:
    2014
  • 资助金额:
    $ 40万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了