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

基本信息

项目摘要

PROJECT SUMMARY/ABSTRACT Single-cell technologies have become the cornerstone of biomedical and cell biology research. Next- generation sequencing-based technologies have enabled large-scale characterization of transcript expressions in single cells from clinical specimens and reveal unexpected cellular heterogeneity related to pathogenesis. However, many integrative studies have shown only low to moderate correlations between the abundance of RNA transcripts and their corresponding proteins, the main determinants of cell phenotype. We hypothesize mass spectrometry-based single-cell proteomics could provide direct insight on the cellular heterogeneity and inform protein markers related to disease progression and resistance to therapy. The overall objective of this project is to develop a high throughput single-cell proteomics (scProteomics) platform to enable the routine analysis of >10,000 single cells at a depth of 2000 proteins in a cost-efficient way. The developed technology will be disseminated to the research community through close collaboration with a commercial partner. We will also apply scProteomics to interrogate the heterogeneity of both malignant plasma cell and immune cell populations from multiple myeloma patients. We will pursue these goals through three specific aims: 1) To establish an ultra-high throughput single-cell preparation method by coupling an enhanced multiplexing method with high-density nested nanoPOTS chips and multi-channel droplet dispensing system; We aim to process >2000 cells in a single microchip, and multiplex-label 36 single cells for a single LC-MS analysis; 2) To advance the throughput, sensitivity, and quantitation accuracy of LC-MS system. A dual-column nanoLC system and a FAIMS-based MS acquisition method will be developed to enable the analysis of >860 cells per day with high quantitation precision; 3) To apply scProteomics to profile ~10,000 plasma and immune cells from MM patients. We will integrate scProteomics with existing scRNA-seq data to explore tumor heterogeneity, chimeric antigen receptor T-cells (CAR-T) markers, and the immune microenvironment in multiple myeloma. This research is highly innovative because the proposed single-cell proteomics platform will be the first of its kind to routinely and reliably characterize > 10,000 single cells at a throughput comparable to single-cell transcriptomics. It is also the first scProteomics study of primary liquid tumor cells isolated from the pathological environment, e.g. bone marrow of MM patients. Statement of Impact: Tumor heterogeneity has indispensable implications in cancer evolution, tumoral spatial organization, and clinical treatment. Single-cell proteomics could provide a basis to unravel these complicated relationships and to clarify the mechanisms of cancer progression and subclone resistance to therapeutic treatments.
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 }}

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

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:
    $ 64.75万
  • 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:
    $ 64.75万
  • 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:
    10687330
  • 财政年份:
    2020
  • 资助金额:
    $ 64.75万
  • 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:
    $ 64.75万
  • 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:
    $ 64.75万
  • 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:
    $ 64.75万
  • 项目类别:

相似海外基金

CAREER: Efficient Algorithms for Modern Computer Architecture
职业:现代计算机架构的高效算法
  • 批准号:
    2339310
  • 财政年份:
    2024
  • 资助金额:
    $ 64.75万
  • 项目类别:
    Continuing Grant
Hardware-aware Network Architecture Search under ML Training workloads
ML 训练工作负载下的硬件感知网络架构搜索
  • 批准号:
    2904511
  • 财政年份:
    2024
  • 资助金额:
    $ 64.75万
  • 项目类别:
    Studentship
CAREER: Creating Tough, Sustainable Materials Using Fracture Size-Effects and Architecture
职业:利用断裂尺寸效应和架构创造坚韧、可持续的材料
  • 批准号:
    2339197
  • 财政年份:
    2024
  • 资助金额:
    $ 64.75万
  • 项目类别:
    Standard Grant
Travel: Student Travel Support for the 51st International Symposium on Computer Architecture (ISCA)
旅行:第 51 届计算机体系结构国际研讨会 (ISCA) 的学生旅行支持
  • 批准号:
    2409279
  • 财政年份:
    2024
  • 资助金额:
    $ 64.75万
  • 项目类别:
    Standard Grant
Understanding Architecture Hierarchy of Polymer Networks to Control Mechanical Responses
了解聚合物网络的架构层次结构以控制机械响应
  • 批准号:
    2419386
  • 财政年份:
    2024
  • 资助金额:
    $ 64.75万
  • 项目类别:
    Standard Grant
I-Corps: Highly Scalable Differential Power Processing Architecture
I-Corps:高度可扩展的差分电源处理架构
  • 批准号:
    2348571
  • 财政年份:
    2024
  • 资助金额:
    $ 64.75万
  • 项目类别:
    Standard Grant
Collaborative Research: Merging Human Creativity with Computational Intelligence for the Design of Next Generation Responsive Architecture
协作研究:将人类创造力与计算智能相结合,设计下一代响应式架构
  • 批准号:
    2329759
  • 财政年份:
    2024
  • 资助金额:
    $ 64.75万
  • 项目类别:
    Standard Grant
The architecture and evolution of host control in a microbial symbiosis
微生物共生中宿主控制的结构和进化
  • 批准号:
    BB/X014657/1
  • 财政年份:
    2024
  • 资助金额:
    $ 64.75万
  • 项目类别:
    Research Grant
RACCTURK: Rock-cut Architecture and Christian Communities in Turkey, from Antiquity to 1923
RACCTURK:土耳其的岩石建筑和基督教社区,从古代到 1923 年
  • 批准号:
    EP/Y028120/1
  • 财政年份:
    2024
  • 资助金额:
    $ 64.75万
  • 项目类别:
    Fellowship
NSF Convergence Accelerator Track M: Bio-Inspired Surface Design for High Performance Mechanical Tracking Solar Collection Skins in Architecture
NSF Convergence Accelerator Track M:建筑中高性能机械跟踪太阳能收集表皮的仿生表面设计
  • 批准号:
    2344424
  • 财政年份:
    2024
  • 资助金额:
    $ 64.75万
  • 项目类别:
    Standard Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了