Highly multiplexed tissue imaging with high-plex in situ signal amplification

具有高复数原位信号放大功能的高度复用组织成像

基本信息

  • 批准号:
    10718666
  • 负责人:
  • 金额:
    $ 42万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-06-06 至 2028-05-31
  • 项目状态:
    未结题

项目摘要

Project Summary The identity and spatial context of biomolecules (e.g., protein and RNA) in cancer cells are crucial components of their pathology. Therefore, a scalable and multiplexed imaging platform that can simultaneously map the protein and RNA landscapes tissue would be a vital tool towards deeply profiling and mapping cancer cell types in their spatial context. Extensive efforts have been made toward this end to reveal unprecedented details at both cellular level and molecular level. However, these methods generally lack high multiplexity or suffer low sensitivity as the target abundance decreases. In addition, highly multiplexed methods for co-imaging of protein and RNA at the whole tissue level still lag behind. We here aim to address these limitations by developing a versatile imaging platform for highly multiplexed, rapid, scalable proteomic and transcriptomic mapping of cell line and mammalian tissue samples with high-plex signal amplification. We propose to (Aim 1) develop a simple, highly controllable polymerase mediated iterative in situ DNA extension (ISE) and concatenation. We will demonstrate the application of ISE on the imaging of protein and RNA targets in both tissue and cell sample with high signal-to-noise and signal specificity. We will also (Aim 2) validate the scalability of ISE imaging in cell and tissue samples. We will optimize the technology to achieve spatial mapping of 50 to 100-plex protein and RNA targets in mammalian tissue samples. Finally, we will (Aim 3) validate ISE imaging in both FFPE and thick tissue, both normal and cancerous sample types. We will co-detect both RNA and protein tumor biomarkers in clinical FFPE samples and finally, we will integrate the ISE imaging methods with existing tissue clearing methods (iDISCO, CLARITY, etc.) to enable high-throughput and highly multiplexed tissue imaging from cellular level to molecular level for both normal and cancerous brain tissue. We will establish a platform for 50-plex imaging in hundreds micrometer to millimeter thick mammalian tissue specimens to unveil unprecedented detail in the tissue. The proposed work will deliver a comprehensive imaging toolset including a low-cost, simple design of orthogonal DNA probes for multiplexing imaging on protein and RNA molecules, and a scalable signal amplification method for multiplexed fluorescence imaging in different types of tissues. We envision that our technologies will be widely accessible and seamlessly incorporated into the pipelines, workflows, and coordinate frameworks of the mission for clinical researchers, pathologists, as well as the wider bio-imaging community to facilitate cancer research and clinical practice.
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)

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Peng Yin其他文献

Peng Yin的其他文献

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{{ truncateString('Peng Yin', 18)}}的其他基金

Light-Seq: Spatially targeted profiling of transcriptomic states in cells and tissue
Light-Seq:细胞和组织转录组状态的空间靶向分析
  • 批准号:
    10633918
  • 财政年份:
    2023
  • 资助金额:
    $ 42万
  • 项目类别:
Thermal-plex: fluidic-free, rapid sequential multiplexed imaging of RNA and protein in brain tissues
Thermal-plex:脑组织中 RNA 和蛋白质的无流体快速连续多重成像
  • 批准号:
    10640313
  • 财政年份:
    2023
  • 资助金额:
    $ 42万
  • 项目类别:
Decoding chromosome structure with multiplexed super-resolution microscopy
用多重超分辨率显微镜解码染色体结构
  • 批准号:
    10226100
  • 财政年份:
    2018
  • 资助金额:
    $ 42万
  • 项目类别:
Decoding chromosome structure with multiplexed super-resolution microscopy
用多重超分辨率显微镜解码染色体结构
  • 批准号:
    9762943
  • 财政年份:
    2018
  • 资助金额:
    $ 42万
  • 项目类别:
High-throughput single-molecule protein identification via super-resolution imaging
通过超分辨率成像进行高通量单分子蛋白质鉴定
  • 批准号:
    9980953
  • 财政年份:
    2018
  • 资助金额:
    $ 42万
  • 项目类别:
High-throughput single-molecule protein identification via super-resolution imaging
通过超分辨率成像进行高通量单分子蛋白质鉴定
  • 批准号:
    10242097
  • 财政年份:
    2018
  • 资助金额:
    $ 42万
  • 项目类别:
High-Throughput, Highly Multiplexed In Situ Proteomic Imaging of Human Tissues
人体组织的高通量、高度多重原位蛋白质组成像
  • 批准号:
    10215448
  • 财政年份:
    2018
  • 资助金额:
    $ 42万
  • 项目类别:
High-throughput single-molecule protein identification via super-resolution imaging
通过超分辨率成像进行高通量单分子蛋白质鉴定
  • 批准号:
    10478283
  • 财政年份:
    2018
  • 资助金额:
    $ 42万
  • 项目类别:
High-Throughput, Highly Multiplexed In Situ Proteomic Imaging of Human Tissues
人体组织的高通量、高度多重原位蛋白质组成像
  • 批准号:
    10026444
  • 财政年份:
    2018
  • 资助金额:
    $ 42万
  • 项目类别:
Super-resolution imaging via programmable autonomous blinking
通过可编程自主闪烁进行超分辨率成像
  • 批准号:
    9133898
  • 财政年份:
    2013
  • 资助金额:
    $ 42万
  • 项目类别:

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