Nanodelivery of functional proteins to phagosomal membranes

将功能蛋白纳米递送至吞噬体膜

基本信息

  • 批准号:
    10365947
  • 负责人:
  • 金额:
    $ 70.4万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-03-09 至 2025-02-28
  • 项目状态:
    未结题

项目摘要

Project Summary Extracellular vesicles (EVs) are cell-derived membranous structures carrying transmembrane proteins and luminal cargo including soluble cytoplasmic proteins and nucleic acids. They are a heterogeneous group of particles generally classified according to subcellular origin, dimension, and tetraspanin surface expression. Circulating EVs may act as nanocontainers capable of recognizing target cells through membrane receptors and communicating cargo through membrane fusion, a notoriously low probability process. Interaction with recipient cells can lead to their acquisition of EV surface proteins and luminal contents although the mechanisms controlling this exchange remain unclear. Their complex cargo and well as surface markers are highly variable with respect to functional impact and dependent upon the tissue context from which they are released. A central focus of the proposed work is the isolation and identification of functionally competent small EVs (30-150 nm) carrying an ion channel of interest which can then be transferred to a naïve, non-expressing cell. Functionally significant EV-mediated channel translocation from one cell to another would require a high density of channel expression per vesicle during EV biosynthesis in the donor cell and reliable fusion with the plasma membrane and endocytic/phagocytic compartments of recipient cells. In order to facilitate EV membrane fusion we will co-express the viral protein fusogen hemagglutinin subtype 7 (HA). Expression of a genetically engineered blue light-activated Ca2+ channel switch (BACCS) which opens the Ca2+ selective ORAI ion channel in response to light will be used in the design of screening strategies exploring vesicle fusion and channel transfer. The light- sensitive probe will be used as screening tool for functional Ca2+ channel transfer in non-responsive recipient cells via isolated EVs derived from BACCS-ORAI expressing cells. Once we have established optimal conditions for EV-mediated channel transfer, we will leverage our experience in the study of the anion channel Cystic Fibrosis Transmembrane conductance Regulator (CFTR) in murine alveolar macrophages (AMs) and epithelial cells and study the EV-mediated transfer of CFTR to cftr-/- cells in the context of the disease of cystic fibrosis (CF) using adoptive transfer techniques.
项目总结

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Chloride-hydrogen antiporters ClC-3 and ClC-5 drive osteoblast mineralization and regulate fine-structure bone patterning in vitro.
氯化物 - 氢抗抗植物CLC-3和CLC-5驱动成骨细胞矿化,并在体外调节精细结构骨图案。
  • DOI:
    10.14814/phy2.12607
  • 发表时间:
    2015-11
  • 期刊:
  • 影响因子:
    2.5
  • 作者:
    Larrouture QC;Nelson DJ;Robinson LJ;Liu L;Tourkova I;Schlesinger PH;Blair HC
  • 通讯作者:
    Blair HC
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DEBORAH J. NELSON其他文献

DEBORAH J. NELSON的其他文献

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{{ truncateString('DEBORAH J. NELSON', 18)}}的其他基金

Nanodelivery of functional proteins to phagosomal membranes
将功能蛋白纳米递送至吞噬体膜
  • 批准号:
    9901551
  • 财政年份:
    2015
  • 资助金额:
    $ 70.4万
  • 项目类别:
Nanodelivery of functional proteins to phagosomal membranes
将功能蛋白纳米递送至吞噬体膜
  • 批准号:
    10115786
  • 财政年份:
    2015
  • 资助金额:
    $ 70.4万
  • 项目类别:
Phagosomal Ion Channels as Therapeutic Targets
吞噬体离子通道作为治疗靶点
  • 批准号:
    9213389
  • 财政年份:
    2015
  • 资助金额:
    $ 70.4万
  • 项目类别:
Chloride Channel Involvement in Diabetes
氯离子通道参与糖尿病
  • 批准号:
    8293392
  • 财政年份:
    2009
  • 资助金额:
    $ 70.4万
  • 项目类别:
Chloride Channel Involvement in Diabetes
氯离子通道参与糖尿病
  • 批准号:
    8098817
  • 财政年份:
    2009
  • 资助金额:
    $ 70.4万
  • 项目类别:
Chloride Channel Involvement in Diabetes
氯离子通道参与糖尿病
  • 批准号:
    7923878
  • 财政年份:
    2009
  • 资助金额:
    $ 70.4万
  • 项目类别:
Chloride Channel Involvement in Diabetes
氯离子通道参与糖尿病
  • 批准号:
    7736410
  • 财政年份:
    2009
  • 资助金额:
    $ 70.4万
  • 项目类别:
Role of Ion Channel in Mononuclear Phagocyte Activation
离子通道在单核吞噬细胞激活中的作用
  • 批准号:
    7912041
  • 财政年份:
    2009
  • 资助金额:
    $ 70.4万
  • 项目类别:
Chloride Channel Involvement in Diabetes
氯离子通道参与糖尿病
  • 批准号:
    7500433
  • 财政年份:
    2007
  • 资助金额:
    $ 70.4万
  • 项目类别:
Alternate CI-secretory pathways in cystic fibrosis
囊性纤维化中的替代 CI 分泌途径
  • 批准号:
    6517779
  • 财政年份:
    2001
  • 资助金额:
    $ 70.4万
  • 项目类别:

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ATTAC 时间:针对 gp100 细胞的 T 细胞过继转移来治疗 LAM
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