Investigation of Immune Cell Trafficking in Complex Cellular Environment

复杂细胞环境中免疫细胞贩运的研究

基本信息

  • 批准号:
    RGPIN-2021-03346
  • 负责人:
  • 金额:
    $ 4.23万
  • 依托单位:
  • 依托单位国家:
    加拿大
  • 项目类别:
    Discovery Grants Program - Individual
  • 财政年份:
    2021
  • 资助国家:
    加拿大
  • 起止时间:
    2021-01-01 至 2022-12-31
  • 项目状态:
    已结题

项目摘要

BACKGROUND: Immune cell trafficking is fundamentally important for the biology of immune cells with direct relevance to physiological processes. The trafficking of immune cells is orchestrated by various microenvironmental factors such as chemical concentration gradients and electric fields (EF). Cell migration directed by electrochemical fields have been well demonstrated in vitro and in vivo. However, the underlying mechanisms are far from being well understood. Particularly, there is a lack of knowledge about how immune cells migrate in response to complex environmental guiding signals that are inter-coupled and dynamically vary in space and time. My previous studies through the Discovery grant identified the interesting CCR7-mediated combinatorial guiding mechanism for T cell migration, the migratory memory effect of immune cells in chemical fields and EF, and migratory interactions between different cell types in complex guiding microenvironment, which motivated further explorations. LONG-TERM GOAL: My Discovery research program aims at integrating cell biology and immunology research approaches, biophysical analysis and novel microfluidic tools to achieve a better understanding of immune cell trafficking in complex cellular environments. NEXT FIVE-YEAR RESEARCH PLANS: My Discovery research program in the next 5 year will critically investigate the fundamental mechanisms for immune cell migration and cell-cell interactions in complex electrochemical guiding environments through the following objectives: Objective I: Investigate CCR7-mediated guiding mechanism for T cell migration in complex chemoattractant fields. The focus is to better understand how T cell migration is mediated by 1) co-existing fields of CCR7 ligands and Sphingosine-1-phosphate; 2) co-existing fields of CCR7 ligands and CXCL13. Objective II: Examine the memory effect of immune cell migration in electrochemical fields. In this direction, I will research 1) the impact of spatiotemporally varying chemical fields on immune cell migration; 2) immune cell migratory behavious in response to dynamically changing EF. Objective III: Explore cell-cell migratory interactions in electrochemical fields. I will direct this part of my research program to explore how cell-cell migratory interactions are mediated 1) by EF alone; and furthermore 2) by co-existing chemical fields and EF. SIGNIFICANCE: This work will contribute significantly to the understanding of the complex process of immune cell migration and trafficking. Importantly, the interdisciplinary training through my Discovery program will develop young scientists able to conduct research at the interfaces of physical sciences, engineering and life sciences. In addition to acquiring a solid scientific backgrounds in cell migration, the students will be trained for hands-on research skills and develop strong scientific communication ability thereby preparing them for careers in both academic and industrial sectors.
背景:免疫细胞运输对于与生理过程直接相关的免疫细胞生物学具有根本重要性。免疫细胞的运输由各种微环境因素如化学浓度梯度和电场(EF)协调。电化学场引导的细胞迁移已经在体外和体内得到了很好的证明。然而,根本的机制还远未得到很好的理解。特别地,缺乏关于免疫细胞如何响应于相互耦合并且在空间和时间上动态变化的复杂环境引导信号而迁移的知识。我之前通过Discovery资助的研究发现了有趣的CCR 7介导的T细胞迁移的组合引导机制,免疫细胞在化学场和EF中的迁移记忆效应,以及不同细胞类型在复杂引导微环境中的迁移相互作用,这激发了进一步的探索。长期目标:我的发现研究计划旨在整合细胞生物学和免疫学研究方法,生物物理分析和新型微流体工具,以更好地了解复杂细胞环境中的免疫细胞贩运。 未来五年研究计划:我的发现研究计划在未来5年将严格调查免疫细胞迁移和细胞间相互作用在复杂的电化学引导环境中的基本机制,通过以下目标:目的一:调查CCR 7介导的T细胞迁移在复杂的化学引诱物领域的指导机制。重点是更好地理解T细胞迁移如何通过1)CCR 7配体和鞘氨醇-1-磷酸的共存区域; 2)CCR 7配体和CXCL 13的共存区域介导。目的二:研究电化学场中免疫细胞迁移的记忆效应。在这个方向上,我将研究1)时空变化的化学场对免疫细胞迁移的影响; 2)免疫细胞迁移行为对动态变化的EF的反应。目的三:探讨电化学场中细胞间迁移的相互作用。我将指导我的研究计划的这一部分,以探索细胞迁移相互作用是如何介导的1)EF单独;此外2)通过共存的化学领域和EF。意义:这项工作将大大有助于理解免疫细胞迁移和贩运的复杂过程。重要的是,通过我的发现计划的跨学科培训将培养年轻科学家能够在物理科学,工程和生命科学的接口进行研究。除了在细胞迁移方面获得坚实的科学背景外,学生还将接受实践研究技能的培训,并培养强大的科学沟通能力,从而为学术和工业部门的职业生涯做好准备。

项目成果

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Lin, Francis其他文献

E-cadherin plays an essential role in collective directional migration of large epithelial sheets.
  • DOI:
    10.1007/s00018-012-0951-3
  • 发表时间:
    2012-08
  • 期刊:
  • 影响因子:
    8
  • 作者:
    Li, Li;Hartley, Robert;Reiss, Bjoern;Sun, Yaohui;Pu, Jin;Wu, Dan;Lin, Francis;Hoang, Trung;Yamada, Soichiro;Jiang, Jianxin;Zhao, Min
  • 通讯作者:
    Zhao, Min
Regio-Specific Selenium Substitution in Non-Fullerene Acceptors for Efficient Organic Solar Cells
  • DOI:
    10.1021/acs.chemmater.9b01242
  • 发表时间:
    2019-09-10
  • 期刊:
  • 影响因子:
    8.6
  • 作者:
    Lin, Francis;Zuo, Lijian;Jee, Alex K-Y
  • 通讯作者:
    Jee, Alex K-Y
Activated T lymphocytes migrate toward the cathode of DC electric fields in microfluidic devices
  • DOI:
    10.1039/c0lc00371a
  • 发表时间:
    2011-01-01
  • 期刊:
  • 影响因子:
    6.1
  • 作者:
    Li, Jing;Nandagopal, Saravanan;Lin, Francis
  • 通讯作者:
    Lin, Francis
Microfluidic device for studying cell migration in single or co-existing chemical gradients and electric fields
  • DOI:
    10.1063/1.4718721
  • 发表时间:
    2012-06-01
  • 期刊:
  • 影响因子:
    3.2
  • 作者:
    Li, Jing;Zhu, Ling;Lin, Francis
  • 通讯作者:
    Lin, Francis
An all-on-chip method for testing neutrophil chemotaxis induced by fMLP and COPD patient's sputum
  • DOI:
    10.1142/s2339547816500035
  • 发表时间:
    2016-06-01
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Wu, Jiandong;Hillier, Craig;Lin, Francis
  • 通讯作者:
    Lin, Francis

Lin, Francis的其他文献

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{{ truncateString('Lin, Francis', 18)}}的其他基金

Investigation of Immune Cell Trafficking in Complex Cellular Environment
复杂细胞环境中免疫细胞贩运的研究
  • 批准号:
    RGPIN-2021-03346
  • 财政年份:
    2022
  • 资助金额:
    $ 4.23万
  • 项目类别:
    Discovery Grants Program - Individual
Investigation of Immune Cell Trafficking in Complex Cellular Environment
复杂细胞环境中免疫细胞贩运的研究
  • 批准号:
    RGPIN-2014-04789
  • 财政年份:
    2019
  • 资助金额:
    $ 4.23万
  • 项目类别:
    Discovery Grants Program - Individual
Investigation of Immune Cell Trafficking in Complex Cellular Environment
复杂细胞环境中免疫细胞贩运的研究
  • 批准号:
    RGPIN-2014-04789
  • 财政年份:
    2017
  • 资助金额:
    $ 4.23万
  • 项目类别:
    Discovery Grants Program - Individual
The dufflebag project: development of a microfluidic point-of-care system for infectious disease diagnosis
行李袋项目:开发用于传染病诊断的微流体护理点系统
  • 批准号:
    499151-2016
  • 财政年份:
    2016
  • 资助金额:
    $ 4.23万
  • 项目类别:
    Collaborative Research and Development Grants
Developing Novel Integrated Point-of-Care Systems for Chronic Kidney Disease Biomarkers Measurements
开发用于慢性肾脏病生物标志物测量的新型集成护理点系统
  • 批准号:
    462376-2014
  • 财政年份:
    2016
  • 资助金额:
    $ 4.23万
  • 项目类别:
    Collaborative Health Research Projects
Investigation of Immune Cell Trafficking in Complex Cellular Environment
复杂细胞环境中免疫细胞贩运的研究
  • 批准号:
    RGPIN-2014-04789
  • 财政年份:
    2016
  • 资助金额:
    $ 4.23万
  • 项目类别:
    Discovery Grants Program - Individual
Developing Novel Integrated Point-of-Care Systems for Chronic Kidney Disease Biomarkers Measurements
开发用于慢性肾脏病生物标志物测量的新型集成护理点系统
  • 批准号:
    462376-2014
  • 财政年份:
    2015
  • 资助金额:
    $ 4.23万
  • 项目类别:
    Collaborative Health Research Projects
Investigation of Immune Cell Trafficking in Complex Cellular Environment
复杂细胞环境中免疫细胞贩运的研究
  • 批准号:
    RGPIN-2014-04789
  • 财政年份:
    2015
  • 资助金额:
    $ 4.23万
  • 项目类别:
    Discovery Grants Program - Individual
Developing Novel Integrated Point-of-Care Systems for Chronic Kidney Disease Biomarkers Measurements
开发用于慢性肾脏病生物标志物测量的新型集成护理点系统
  • 批准号:
    462376-2014
  • 财政年份:
    2014
  • 资助金额:
    $ 4.23万
  • 项目类别:
    Collaborative Health Research Projects
Investigation of Immune Cell Trafficking in Complex Cellular Environment
复杂细胞环境中免疫细胞贩运的研究
  • 批准号:
    RGPIN-2014-04789
  • 财政年份:
    2014
  • 资助金额:
    $ 4.23万
  • 项目类别:
    Discovery Grants Program - Individual

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Investigation of Immune Cell Trafficking in Complex Cellular Environment
复杂细胞环境中免疫细胞贩运的研究
  • 批准号:
    RGPIN-2021-03346
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    2022
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