CAREER: LungEx for Probing Multiscale Mechanobiology of Pulmonary Respiration-Circulation Coupling in Real-Time
职业:LungEx 用于实时探索肺呼吸-循环耦合的多尺度力学生物学
基本信息
- 批准号:2239162
- 负责人:
- 金额:$ 56.65万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Standard Grant
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-15 至 2028-07-31
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
This Faculty Early Career Development (CAREER) grant will provide unprecedented insight into the real-time and multiscale lung mechanobiology that bridges single-air sac to whole-organ functions of the lung. This will be achieved by utilizing a novel transparent ribcage that provides transformative capabilities to probe lung mechanobiology at high spatial and temporal resolutions. The planned research will provide foundational understanding of lung function including respiration, circulation, and immunity, at the cellular level and in real-time. Understanding the lung function (and dysfunction) at an unprecedented spatiotemporal resolution will address key challenges in the emerging fields of lung mechanobiology and mechano-immunity. The focus on multidisciplinary and multiscale approaches, both experimental and mathematical, will also provide exciting opportunities for students on all levels to participate in the unexplored area of pulmonary biomechanics and mechanobiology. The central goal of this research and educational program is to inspire and train students from K-12 to graduate school to think conceptually about how quantitative and interdisciplinary approaches can help understand lung microphysiology. This work will utilize a novel platform, termed LungEx, that includes the ex vivo maintenance of the mouse lung in near in vivo physiological conditions. A key and novel element of LungEx is a transparent ribcage, termed “crystal” ribcage, with geometrical and physical properties of the intact native ribcage. Use of the crystal ribcage will allow, for the first time, visualization of the dynamics of lung microphysiology in real-time, at the cellular resolution, and over nearly the entire surface of the lung. Utilizing the transformative LungEx technology, the project goals will be achieved by 1) probing how alveolar distension is coupled to red blood cell trafficking and oxygen transport at the capillary level, 2) determining whether alveolar lymphatics serves as the main driver of flow in visceral lymphatics, and 3) probing the real-time dynamic mechanical interactions of immune cells with capillaries at the single cell level. By integrating this research with a carefully designed educational plan for students at all levels, we will train the next generation workforce in pulmonary biomechanics and mechanobiology to make discoveries in foundational pulmonary biology and physiology.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
这项教师早期职业发展(Career)资助将为实时和多尺度肺力学生物学提供前所未有的见解,将单个气囊连接到肺的整个器官功能。这将通过利用一种新型透明胸腔来实现,该胸腔提供了在高空间和时间分辨率下探测肺力学生物学的变革性能力。计划中的研究将在细胞水平上实时提供肺功能的基础知识,包括呼吸、循环和免疫。以前所未有的时空分辨率了解肺功能(和功能障碍)将解决肺力学生物学和力学免疫等新兴领域的关键挑战。对多学科和多尺度方法的关注,包括实验和数学,也将为各级学生提供令人兴奋的机会,参与肺生物力学和力学生物学的未开发领域。这项研究和教育计划的中心目标是激励和训练从K-12到研究生院的学生从概念上思考定量和跨学科方法如何帮助理解肺微生理学。这项工作将利用一种称为LungEx的新平台,包括在近体内生理条件下小鼠肺的离体维护。LungEx的一个关键和新颖元素是透明胸腔,称为“晶体”胸腔,具有完整天然胸腔的几何和物理特性。晶体胸腔的使用将首次实现肺微生理动态的实时可视化,在细胞分辨率下,几乎覆盖整个肺表面。利用革命性的LungEx技术,该项目的目标将通过以下方式实现:1)在毛细血管水平上探测肺泡扩张如何与红细胞运输和氧气运输耦合;2)确定肺泡淋巴是否作为内脏淋巴流动的主要驱动力;3)在单细胞水平上探测免疫细胞与毛细血管的实时动态力学相互作用。通过将这项研究与为各级学生精心设计的教育计划相结合,我们将培养下一代肺生物力学和力学生物学人才,以在基础肺生物学和生理学方面取得新发现。该奖项反映了美国国家科学基金会的法定使命,并通过使用基金会的知识价值和更广泛的影响审查标准进行评估,被认为值得支持。
项目成果
期刊论文数量(0)
专著数量(0)
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Hadi Tavakoli Nia其他文献
Hadi Tavakoli Nia的其他文献
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{{ truncateString('Hadi Tavakoli Nia', 18)}}的其他基金
Probing functioning lung at the cellular resolution in health and disease
以细胞分辨率探测健康和疾病中的肺功能
- 批准号:
10473112 - 财政年份:2022
- 资助金额:
$ 56.65万 - 项目类别:
Classifying malignant pulmonary nodules using biophysics-enhanced artificial intelligence
使用生物物理学增强人工智能对恶性肺结节进行分类
- 批准号:
10195872 - 财政年份:2021
- 资助金额:
$ 56.65万 - 项目类别:
Alleviating solid stress to overcome immunotherapy resistance in metastatic breast cancer
减轻实体应激以克服转移性乳腺癌的免疫治疗耐药性
- 批准号:
9328252 - 财政年份:2017
- 资助金额:
$ 56.65万 - 项目类别: