Elucidating spatial and temporal dynamics of macrophage polarization using bioluminescence microscopy

使用生物发光显微镜阐明巨噬细胞极化的空间和时间动态

• 批准号: 10276291
• 负责人: Elizabeth C Wayne
• 金额: $ 34.34万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10276291
• 关键词: Address; Biocompatible Materials; Bioluminescence; Biosensor; Cells; Cellular Metabolic Process; Data; Development; Diagnostic tests; Disease; Drug Delivery Systems; Environment; Genomics; Goals; Implant; Knowledge; Lead; Measures; Metals; Microscopy; Monitor; Pathologic Processes; Patient-Focused Outcomes; Patients; Physiological Processes; Proteomics; Research; Solid Neoplasm; Stimulus; System; Technology; Time; Work; base; bioluminescence imaging; extracellular; imaging system; implementation barriers; improved; macrophage; nanoparticle; nanoparticle drug; new therapeutic target; novel strategies; personalized medicine; polarized cell; programs; protein expression; stem cell differentiation; success; synthetic biology; therapy development; tool

Project Summary/Abstract: Macrophage polarization is involved in the progression of normal physiological and pathological processes. The near universal importance of macrophage has led to widescale assessment of the genomic and proteomic to classify their function. However, it is still a challenge to measure macrophage polarization in real time such as in the context of assessing the status of a biomaterial implant or the efficacy of a nanoparticle drug delivery system in a solid tumor. Our preliminary data show that bioluminescence microscopy is able to deliver the protein expression data valuable for macrophage polarization combined the cell tracking capability of traditional imaging system. This research program will address the current gap in real-time assessment of macrophage polarization by 1) further developing the technology to measure macrophage polarization dynamics using bioluminescence microscopy and 2) assessing the intrinsic and extracellular environmental stimuli that are most important for sensing macrophage polarization in a diseased environment context. To accomplish these goals, we will employ ex-vivo culture systems and live bioluminescence imaging. This work will identify novel strategies for measuring macrophage polarization and validate the importance of analyzing polarization in a disease context. Ultimately, this research will lead to new strategies for synthetic biology development, enhancement of diagnostic testing and development of new therapeutic targets. In addition, the knowledge and tools developed can be applied to other cells where polarization is paramount such as stem cell differentiation, chemoattraction, and cell metabolism.

项目概要/摘要： 巨噬细胞极化参与正常生理和病理过程 流程.巨噬细胞几乎普遍的重要性导致了对 从基因组学和蛋白质组学的角度对它们的功能进行分类。然而，衡量起来仍然是一个挑战 例如在评估生物材料状态的情况下 纳米颗粒药物递送系统在实体瘤中的植入或功效。我们的初步 数据显示，生物发光显微镜能够提供有价值的蛋白质表达数据， 对于巨噬细胞极化，结合了传统成像系统的细胞跟踪能力。 这项研究计划将解决目前的差距，实时评估巨噬细胞 通过1）进一步开发测量巨噬细胞极化的技术 使用生物发光显微镜的动力学和2）评估内源性和细胞外 环境刺激是最重要的感知巨噬细胞极化在患病 环境背景。为了实现这些目标，我们将采用离体培养系统， 生物发光成像这项工作将确定测量巨噬细胞的新策略 极化，并验证在疾病背景下分析极化的重要性。最后， 这项研究将为合成生物学的发展、增强 诊断测试和开发新的治疗靶点。此外，知识和 开发的工具可应用于极化至关重要的其他细胞，例如干细胞 分化、化学吸引和细胞代谢。