Research Center for Spatiotemporal Lung Imaging and Omics

肺时空影像与组学研究中心

• 批准号: 10004709
• 负责人: Joshua N. Adkins
• 金额: $ 93.64万
• 依托单位: BATTELLE PACIFIC NORTHWEST LABORATORIES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10004709
• 关键词: 3-Dimensional; Alveolar; Alveolus; Anatomy; Atlases; Biology; Birth; Bronchopulmonary Dysplasia; Cells; Child; Childhood; Collaborations; Communities; Congenital diaphragmatic hernia; Cystic Fibrosis; Data; Data Analyses; Data Collection; Data Coordinating Center; Data Set; Development; Disease; Endothelial Cells; Epithelial Cells; Genes; Goals; Health; Human; Image; Immune; Interstitial Lung Diseases; Knowledge; Laboratories; Lipids; Lung; Lung diseases; Maps; Mass Spectrum Analysis; Methods; Molecular; Molecular Profiling; Morbidity - disease rate; Morphology; Mus; National Heart, Lung, and Blood Institute; Organ; Pathogenesis; Phase; Premature Infant; Process; Protein Deficiency; Proteins; Proteome; Proteomics; Protocols documentation; Publications; Pulmonary Hypertension; RNA; Research; Resolution; Resources; Role; Signal Transduction; Spatial Distribution; Structure; Structure of parenchyma of lung; Technology; Transcript; alveolar epithelium; base; cell type; data integration; data management; early childhood; emerging adult; high resolution imaging; human disease; human tissue; imaging approach; insight; lung development; lung imaging; lung maturation; metabolome; metabolomics; multiple omics; novel; phosphoproteomics; protein distribution; protein metabolite; quantitative imaging; spatiotemporal; stem cells; surfactant; web site

PROJECT ABSTRACT Alveologenesis characterizes the later stages of normal human lung development and is the final step of lung maturation. Alveologenesis is a dynamic, coordinated process that requires the accurate spatial and temporal integration of signals to develop the intricate alveolar structure. While important progress has been made, significant knowledge gaps remain in our understanding of the molecular mechanisms underlying alveologenesis. For this reason, NHLBI established Research Centers (RCs) to create a molecular atlas of the developing lung (LungMAP) focused from birth up to early childhood (~8 years). In the first phase of LungMAP, our RC developed resources that enabled a much more detailed understanding of normal lung development up to early childhood. In LungMAP Phase 2, we will apply our successful approaches and our newest technologies to extend analysis of lung development into early adulthood as well as human disease; focusing on bronchopulmonary dysplasia (BPD), the most common morbidity of preterm infants which is characterized by delayed or deficient lung maturation. Within the lung, the relationship between space, anatomy, and function is fundamental. Therefore, our approach includes new unbiased 3D quantitative imaging approaches implemented with high spatial resolution, as well as cell-specific omics: proteomics (including activity-based proteomics and phosphoproteomics), lipidomics, and metabolomics. The integration of these complementary data collection methods facilitates the establishment of a cell-specific spatial atlas with an incredible breadth of molecular profiles across the developing lung in normal and disease states. Specifically, we will accomplish our goal of an integrated molecular atlas of lung development through the following aims: (1) Spatial imaging for a molecular atlas of the human lung in normal and diseased states, (2) Cell-specific omics for a molecular atlas of the human lung in normal and diseased states, and (3) Managing data to facilitate collaboration and data integration. Overall, these aims will create unprecedented multi-scale browsable quantitative three-dimensional “Google Maps” of proteins, lipids, and metabolites across the developing lung, providing for many novel insights toward understanding both normal human lung biology and disease pathogenesis. The novel imaging approaches and the suite of integrated pan-omics capabilities (i.e. proteomics, phosphoproteomics, activity-based proteomics, lipidomics and metabolomics) developed and available in a single laboratory at PNNL represents a unique strength of the Research Center.

项目摘要 肺单齿表征了正常人肺发育的后期阶段，是肺的最后一步 成熟。肺单元是一个动态的，协调的过程，需要准确的空间和临时性 信号的整合以发展复杂的牙槽结构。尽管已经取得了重要进展，但 在我们对分子机制的理解中，重要的知识差距仍然存在 肺单术。因此，NHLBI建立了研究中心（RCS），以创建一个分子地图集 从出生到幼儿（约8年）开始发展肺（肺部）。在第一阶段 我们的RC开发了肺部 直到幼儿期的发展。在第2阶段，我们将采用我们的成功方法和我们的 将肺发育分析扩展到成年早期以及人类疾病的最新技术； 专注于支气管肺发育不良（BPD），早产儿最常见的发病率是 以延迟或不足的肺部成熟为特征。 在肺部，空间，解剖学和功能之间的关系是基本的。因此，我们的 方法包括使用高空间实施的新的无偏见的3D定量成像方法 分辨率以及细胞特异性的OMICS：蛋白质组学（包括基于活动的蛋白质组学和 磷酸蛋白质组学），脂肪组学和代谢组学。这些完整数据收集的集成 方法有助于建立具有令人难以置信的分子广度的细胞特异性空间地图集 正常和疾病状态下发育中的肺部的剖面。 具体而言，我们将通过 以下目的：（1）在正常和解散状态下人类肺的分子图谱的空间成像，（2） 在正常和解散状态下人类肺的分子图谱的细胞特异性元素，以及（3）管理 数据以促进协作和数据集成。 总体而言，这些目标将创建前所未有的多尺度浏览定量三维“ Google” 蛋白质，脂质和代谢产物的地图”遍布发育中的肺部，提供了许多新颖的见解 要了解正常的人肺生物学和疾病发病机理。 新颖的成像方法和综合泛组功能的套件（即蛋白质组学， 开发并提供 PNNL的单个实验室代表了研究中心的独特优势。