Research Center for Spatiotemporal Lung Imaging and Omics

项目摘要 肺泡形成是正常人肺发育的后期阶段，是肺发育的最后一步。 成熟肺泡形成是一个动态的、协调的过程，需要准确的时空信息， 整合信号以发展复杂的肺泡结构。虽然取得了重要进展， 在我们对潜在的分子机制的理解方面， 肺泡形成为此，NHLBI建立了研究中心（RC），以创建一个分子图谱， 肺发育（LungMAP），关注从出生到儿童早期（约8岁）。第一阶段 LungMAP，我们的RC开发的资源，能够更详细地了解正常肺 发展到幼儿期。在LungMAP第2阶段，我们将应用我们成功的方法和我们的 将肺部发育分析扩展到成年早期以及人类疾病的最新技术; 关注支气管肺发育不良（BPD），这是早产儿最常见的发病率， 以延迟的或缺乏的肺成熟为特征。 在肺内，空间、解剖结构和功能之间的关系是基本的。所以我们的 方法包括新的无偏3D定量成像方法， 分辨率，以及细胞特异性组学：蛋白质组学（包括基于活性的蛋白质组学和 磷酸蛋白质组学）、脂质组学和代谢组学。整合这些互补的数据收集 方法有助于建立具有令人难以置信的分子宽度的细胞特异性空间图谱， 在正常和疾病状态下的发育中的肺的轮廓。 具体地说，我们将通过以下方法实现肺发育的综合分子图谱的目标： 以下目的：（1）正常和患病状态下人肺分子图谱的空间成像，（2） 正常和患病状态下人肺的分子图谱的细胞特异性组学，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可浏览定量三维“Google 蛋白质、脂质和代谢物在发育中的肺中的分布图，提供了许多新的见解 对了解正常人类肺部生物学和疾病发病机制的研究。 新的成像方法和一套综合的泛组学能力（即蛋白质组学， 磷酸化蛋白质组学、基于活性的蛋白质组学、脂质组学和代谢组学）， PNNL的单一实验室代表了研究中心的独特优势。

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.