Research Center for Spatiotemporal Lung Imaging and Omics

肺时空影像与组学研究中心

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要肺泡发生是正常人肺发育后期的特征，是肺发育的最后一步肺泡发生是一个动态的、协调的过程，需要精确的空间和时间。整合信号以形成复杂的肺泡结构虽然已经取得了重要进展，我们对潜在分子机制的理解仍然存在重大知识差距为此，NHLBI 建立了研究中心 (RC) 来创建肺泡发生的分子图谱。发育中的肺 (LungMAP) 重点关注从出生到幼儿期（~8 岁）的第一阶段。 LungMAP，我们的 RC 开发的资源，可以更详细地了解正常肺在 LungMAP 第二阶段，我们将应用我们的成功方法和我们的方法。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；重点关注支气管肺发育不良（BPD），这是早产儿最常见的疾病其特征是肺成熟延迟或不足。在肺内，空间、解剖结构和功能之间的关系至关重要。该方法包括利用高空间实现的新的无偏 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这些补充数据收集的整合。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图谱在正常和疾病状态下，肺部的轮廓变化。具体来说，我们将通过以下方式实现肺部发育综合分子图谱的目标以下目标：(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 发育中的肺部的蛋白质、脂质和代谢物的“地图”，提供了许多新的见解旨在了解正常人类肺部生物学和疾病发病机制。新颖的成像方法和一套集成的泛组学功能（即蛋白质组学、磷酸蛋白质组学、基于活性的蛋白质组学、脂质组学和代谢组学）在 PNNL 的单一实验室代表了该研究中心的独特优势。