Pancreas Organ Specific Project

胰腺器官特定项目

基本信息

批准号：
10117952
负责人：
ALVIN C POWERS
金额：
$ 16.74万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-30 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10117952
关键词：
3-Dimensional Academic Medical Centers Acinar Cell Address Analytical Chemistry Atlases Biological Assay Blood Vessels Cell physiology Cells Cellular Structures Clinical Collection Complement Complex Cooperative Human Tissue Network D Cells Data Data Analyses Data Science Digestion Disease Duct (organ) structure Duodenum Emerging Technologies Endocrine Endocrinology Ensure Environment Enzymes Excision Exocrine pancreas Extracellular Matrix Eye Food Funding G Cells Gene Expression Genetic Transcription Glean Glucagon Goals Health Heterogeneity Histologic Human Human BioMolecular Atlas Program Human Characteristics Human Resources Image Imaging Techniques Immunofluorescence Immunologic Individual Insulin Ions Islets of Langerhans Kidney Knowledge Link Lipids Maps Mass Spectrum Analysis Metabolic Methods Microscopy Modality Molecular Molecular Profiling Morphology Multimodal Imaging Multiomic Data Normalcy Operative Surgical Procedures Organ Output Pancreas Pancreatic Polypeptide Preparation Proteins Quality Control Research Research Personnel Resolution Rodent Sampling Somatostatin Source Spatial Distribution Specificity Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Speed Stains Standardization Surface Technology Tissue Banks Tissue imaging Tissues Transcript United States National Institutes of Health Work base blood glucose regulation cell type data quality demographics experimental study extracellular ghrelin human imaging imaging modality improved indexing insight instrumentation islet molecular imaging multimodality nutrient absorption pancreas imaging professor reconstruction single cell analysis single cell technology single-cell RNA sequencing spatial relationship three dimensional structure

项目摘要

PROJECT SUMMARY – Pancreas Organ Specific Project. Comprehensive 3-dimensional biomolecular analysis within tissues requires the coordination of data from many analytical technologies. We will develop a multimodal strategy to obtain spatially specific ‘omics’ information directly from human pancreas. This work will leverage the unique instrumentation capabilities and expertise of the Mass Spectrometry Research Center (MSRC) in which Professors Spraggins, Caprioli, Schey, Gutierrez and Van de Plas are key personnel. Building from previous work developing atlases of human kidney tissue, we will integrate ultra-high speed, high spatial resolution (<10μm) MALDI timsTOF IMS with high mass resolution (>40,000 Resolving Power, <2 ppm mass accuracy) for molecular imaging of human pancreata with an unprecedented combination of spatial fidelity and molecular specificity. The high-throughput capabilities of MALDI timsTOF IMS will be critical for generating high- spatial resolution 3-D molecular images from statistically relevant numbers of normal pancreas samples. MALDI IMS will provide the specificity and mass accuracy necessary to link ion images to orthogonal LC-based fragmentation experiments for molecular identification. Fragmentation will be performed using spatially specific surface sampling approaches to produce LC-MS/MS data from tissues in a manner that is compatible with IMS and capable of being integrated into HuBMAP tissue atlases. To maximize information gleaned from imaging experiments and lay the groundwork for data-driven image fusion and 3-D reconstruction outlined in the Data Analysis Core Research Strategy, we will also develop methods for collecting various microscopy-based image modalities (e.g. autofluorescence and stained microscopy) and pancreas specific, highly multiplexed immunofluorescence using CODEX. Through the use of our multimodal pipeline, we propose to map spatial relationships of pancreas cell types within healthy tissue across a multitude of demographics. Aim 1: To create a pancreas-specific biospecimen collection and management plan. Aim 2: To establish a pre-analytical pipeline for standardizing sample preparation, determining tissue normalcy, and providing quality control metrics. Aim 3: To develop a multimodal characterization pipeline for pancreas-specific 3-D molecular imaging. Aim 4: To scale and standardize pancreas-specific 3-D molecular imaging. To accomplish these aims, we have assembled a highly interactive and established team of investigators consisting of complementary expertise in endocrinology, analytical chemistry, and data science.

项目摘要 - 胰腺器官特定项目。综合3维生物分子组织内的分析需要许多分析技术的数据协调。我们将发展一个直接从人类胰腺获得经常获得特定特定“ OMIC”信息的多模式策略。这项工作将利用质谱研究中心的独特仪器功能和专业知识（MSRC）其中Spraggins，Caprioli，Schey，Gutierrez和Van de Plas教授是关键人员。建筑从以前开发人类肾脏组织的地图的工作中，我们将整合超高速度，高空间分辨率（<10μm）MALDI TIMSTOF IMS具有高质量分辨率（> 40,000分辨率，<2 ppm质量精度），用于人类胰腺的分子成像，并具有空间保真度和分子特异性。 MALDI TIMSTOF IMS的高通量功能对于产生高来自统计相关数量的正常胰腺样品的空间分辨率3-D分子图像。马尔迪 IMS将提供将离子图像与基于正交LC连接的特异性和质量精度分子鉴定的碎片实验。碎片将使用空间特定的表面采样方法以与IMS兼容的方式从TIMS产生LC-MS/MS数据并能够被整合到Hubmap组织地图集中。从成像中最大化信息实验并为数据驱动的图像融合和数据中概述的3-D重建奠定了基础分析核心研究策略，我们还将开发用于收集各种基于显微镜图像的方法模态（例如自动荧光和染色显微镜）和胰腺特异性，高度多路复用使用法典免疫荧光。通过使用多模式管道，我们建议映射胰腺细胞的空间关系在许多人口统计学中，健康组织中的类型。目标1：创建一个特定胰腺的生物测量收集和管理计划。目标2：建立标准化的分析前管道目标3：开发样品制备，确定组织正常水平并提供质量控制指标。胰腺特异性3-D分子成像的多模式表征管道。目标4：扩展和标准化胰腺特异性3-D分子成像。为了实现这些目标，我们组装了一个高度的互动和成熟的调查人员团队，包括内分泌专业知识，分析化学和数据科学。