Pancreas Organ Specific Project

胰腺器官特定项目

基本信息

批准号：
10480802
负责人：
ALVIN C POWERS
金额：
$ 28.16万
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/10480802
关键词：
3-Dimensional Academic Medical Centers Acinar Cell Address Analytical Chemistry Atlases Biological Assay Blood Vessels Cell physiology Cells 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 atlas 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 facilities imaging modality improved indexing insight instrumentation islet mass spectrometric imaging molecular imaging multimodality nutrient absorption pancreas imaging professor reconstruction single cell analysis single cell technology single-cell RNA sequencing spatial relationship three dimensional structure tissue mapping

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。组织内的分析需要协调许多分析技术的数据。这项工作将采用多模式策略直接从人类胰腺获取空间特定的“组学”信息。利用质谱研究中心独特的仪器能力和专业知识 (MSRC)，其中 Spraggins、Caprioli、Schey、Gutierrez 和 Van de Plas 教授是大楼的关键人员。根据之前开发的人体肾脏组织工作图谱，我们将整合超高速、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，具有前所未有的空间保真度和 MALDI timsTOF IMS 的高通量能力对于产生高通量至关重要。来自技术相关数量的正常胰腺样本的空间分辨率 3D 分子图像。 IMS 将提供将离子图像链接到基于正交 LC 所需的特异性和质量准确度将使用空间特异性进行碎片化实验。表面采样方法，以与 IMS 兼容的方式从组织中生成 LC-MS/MS 数据并能够集成到 HuBMAP 组织图谱中，以最大化从成像中收集的信息。实验并为数据驱动的图像融合和 3D 重建奠定基础分析核心研究策略，我们还将开发收集各种基于显微镜的图像的方法模式（例如高度自发荧光和染色显微镜）和胰腺特异性、多重检测使用 CODEX 进行免疫荧光。通过使用我们的多模式管道，我们建议绘制胰腺细胞的空间关系目标 1：创建胰腺特异性的类型。目标 2：建立标准化的预分析流程。样品制备、确定组织正常情况并提供质量控制指标。用于胰腺特异性 3D 分子成像的多模态表征流程目标 4：规模化和规模化。为了实现这些目标，我们组装了一个高度标准化的胰腺特异性 3D 分子成像。互动且已建立的研究团队由内分泌学领域的互补专业知识组成，分析化学和数据科学。