Pancreas Organ Specific Project

胰腺器官特定项目

• 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
• 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

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 组织内的分析需要协调许多分析技术的数据。我们将开发一个 直接从人类胰腺获取空间特定“组学”信息的多模式策略。这项工作将 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 教授是关键人员。建筑 根据之前开发人体肾脏组织图谱的工作，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 分子特异性。 MALDI timsTOF IMS 的高通量能力对于产生高通量至关重要 来自统计相关数量的正常胰腺样本的空间分辨率 3D 分子图像。马尔迪 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 用于分子鉴定的碎片实验。将使用空间特定的碎片来执行 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。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（例如自发荧光和染色显微镜）和胰腺特异性、高度多重 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 跨越多种人口统计数据的健康组织内的类型。目标 1：创建胰腺特异性 生物样本采集和管理计划。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。目标 3：开发 用于胰腺特异性 3D 分子成像的多模态表征流程。目标 4：扩大规模并 标准化胰腺特异性 3D 分子成像。为了实现这些目标，我们组建了一支高度 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。