Biological Analysis Core

生物分析核心

• 批准号: 10689785
• 负责人: ANDREW B. NIXON
• 金额: $ 74.67万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10689785
• 关键词: 18 year old; Adult; Aging; Atherosclerosis; Atlases; Biological; Biological Assay; Biological Markers; Blood; Bronchoalveolar Lavage; Cell Aging; Cell Nucleus; Cells; Cerebrospinal Fluid; Childhood; Chromatin; Chronic Disease; Clinical Research; Collaborations; Colon; Complex; Data; Data Analyses; Development; Dimensions; Elderly; Elements; Ensure; Environment; Enzyme-Linked Immunosorbent Assay; Epigenetic Process; Evaluation; Flow Cytometry; Foundations; Generations; Genus Mentha; Goals; Growth; Heart; Heterogeneity; Human; Hypoxia; Immune; In Vitro; Infant; Intervention; Lung; Malignant Neoplasms; Maps; Measurement; Measures; Methods; Microfluidics; Modeling; Molecular; Morphology; Muscle; Nerve Degeneration; Normal tissue morphology; Organ; Organoids; Phenotype; Prevention; Proteins; Pulmonary Fibrosis; Recording of previous events; Research; Research Personnel; Resolution; Resources; Saliva; Sampling; Science; Scientist; Skin; Spatial Distribution; Stains; Standardization; Structure of parenchyma of lung; System; TP53 gene; Technology; Tissue Banks; Tissue Preservation; Tissue atlas; Tissues; Transposase; Urine; Work; age group; beta-Galactosidase; biomarker identification; blood fractionation; cell injury; cell type; chromatin immunoprecipitation; efficacy testing; experience; fetal; functional genomics; genotoxicity; high dimensionality; histone modification; mitochondrial dysfunction; multimodality; multiple omics; novel; novel therapeutics; nutrient deprivation; response; senescence; stressor; telomere; tissue mapping; tool; transcriptome sequencing; transcriptomics; wound healing; young adult

ABSTRACT – Biological Analysis Core Cellular senescence is a prolonged and generally irreversible growth arrest observed in normal tissue development. While senescence is vital for tissue remodeling, for prevention of malignancy in damaged cells, and in wound healing, the aberrant accumulation of senescence cells is associated with multiple chronic diseases of aging such as atherosclerosis, pulmonary fibrosis, neurodegeneration and others. Senescence is seen as a response to various stressors including telomere erosion, genotoxicity, nutrient deprivation, hypoxia, and mitochondrial dysfunction. The Biological Analysis Core, in partnership with the Biospecimen Core, will be a critical resource for the SenNet proposal by integrating and delivering state-of-the-art technology to investigate senescence at the molecular, single-cell, and whole tissue level. The core is led by a team of highly accomplished research scientists who have successfully utilized these specific platforms in conjunction with previous and/or current clinical studies. Together with the Data Analysis Core, the Biological Analysis Core will generate multimodal atlases that characterize the heterogeneity and spatial distribution of senescent cells at single cell resolution in various tissues including lung, heart, colon, muscle, and skin and across different stages of development consisting of fetal/infant, pediatric (<18 years old), young adults (<35), middle adults (<55), and older adults (>55). To support the consortium and provide the requisite set of senescence maps across different tissues, Biological Analysis Core will utilize a comprehensive repertoire of highly standardized and/or formally validated assay platforms. With the initial focus on lung tissue, we will systematically profile heart, muscle, skin and colon tissues to provide rich tissue maps of senescence across all above-defined age groups. The Biological Analysis Core has the following Specific Aims: 1) to provide high resolution state-of-the-art molecular, cellular, and tissue-level characterization of biospecimens for the purpose of identifying robust biomarkers of senescence and constructing detailed tissue maps, 2) to collect and analyze matching biofluids including blood, cerebrospinal fluid, saliva, and urine, providing a broader interconnection between the senescence maps across multiple tissues and at varying developmental stages, and 3) to develop human-derived microfluidic-based droplet organoids from various tissues to model unique systems amenable to perturbations that test the efficacy of novel drugs for senescence intervention. All of these samples, derivatives, and data will be available to the entire Tissue Mapping Center consortium and our team will work to integrate and optimize all parts of the data generation pipeline, from tissue collection and preservation to data generation, integration, analysis, and interpretation.

摘要 - 生物分析核心 细胞感应是在正常组织中观察到的延长且通常不可逆的生长停滞 发展。虽然感应对于组织重塑至关重要，但对于预防损伤细胞中的恶性肿瘤至关重要，但 在伤口愈合中，感应细胞的异常积累与多个慢性有关 衰老的疾病，例如动脉粥样硬化，肺纤维化，神经退行性变化等。衰老是 将其视为对各种压力源的反应，包括端粒侵蚀，遗传毒性，养分剥夺，缺氧， 和线粒体功能障碍。生物分析核心与生物循环核心合作将是 通过整合和交付最先进的技术来调查Sennet提案的关键资源 在分子，单细胞和整个组织水平上的感应。核心由一支高度成就的团队领导 成功利用这些特定平台以及以前和/或的研究科学家 当前的临床研究。与数据分析核心一起，生物分析核心将产生 多模式图谱，表征了单细胞在Senscent细胞的异质性和空间分布 各种组织的分辨率，包括肺，心脏，结肠，肌肉和皮肤以及不同阶段 由胎儿/婴儿，小儿（<18岁），年轻人（<35），中年成年人（<55）和 老年人（> 55）。支持财团，并提供不同的衰老图。 组织，生物分析核心将利用高度标准化和/或正式的全面曲目 经过验证的测定平台。最初关注肺组织，我们将系统地介绍心脏，肌肉，皮肤 和结肠组织可在所有上述年龄段中提供丰富的感应组织图。生物学 分析核心具有以下特定目的：1）提供高分辨率的最先进的分子，细胞， 生物测量的组织级表征是为了鉴定衰老的稳健生物标志物 并构建详细的组织图，2）收集和分析匹配的生物流体，包括血液，脑脊 流体，唾液和尿液，在多个跨多个的感应图之间提供更广泛的互连 组织和不同的发育阶段，以及3）发展基于人体微流体的液滴 从各种组织到模拟独特系统的类器官，可与扰动一起测试新颖的效率 用于感应干预的药物。所有这些样本，衍生词和数据都将用于整个 组织映射中心财团和我们的团队将努力整合和优化数据的所有部分 从组织收集和制备到数据生成，集成，分析和 解释。