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 细胞衰老是在正常组织中观察到的一种长期的、通常不可逆的生长停滞。 发展。虽然衰老对于组织重塑至关重要，对于防止受损细胞的恶变来说， 而在伤口愈合过程中，衰老细胞的异常堆积与多发性慢性 老年性疾病，如动脉粥样硬化、肺纤维化、神经退行性变等。衰老是 被认为是对各种应激因素的反应，包括端粒侵蚀、遗传毒性、营养缺乏、缺氧、 和线粒体功能障碍。生物分析核心将与Biosecimen核心合作， 通过集成和提供最先进的技术进行调查，是Sennet提案的关键资源 在分子、单细胞和整个组织水平上的衰老。核心由一支成就卓著的团队领导 成功利用这些特定平台并与以前和/或 目前的临床研究。与数据分析核心一起，生物分析核心将生成 描述单个细胞衰老细胞异质性和空间分布的多峰图谱 在包括肺、心脏、结肠、肌肉和皮肤在内的各种组织中的分辨率以及跨越不同阶段的 发育包括胎儿/婴儿、儿科(18岁)、青壮年(35岁)、中年人(55岁)和 老年人(&gt；55)。支持该联盟并提供所需的跨不同领域的衰老地图 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 经过验证的检测平台。最初的重点是肺组织，我们将系统地分析心脏、肌肉、皮肤 和结肠组织，提供上述所有年龄段的丰富衰老组织图。《生物》 分析核心有以下具体目标：1)提供最先进的高分辨率分子、细胞、 为了识别衰老的强大生物标记物，对生物标本进行组织水平的表征 和构建详细的组织图，2)收集和分析匹配的生物液，包括血液，脑脊液 体液、唾液和尿液，提供了更广泛的相互联系 组织和不同发育阶段，以及3)开发基于人类来源的微流控液滴 来自不同组织的有机化合物来模拟独特的系统，这些系统服从于测试新型药物有效性的扰动 用于干预衰老的药物。所有这些样本、衍生工具和数据都将提供给整个 组织地图中心联盟和我们的团队将致力于整合和优化数据的所有部分 生成管道，从组织收集和保存到数据生成、集成、分析和 释义。