Human Tissue and Genomics Core

人体组织和基因组学核心

• 批准号: 9091533
• 负责人: Hans H. Herfarth
• 金额: $ 29.04万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9091533
• 关键词: Address; Animal Experimentation; Animal Model; Automobile Driving; Bioinformatics; Biological; Biological Assay; Biopsy; Cells; Chromatin; Clinical; DNA; Data; Data Analyses; Databases; Development; Diagnostic; Disease; Enteral; Excision; Experimental Models; Family member; Formaldehyde; Freezing; Gene Expression; Gene Expression Regulation; Gene Targeting; Genes; Genetic; Genome; Genomics; Goals; High-Throughput Nucleotide Sequencing; Human; Immune; Immunophenotyping; Individual; Inflammatory Bowel Diseases; Inflammatory Response; Inflammatory disease of the intestine; Interleukin-10; Interleukin-12; Intestines; Link; Mediating; Microbe; Modeling; Molecular; Mus; Operative Surgical Procedures; Pathogenesis; Patients; Pattern; Peripheral Blood Mononuclear Cell; Phenotype; Play; Population; Process; Proteins; RNA; Regulator Genes; Regulatory Element; Research Infrastructure; Research Personnel; Resources; Role; Sampling; Science; Serum; Single Nucleotide Polymorphism; Technical Expertise; Testing; Therapeutic; Tissue Banking; Tissue Banks; Tissues; United States National Institutes of Health; Variant; base; chromatin immunoprecipitation; clinical phenotype; computerized data processing; cost; deep sequencing; disease phenotype; disorder control; functional genomics; genome wide association study; high throughput screening; human disease; human tissue; innovation; interest; meetings; microbiota; microorganism interaction; new technology; programs; tool; transcription factor

The primary goal of Core B is to provide individual projects with intestinal tissue, isolated cell populations, and functional genomic information from clinically characterized IBD patients and healthy controls. This core will overcome a widely acknowledged roadblock in the use of animal models - direcfing animal research to address questions that will be directly translatable to human IBD. The data and tissue banks and novel technologies developed through this core will allow investigators the opportunity to correlate molecular findings across model species to human diseases. Core B will leverage substanfial existing resources and expertise at UNC. There is an established infrastructure for obtaining and processing surgical resecfions and intestinal biopsies. The "Tissue" component of Core B will process and provide frozen intestinal tissue; RNA and protein extracts from intestinal tissue, deidentified clinical information on disease phenotype, and at the request of invesfigators, isolated intestinal cell populations. Where required, the core will be able to provide matched serum in peripheral blood mononuclear cell populafions as well as DNA to correlate immunophenotype, clinical phenotype with genetic background. Understanding the molecular basis of human IBD is far from being achieved. High throughput assays that permit the identification of gene regulatory networks in a heterogeneous disease like IBD is of paramount importance to elucidate the pathogenic mechanisms of IBD and for the development of diagnostic tools and of innovative therapeutics. The "Genomics" component of Core B will use complementary high throughput assays of chromatin status (FAIRE, and ChIP) and gene expression (RNA) from isolated single cells (murine and human), and clinically phenotyped pafients combined with deep sequencing. Each Project profits by centralized data processing and analysis that increases feasibility and efficiency, decreases costs for each Program Project investigator and limits variations that may occur from technical error. Furthermore, Core B capitalizes and builds on the financial commitments and technical expertise already made by the NIH (ENCODE, 1000 genomes, and HapMap projects) and the Carolina Center for Genome Sciences. Data generated by Core B will allow each investigator to study active regulatory elements in the genome at a level of detail yet to be performed.

核心B的主要目标是提供肠组织，分离的细胞群， 来自临床表征的IBD患者和健康对照的功能基因组信息。核心将 克服了使用动物模型的一个公认的障碍-指导动物研究， 这些问题将直接转化为人类IBD。数据和组织库以及新技术 通过这一核心开发将使研究人员有机会将分子发现与 人类疾病的模式物种。核心B将充分利用IBM的现有资源和专业知识。 已经建立了获取和处理手术切除和肠活检的基础设施。 核心B的“组织”组件将处理并提供冷冻肠组织; RNA和蛋白质提取物 从肠组织中，去识别疾病表型的临床信息，并应 invesfigators，分离的肠细胞群体。在需要时，核心将能够提供匹配的 外周血单个核细胞群中的血清以及DNA与免疫表型、临床 表型与遗传背景。了解人类IBD的分子基础还远未达到 办妥了一批高通量测定允许在异质性细胞中鉴定基因调控网络， 对于阐明IBD的致病机制以及对于研究IBD的发病机制， 诊断工具和创新疗法的发展。核心B的“基因组学”组件将使用 染色质状态（FAIRE和ChIP）和基因表达（RNA）的互补高通量测定 从分离的单细胞（鼠和人），和临床表型的患者结合深 测序每个项目都通过集中的数据处理和分析来提高可行性， 效率，降低每个计划项目调查员的成本，并限制可能发生的变化， 技术错误。此外，核心B利用和加强财政承诺和技术合作， 美国国立卫生研究院（ENCODE，1000个基因组和HapMap项目）和卡罗莱纳中心已经提供的专业知识 基因组科学。核心B生成的数据将允许每名研究者研究活性监管 基因组中的元素在一个细节的水平还有待执行。