Genomics Core

基因组学核心

• 批准号: 8326909
• 负责人: CHRISTOPHER H WOELK
• 金额: $ 24.12万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-08 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8326909
• 关键词: Animal Model; Animals; Binding; Bioinformatics; Biological; Biological Assay; Biological Markers; Biological Models; Biology; Brain; CD4 Positive T Lymphocytes; Cells; Chromatin Remodeling Factor; Complex; Coupled; DNA; DNA biosynthesis; Data; Defect; Evaluation; Experimental Designs; Gene Expression; Gene Expression Microarray Analysis; Gene Expression Profile; Gene Expression Regulation; Genes; Genome; Genomics; HIV; HIV-1; Highly Active Antiretroviral Therapy; Histone Deacetylase Inhibitor; Human; In Vitro; Individual; Infection; Instruction; Laboratories; Macaca mulatta; Maps; MicroRNAs; Microarray Analysis; Modeling; Molecular; Monitor; Ontology; Pathway interactions; Patients; Plasma; Preparation; Proteins; RNA; RNA Sequences; Research; Research Personnel; SIV; Sampling; Sequence Analysis; T memory cell; Technology; Testing; Therapeutic; Therapeutic Intervention; Tissues; Translational Research; Viral; Virus; Virus Latency; base; chromatin immunoprecipitation; collaboratory; in vitro Model; in vivo Model; nonhuman primate; novel; promoter; research study; tool

PROJECT SUMMARY (See instructions): The main objective of the Genomics Core will be to provide access to researchers on the collaborator to genomics technologies and the bioinformatic analysis needed to analyze the complex data derived from such technologies. Genomics technologies have become essential laboratory tools and will generate data that will guide the research in the collaboratory towards an HIV-1 cure. The Genomics Core will interact with every project in every objective and with the other cores proposed in the collaboratory. Specifically, with respect to virus genomics, the Genomics Core will provide access to sequencing, which will be used to identify the defects in proviral DNA that result in non-competent virus (Project 4.1) and will also be used to identify additional virus reservoirs by revealing viruses in the plasma whose sequence does not correlate with virus derived from the well-characterized CD4+ T cell reservoir (Project 4.2). Additionally, each project will benefit from the assays at the Genomics Core to monitor HIV replication in order to evaluate latency and the effects of HlV-inducing compounds. In respect to host genomics, the Genomics Core will primarily provide gene expression assays (whole genome microarray and qRT-PCR) in order to define the molecular mechanisms underlying viral persistence (Projects 1.1, 1.2,1.4 and 1.5) and determine biomarkers indicative of effective HlV-inducing compounds (Project 2.1). In addition, chromatin immunoprecipitation (ChIP) coupled with high throughput sequencing (ChlP-Seq) will be used to investigate gene regulation by the BAF chromatin remodeling complex (Project 1.2). When these studies are complete the genomics assays provided by the Genomics Core will have provided a better understanding of HIV latency, identified new pathways and avenues for therapeutic intervention, delineated the mode of action of HlV-inducing compounds, and characterized new viral reservoir in HIV-infected individuals.

项目总结（见说明）： 基因组学核心的主要目标是为合作者的研究人员提供基因组学技术和分析这些技术所产生的复杂数据所需的生物信息学分析。基因组学技术已成为实验室的基本工具，并将产生数据，指导合作实验室的研究工作，以治愈艾滋病毒1型。基因组学核心将与每个目标中的每个项目以及合作实验室中提出的其他核心进行交互。 具体而言，在病毒基因组学方面，Genomics Core将提供测序，用于鉴定导致非感受态病毒的前病毒DNA缺陷（项目4.1），还将用于通过揭示血浆中序列与来源于充分表征的CD 4 + T细胞储库的病毒不相关的病毒来鉴定其他病毒储库（项目4.2）。此外，每个项目将受益于基因组学核心的检测，以监测艾滋病毒复制，以评估潜伏期和艾滋病毒诱导化合物的影响。 关于宿主基因组学，基因组学核心将主要提供基因表达测定（全基因组微阵列和qRT-PCR），以定义病毒持久性的分子机制（项目1.1、1.2、1.4和1.5），并确定指示有效HIV诱导化合物的生物标志物（项目2.1）。此外，染色质免疫沉淀（ChIP）结合高通量测序（ChlP-Seq）将用于研究BAF染色质重塑复合物的基因调节（项目1.2）。 当这些研究完成时，由基因组学核心提供的基因组学测定将提供对HIV潜伏期的更好理解，确定用于治疗干预的新途径和途径，描绘HIV诱导化合物的作用模式，并表征HIV感染个体中的新病毒储库。