Functional Genomics

功能基因组学

• 批准号: 9982412
• 负责人: Anny Xiaobo Zhou
• 金额: $ 46.01万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9982412
• 关键词: Affinity Chromatography; Airway Disease; Asthma; Biological; Biological Assay; Biology; Bronchoscopy; Candidate Disease Gene; Cell model; Cells; Cellular biology; Chromatin Structure; Chronic Obstructive Airway Disease; Chronic lung disease; Code; Collection; Consensus; Consult; Critical Care; DNA; Data; Diamond; Disease; Dissection; Ensure; Epigenetic Process; Epithelial Cells; Equipment; Gene Silencing; Genes; Genetic; Genomic Segment; Genomics; Goals; Hospitals; Human; Human Biology; Human Cell Line; Human Genetics; Human Resources; In Vitro; Information Resources; Intercistronic Region; Knowledge; Laboratories; Link; Lung; Lung diseases; Maps; Mass Spectrum Analysis; Medicine; Methodology; Methods; MicroRNAs; Modeling; Molecular; Molecular Biology; Network-based; Pathway interactions; Phenotype; Play; Principal Investigator; Productivity; Program Research Project Grants; RNA Interference; Research Assistant; Research Personnel; Resources; Risk Factors; Role; Sampling; Series; Services; Speed; Standardization; Supervision; Systems Biology; Time; Training; Translating; Untranslated RNA; Validation; Variant; Woman; Work; airway epithelium; airway obstruction; asthma model; base; bronchial epithelium; causal variant; cigarette smoke-induced; cost; experience; functional genomics; gene function; genetic variant; genome wide association study; human genomics; in vivo; loss of function; methylome; network models; novel; programs; screening; therapeutic target

ABSTRACT The goal of this integrative program project grant, “Systems Biology of Airway Disease”, is to identify the shared genetic, genomic and epigenetic features between asthma and COPD, two of the most common chronic lung diseases. Aiming to translate human genetics and genomics to biology and eventually benefit disease treatment, this PPG differs from other systems biology proposals because of its comprehensive functional assessment pipelines, which include a series of functional validations on genetic variants, candidate genes and network modules shared between asthma and COPD. Such functional validation will greatly speed up and prioritize candidate disease genes as therapeutic targets. Core C will provide overall functional support to all projects in this PPG. The function of Core C includes: (1) identifying functional GWAS and sequencing variants that are associated with airflow obstruction in both asthma and COPD (Project 1); (2) experimentally validating disease modules built upon genetics, genomics and epigenetics from asthma and COPD subjects (Projects 1,2 and 3); (3) establishing a cellular phenotypic screening model that is relevant to asthma and COPD and applying loss-of-function approach by RNAi in this model to assess novel disease genes (Project 2 and 3); (4) modeling cigarette smoke induced DNA methylome changes in primary human bronchial epithelial cells (Project 3). We will provide needed biological consulting and support to all projects. To fulfill these functions of Core C and, thus, ensure successful completion of this PPG, Core C is assembled with three senior research assistants directed by the experienced cell biologist, Dr. Anny Xiaobo Zhou, the Director of Functional Genomics Laboratory who will be assisted by Dr. Mark Perrella, a senior molecular biologist and pulmonologist in the Division of Pulmonary and Critical Care Medicine at Brigham and Women's Hospital, and a longtime collaborator of Dr. Zhou and several other key investigators of the PPG. Core C is based on a well- equipped molecular and cell biology laboratory that has access to all needed resources. In addition, Dr. Zhou has been a longtime collaborator of all Project Principal Investigators, Drs. Scott Weiss, Benjamin Raby and Dawn DeMeo. They have a demonstrated successful track record and productivity that will ensure Core C will meet the overall functional needs of this PPG.

抽象的 综合计划项目赠款“气道疾病的系统生物学”的目标是确定您 哮喘和COPD之间共享的遗传，基因组和表观遗传特征，这是两个最常见的 慢性肺部疾病，旨在将人类遗传学转化为生物学 疾病治疗，该PPG与其他系统的生物学建议不同 功能评估管道，其中包括有关遗传变异的一系列功能验证，候选者 哮喘和COPD共享的基因和网络模块将大大速度 将候选疾病基因作为治疗靶标提供优先级。 对于此PPG中的所有项目。 与哮喘和COPD中的气流阻塞相关的变体（项目1）； 从哮喘和COPD受试者的遗传学，基因组学和表观遗传学基础上验证疾病模块 （项目1,2和3）； COPD和RNAi在该模型中应用功能丧失方法来评估新型疾病（项目2 3）;（4）烟雾诱导的DNA甲基机的原发性支气管上皮变化 细胞（项目3）。 核心C的功能，从而确保该PPG的成功压缩，核心核心核心核心核心核心核心核心核心核心核心核心核心核心核心核心核心核心核心核心核心核心核心核心核心核心核心核心核心核心核心核心核心核心核心 经验丰富的细胞生物学家主任Anny Xiaobo Zhou博士主任的高级研究助理 功能性基因组学实验室将由高级分子生物学家马克·佩雷拉（Mark Perrella）博士协助 Brigham和妇女医院的肺和重症监护医疗疗法肺科医生， 周开博士的长期合作者和PPG的其他几个关键调查员。 设备的分子和细胞生物学实验室，还需要所有需要资源的资源。 一直是所有项目项目项目首席调查员Scott Weiss，Benjamin Raby和 黎明德姆（Dawn Demeo）。 满足该PPG的总体功能需求。