Functional Genomics

摘要 这个综合项目的目标，项目赠款，“系统生物学的气道疾病”，是确定 哮喘和COPD之间共有的遗传、基因组和表观遗传特征， 慢性肺部疾病旨在将人类遗传学和基因组学转化为生物学， 疾病的治疗，这个PPG不同于其他系统生物学的建议，因为它的全面性， 功能评估管道，其中包括一系列对遗传变异的功能验证， 哮喘和COPD之间共有的基因和网络模块。这种功能验证将大大加快 将候选疾病基因作为治疗靶点。核心C将提供整体功能支持 在这个PPG的所有项目。Core C的功能包括：（1）鉴定功能性GWAS并测序 与哮喘和COPD气流阻塞相关的变异（项目1）;（2）实验性 验证建立在哮喘和COPD受试者遗传学、基因组学和表观遗传学基础上的疾病模块 （项目1、2和3）;（3）建立与哮喘相关的细胞表型筛选模型， COPD和在该模型中应用RNAi的功能丧失方法来评估新的疾病基因（项目2 和3）;（4）模拟香烟烟雾诱导的原代人支气管上皮细胞DNA甲基化组变化 细胞（项目3）。我们将为所有项目提供所需的生物咨询和支持。满足这些 核心C的功能，从而确保成功完成这一PPG，核心C组装有三个 高级研究助理，由经验丰富的细胞生物学家Anny Xiaobo Zhou博士指导， 功能基因组学实验室将由高级分子生物学家Mark Perrella博士协助， 布里格姆妇女医院肺部和重症监护医学科的肺病学家， 周博士和PPG的其他几位主要研究人员的长期合作者。核心C是基于一个良好的- 配备了分子和细胞生物学实验室，可以获得所有需要的资源。此外，周博士 一直是所有项目主要研究者的长期合作者，斯科特韦斯博士，本杰明·拉比和 道恩·德梅奥他们有一个成功的业绩记录和生产力，将确保核心C将 满足本PPG的整体功能需求。

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.