Developmental Mechanisms of Human Idiopathic Scoliosis

项目概要/摘要（管理核心） 我们已经建立了一个创新的项目，题为"人类特发性 脊柱侧凸"。该计划结合了人类无偏见的基因发现，建模和基因发现， 斑马鱼，以及基因调控序列的基因组分析，这些基因调控序列定义了 青少年特发性脊柱侧凸（AIS）是儿童中最常见的肌肉骨骼疾病。三个研究 这些团体正在领导这些努力。项目1 "人类"专注于AIS基因发现，由Carol Wise领导， PD，PI，德克萨斯大学西南医学中心和德克萨斯苏格兰儿童医院。项目 2 "斑马鱼"是由华盛顿大学圣路易斯医学院的莱拉·索尔尼卡-克雷泽尔和她的合作者领导的， 调查员瑞恩·格雷博士德克萨斯大学项目3 "基因组学"由纳米比亚大学Nadav Ahituv领导。 加州旧金山弗朗西斯科。行政核心将协助该方案的活动，该方案已经是一个工作方案， 协作，并将最终负责其执行和生产力。项目总监怀斯博士， 核心管理员Liza Nowlin女士和门户网站管理员Kidane博士将监督管理工作 该计划。核心将促进组织、通信、数据流、合规性和生产力 在研究小组之间。核心的具体责任是确保有效和经常地 项目各组成小组之间的沟通，以虚拟方式或在线方式定期举行会议 人.这将包括与咨询委员会定期举行会议。会议的主要目的是 严格解释结果，确保质量控制，确定实现指定目标的进展，并与 咨询委员会。核心委员会将负责确认每个项目都有必要的资源， 确定实现特定目标的时间表，监控实现这些目标的进展，并帮助指导任何 必要的方案修改。我们合作的一个主要目标是产生知识、工具和资源， 将推动脊柱畸形研究领域向前发展。行政核心还将监督多组学的沉积 将编程数据导入SpineSource，这是在上一个授标周期中开发的一种新工具， 通信和数据共享。我们希望SpineSource不仅成为我们团队的重要资源， 以及脊柱和脊柱畸形领域的其他研究人员和利益相关者。否则，行政核心 将负责定期监测预算，确保资金得到适当支付， 遵守道德准则，遵守机构和联邦要求（如机构审查委员会， 机构动物护理和使用委员会），并与数据共享政策。最后，核心将促进 准备和提交手稿，确保与NIH公共获取政策的公平性和一致性。 通过这些方式，核心将促进计划内的协同互动，并加速破译目标。 AIS的发病机制。

PROJECT SUMMARY/ABSTRACT (ADMINISTRATIVE CORE) We have established an innovative Program entitled “Developmental Mechanisms of Human Idiopathic Scoliosis”. This program combines unbiased gene discovery in humans, modeling and gene discovery in zebrafish, and genomic analysis of gene regulatory sequences that are defining the underlying causes of adolescent idiopathic scoliosis (AIS), the most common musculoskeletal disorder in children. Three research groups are leading these efforts. Project 1 “Human” focuses on AIS gene discovery and is led by Carol Wise, PD, PI, University of Texas Southwestern Medical Center and Texas Scottish Rite Hospital for Children. Project 2 “Zebrafish” is led by Lila Solnica-Krezel, Washington University School of Medicine St. Louis, and her co- investigator Dr. Ryan Gray, University of Texas. Project 3 “Genomics” is led by Nadav Ahituv, University of California San Francisco. The Administrative Core will aid activities of the Program, which is already a working collaborative, and will be ultimately responsible for its execution and productivity. The Program Director Dr. Wise, the Core Administrator, Ms. Liza Nowlin, and web portal administrator Dr. Kidane will oversee the administration of the Program. The Core will facilitate organization, communication, data flow, compliance, and productivity between the research groups. Specific responsibilities of the Core will be to ensure effective and frequent communication between component groups of the project by hosting regular meetings either virtually or in person. These will include regular meetings with the Advisory Committee. Primary purposes of the meetings will be to rigorously interpret results ensuring quality control, identify progress toward specified goals, and to interact with the Advisory Committee. The Core will be responsible for confirming that requisite resources are available for each Project, defining timelines for achieving specified goals, monitoring progress toward those goals, and helping to guide any necessary programmatic changes. A major goal of our collaborative is to generate knowledge, tools, and resources that will spur the field of spine deformity research forward. The Administrative Core will also oversee deposition of multi-omics Programmatic data into SpineSource, a new tool that was developed in the prior award cycle to facilitate and centralize communication and data sharing. We expect that SpineSource will become an important resource for not only our team but other researchers and stakeholders in the area of spine and spinal deformity. Otherwise the Administrative Core will be responsible for regularly monitoring budgets and ensuring that funding is disbursed appropriately, and for compliance with ethical guidelines, with institutional and federal requirements (e.g. institutional review boards, institutional animal care and use committees), and with data-sharing policies. Finally, the Core will facilitate the preparation and submission of manuscripts, ensuring fairness and consistency with NIH public access policies. In these ways the Core will promote synergistic interaction within the Program and hasten the goal to decipher the pathogenesis of AIS.