Model Systems Core

模型系统核心项目摘要/摘要 模型系统核心（MSC）将利用华盛顿大学学院的机构优势 在遗传学，神经科学，生物信息学和神经影像学的医学（WUSM），以解决关键 关于缺碘症的病因和治疗方法的问题，特别是关于遗传异常和 环境因素MSC将被组织成两个单位-细胞模型单位（CMU）和 动物评估单位（AAU），后者由三个分单位组成，包括动物 行为、神经病理学和神经生理学。通过其互动科学家团队，MSC将 通过提供无缝的专业知识，资源和评估来实现其特定目标， WUSM研究人员的目的是：（1）促进基础分子和细胞的发现 IDD的不同原因共享的途径;（2）确定与IDD相关的神经信号， 神经回路水平和全脑水平;（3）IDD的核心神经行为特征， 阐明其因果根源;（4）制定干预措施，以改善遗传或 环境对大脑发育的影响。为了实现这些目标，MSC将使用一个集成的 模型系统方法，以协同其自身单位以及临床单位的优势 翻译核心和发育神经影像核心。每个单位的其他目标也将是 操作。例如，人类疾病的重编程体细胞模型提供了基本的 深入了解生物途径以及疾病过程;因此，MSC现在将提供 可更新的源自患者的人类IDD细胞模型，以将遗传改变与疾病联系起来 机制和表型通过CMU。海安会还将继续提供咨询和 IDD动物模型脑结构、病理、生理和行为的综合评价 通过AAU。跨核心，CMU将与临床翻译核心密切合作， 人类基因组表征单位，以开发IDD患者登记册，将直接用作 招募来源，用于推导患者来源的细胞模型。同样，分配数量单位取决于 发育神经影像学核心，用于对相关临床前模型进行成像，以研究机制 潜在的发育病理学可能为临床研究提供桥梁。使用这些 MSC的首要使命是确定新的治疗方法、生物标志物和/或 采取干预措施，预防或减少与缺碘相关疾病的影响。随着更多的基因组数据 WU调查人员利用这些信息，这是MSC的另一个关键角色 将是跨IDDRC@WUSTL核心和其他核心的新信息和现有信息的集成。 大学内的现有设施。

Model Systems Core Project Summary/Abstract The Model Systems Core (MSC) will leverage the institutional strengths of Washington University School of Medicine (WUSM) in genetics, neuroscience, bioinformatics and neuroimaging to address key questions on the causes and treatments of IDD with particular reference to genetic abnormalities and environmental factors. The MSC will be organized into two units – the Cellular Models Unit (CMU) and the Animal Assessments Unit (AAU), the latter being composed of three subunits including Animal Behavior, Neuropathology, and Neurophysiology. Through its team of interactive scientists, the MSC will pursue its specific aims by providing seamless expertise, resources, and assessments to committed WUSM investigators for the purpose of: (1) promoting the discovery of the basic molecular and cellular pathways shared by diverse causes of IDD; (2) determining the neural signatures associated with IDD at the neural circuit level and whole brain; (3) characterizing core neurobehavioral features of IDD and clarifying their causal origins; and (4) developing interventions to ameliorate the effects of genetic or environmental insults on the developing brain. To achieve these goals, the MSC will use an integrated model systems approach to synergize the strengths of its own units as well as those of the Clinical Translational Core and the Developmental Neuroimaging Core. Additional aims for each unit will also be operative. For example, reprogrammed somatic cell models of human disorders provide fundamental insights into biological pathways as well as disease processes; therefore, the MSC will now offer renewable patient-derived human IDD cellular models to link genetic alterations with disease mechanisms and phenotype via the CMU. The MSC will also continue to provide consultation and comprehensive assessment of brain structure, pathology, physiology and behavior of IDD animal models through the AAU. Reaching across cores, the CMU will work closely with the Clinical Translation Core’s human genomic characterization unit to develop IDD patient registries that will be directly used as a recruitment source for derivation of patient-derived cellular models. Similarly, the AAU depends upon the Developmental Neuroimaging Core for imaging relevant preclinical models to investigate mechanisms underlying developmental pathology potentially providing a bridge to clinical studies. Using these strategies, the overarching mission of the MSC is to identify new treatments, biomarkers and/or interventions that can prevent or reduce the impact of IDD-linked diseases. As more genomic data becomes available and WU investigators capitalize on this information, another critical role for the MSC will be the integration of new and existing information across the IDDRC@WUSTL cores and other existing facilities within the University.