Core C - Model Systems Core

核心 C - 模型系统核心

• 批准号: 9750217
• 负责人: DAVID FRANCIS WOZNIAK
• 金额: $ 22.4万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2020-07-27
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9750217
• 关键词: Advisory Committees; Animal Behavior; Animal Model; Behavior; Behavioral; Bioinformatics; Biological; Biological Markers; Biological Models; Brain imaging; Caenorhabditis elegans; Cell model; Clinical; Complement; Consultations; Development; Developmental Biology; Disease; Drosophila genus; Electroencephalography; Emotional; Evaluation; Fragile X Syndrome; Genes; Genetic; Goals; Histologic; Human; In Vitro; Individual; Intellectual functioning disability; Intervention; Learning; Magnetic Resonance Imaging; Memory; Mental Depression; Mental Retardation and Developmental Disabilities Research Centers; Microscopy; Modeling; Motivation; Motor; Mus; Needs Assessment; Neurologic Deficit; Neurosciences; Pathogenicity; Pathology; Pathway interactions; Phenotype; Polysomnography; Premature Birth; Preventive Intervention; Procedures; Rattus; Research; Research Personnel; Resources; Rodent Model; Scientist; Sensorimotor functions; Sensory; Services; Sirolimus; Social Interaction; Somatosensory Evoked Potentials; Syndrome; Techniques; Testing; Therapeutic Intervention; Time; Universities; Zebrafish; animal imaging; autism spectrum disorder; career; channel blockers; clinical phenotype; experimental study; functional loss; human disease; human model; in vivo; insight; large-conductance calcium-activated potassium channels; neuropathology; neurophysiology; non-invasive imaging; novel; novel therapeutics; optical imaging; premature; relating to nervous system; screening; therapy development

Model Systems Core Project Summary Animal models are revolutionizing our understanding of IDDs, and such models provide fundamental insights into biological pathways and often display phenotypes that are similar to clinical indicators of the human disease, providing an opportunity to deduce mechanisms of disease pathology, and also to develop therapies. The Model Systems Core (MSC) is organized into three units – the Animal Behavior Unit, the Neuropathology Unit, and the Functional Assessments Unit. The goal of the MSC is to provide expertise, resources, and assessment to Center investigators involved in the creation and evaluation of animal and cellular models relevant to IDD, drawing on strengths in genetics, brain imaging, bioinformatics, and neuroscience to provide advice, assistance, and services to investigators at all career stages. The specific aims are: 1) Provide consultation to investigators needing assessments in animal behavior, pathology and CNS function. A priority for the Core Directors and Unit leaders is to make certain that first-time users are guided to appropriate services and understand the complement of available resources; 2) Characterize neurological deficits in rodent and cellular models of IDD submitted by investigators. The MSC is configured to provide access to a range of experimental approaches including: i) functional phenotyping of mice and rats (learning and memory, motor/sensorimotor functions, alterations in emotionality/motivation, social interactions, sensory behavioral functions, depression-like behaviors, and behaviors related to models of Autism Spectrum Disorder; ii) histological services to evaluate IDD-related changes at the cellular level; and, iii) sophisticated, non- invasive imaging (MRI, functional connectivity optical imaging) as well as in vitro (including advanced microscopy of cellular models) and in vivo neurophysiological assessments, such as electroencephalography (EEG), polysomnography, and somatosensory evoked potentials in animal models of IDD; 3) Assess novel therapies and/or biomarkers in models of IDD in animal behavior, pathology and CNS function. Each Unit within the MSC is already configured to allow rapid, sensitive testing of novel therapies and/or biomarkers for IDD models; 4) Integrate information across units, cores and other existing facilities within the University. Together with the Unit leaders, MSC Directors will provide guidance for institutional resources both within and outside of the MSC. Together with the Scientific Advisory Panel, MSC Directors will also help investigators identify the best model system for a specific gene locus, clinical phenotype and/or screening for compounds to reverse disrupted function. WUSTL has state-of-the-art expertise and facilities for zebrafish, C. elegans, and/or Drosophila models of human disease.

模型系统核心项目摘要 动物模型正在彻底改变我们对IDDS的理解，这些模型提供了基本的见解 并经常表现出与人类临床指标相似的表型 为推断疾病的病理机制以及开发治疗方法提供了机会。 模型系统核心(MSC)被组织成三个单元--动物行为单元、神经病理学 该股和职能评估股。MSC的目标是提供专业知识、资源和 对参与动物和细胞模型创建和评估的中心研究人员的评估 与IDD相关，利用遗传学、脑成像、生物信息学和神经科学的优势提供 在职业生涯的各个阶段为调查人员提供建议、帮助和服务。具体目标是：1)提供 咨询需要评估动物行为、病理学和中枢神经系统功能的研究人员。一个 核心主管和单位领导的首要任务是确保首次使用的用户得到适当的指导 提供服务并了解可用资源的补充性；2)描述 研究人员提交的IDD啮齿动物和细胞模型。MSC被配置为提供对 一系列实验方法，包括：i)小鼠和大鼠的功能表型(学习和 记忆、运动/感觉运动功能、情绪性/动机的改变、社会互动、感觉 行为功能、抑郁样行为和自闭症谱系障碍模型相关行为； 二)在细胞层面评估缺碘相关变化的组织学服务；和，三)复杂的、非 侵入性成像(MRI、功能连接光学成像)以及体外成像(包括高级 细胞模型的显微镜)和体内神经生理学评估，如脑电图学 IDD动物模型的脑电、多导睡眠图和体感诱发电位；3)评估新的 IDD动物行为、病理和中枢神经系统功能模型的治疗和/或生物标志物。每个人 MSC内的单元已经被配置为允许对新疗法和/或生物标记物进行快速、灵敏的测试 对于IDD模型；4)集成跨单元、核心和内部其他现有设施的信息 大学。MSC主任将与单位领导一起为机构资源提供指导 在MSC内部和外部。与科学顾问小组一起，MSC主任也将提供帮助 研究人员确定了特定基因座、临床表型和/或筛查的最佳模型系统 能逆转紊乱功能的化合物。WUSTL拥有最先进的斑马鱼专业知识和设施，C. 线虫和/或果蝇的人类疾病模型。