IDD Models Core

IDD 模型核心

基本信息

批准号：
10239780
负责人：
John P Svaren
金额：
$ 19.15万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-15 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10239780
关键词：
3-Dimensional Affect Anatomy Animal Model Basic Science Behavioral Biological Markers Biotechnology Brain Cell Culture Techniques Cells Coculture Techniques Cognition Cognitive Complex Comprehensive Cancer Center Defect Development Diagnosis Disease Electrophysiology (science)Ensure Epigenetic Process Fostering Generations Genes Genetic Genomics Goals Human Human Resources Image Individual Infrastructure Institution Intellectual and Developmental Disabilities Research Centers International Investments Libraries Methods Microscopy Modeling Modification Molecular Molecular Analysis Molecular Biology Molecular and Cellular Biology Mus Mutation Nervous System Physiology Nervous system structure Neurodevelopmental Disorder Neurons Neurophysiology - biologic function Neurosciences Pathogenesis Pathway interactions Patients Pharmaceutical Preparations Phenotype Physiology Rattus Reproducibility Research Research Personnel Resources Rodent Rodent Model Service delivery model Services Signal Transduction Site Structure Study models Supervision Systems Analysis Techniques Technology Tissues Training Translational Research base behavior test behavioral phenotyping cell type design disease mechanisms study disease phenotype epigenomics experimental study genome editing human embryonic stem cell human pluripotent stem cell human stem cells induced pluripotent stem cell innovation meetings model development multilevel analysis nervous system development neurodevelopment novel novel strategies novel therapeutic intervention peer preclinical study screening small molecule stem cell model testing services therapeutic candidate tool translational approach translational study

项目摘要

The IDD Models Core is designed to foster development and analysis of human stem cell and rodent models of IDD conditions. The core supports basic science studies of molecular pathways and cellular interactions that are altered in genetic and epigenetic disorders affecting nervous system function. In addition, the core enables drug and biomarker studies, as well as preclinical studies that are aimed at developing novel translational approaches to IDD. A historic strength of the IDD Models core is the use of human pluripotent stem cell (hPSC)-based models, which include both patient-specific induced pluripotent stem cells (iPSCs) and their modification by genome editing, to study diverse types of IDD conditions. The core has incorporated novel approaches to meet the increased demands for rigor and reproducibility by meeting international/peer institution standards in the creation and characterization of patient-specific iPSCs and hESCs. The refined gene editing capabilities develop innovative cellular tools for sophisticated analysis of altered nervous system development and function. These models also provide the means to evaluate candidate therapeutics in disorder-relevant cells, as well as develop novel screens to identify promising compounds in small- and large-scale library screening. The core also empowers analysis of rodent models of IDD conditions, not only by providing support for their creation, but also by providing a comprehensive and cutting edge behavioral testing service. The service incorporates a battery of cognitive/nervous system analyses under the supervision of a skilled core manager to ensure the rigor and reproducibility of these IDD model studies. Our specific aims for the next project period are: (1) to create and analyze human stem cell models of IDD; and (2) to create and analyze rodent models of IDD. Recognizing that sophisticated analysis of these models is required to elucidate pathogenesis and novel therapeutic approaches, the IDD Models Core uses extensive on-site research resources and leverages an extended network of complementary research cores on the UW- Madison campus to provide the infrastructure and skilled personnel that support integrated analysis at molecular, genomic, epigenomic, cellular, electrophysiological, and behavioral levels. Assembly of these diverse resources is designed to broaden the scope and depth of IDD model studies and to facilitate progress of IDD research from basic science to translational studies.

IDD模型核心旨在促进人类干细胞的开发和分析和分析 IDD条件的啮齿动物模型。核心支持分子途径的基础科学研究以及影响神经的遗传和表观遗传疾病改变的细胞相互作用系统功能。此外，核心启用药物和生物标志物研究以及临床前研究旨在为IDD开发新型翻译方法的研究。历史优势 IDD模型核心是使用人多能干细胞（HPSC）模型的使用，包括患者特异性诱导的多能干细胞（IPSC）及其通过基因组编辑，研究不同类型的IDD条件。核心已纳入小说通过开会来满足对严格和可重复性的增加的方法国际/同伴机构在创建和特定于患者的特征方面的标准 IPSC和hESC。精致的基因编辑功能开发了创新的蜂窝工具神经系统发展和功能改变的复杂分析。这些模型也是如此提供评估与疾病相关的细胞中的候选治疗方法的方法，以及开发新颖的屏幕以识别小规模和大型库中有希望的化合物筛选。核心还使IDD条件的啮齿动物模型分析不仅是为他们的创造提供支持，也可以通过提供全面而最先进的优势行为测试服务。该服务包含了一系列认知/神经系统在熟练的核心经理的监督下进行分析，以确保严格性和可重复性这些IDD模型研究。我们在下一个项目期间的具体目标是：（1）创建和分析IDD的人类干细胞模型；（2）创建和分析IDD的啮齿动物模型。认识到需要对这些模型进行复杂分析以阐明发病机理以及新型的治疗方法，IDD模型核心使用广泛的现场研究资源和利用UW-的扩展互补研究核心网络麦迪逊校园提供支持集成的基础设施和熟练人员分子，基因组，表观基因组，细胞，电生理和行为水平的分析。这些不同资源的组装旨在扩大IDD模型的范围和深度研究并促进IDD研究从基础科学到转化研究的进步。