Preclinical Models Core

临床前模型核心

基本信息

批准号：
10450698
负责人：
Zhaolan Zhou
金额：
$ 17.47万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
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/10450698
关键词：
3-Dimensional Affect Anxiety Articulation Behavior Behavioral Biological Assay Biological Models Biometry Blood Brain CRISPR/Cas technology Cell Line Cell model Cells Clinical Communication Communities Consultations Data Data Analyses Data Collection Data Science Core Development Disease Education Eligibility Determination Equipment Experimental Designs Exposure to Fibroblasts Functional disorder Genes Genetic Genetic Diseases Genetic Models Human Immunotherapy In Vitro Intellectual and Developmental Disabilities Research Centers Laboratories Leadership Learning Lifestyle-related condition Maintenance Measures Memory Methodology Methods Microdissection Mission Modeling Molecular Monitor Mood Disorders Motor Motor Activity Mutation Neurons Organoids Outcome Measure Pathway interactions Patients Performance Peripheral Persons Pharmaceutical Preparations Phenotype Pluripotent Stem Cells Pre-Clinical Model Procedures Production Protocols documentation Reagent Reflex action Reproducibility Research Research Personnel Rodent Rodent Model Serum Services Sister Social Interaction Somatic Cell Stimulus Structure Surveys Symptoms System Techniques Technology Testing Therapeutic Intervention Tissue Harvesting Training Treatment Efficacy Ultrasonics Validation Variant Viral Virus base behavior test behavioral phenotyping brain behavior cell type community center cost data integration design disability effective therapy efficacy evaluation experimental study genome editing genomic data human subject improved induced pluripotent stem cell insight interest member mouse model neural circuit neurobiological mechanism neuroimaging neuromuscular novel pre-clinical assessment preference response social stem cell model vocalization working group

项目摘要

(CORE F – PMC: PRECLINICAL MODELS CORE) PROJECT SUMMARY Description: The Preclinical Models Core (PMC) supports IDDRC users who study IDD pathophysiology and/or seek new treatments for IDD using one or both of the following preclinical models: (1) Rodent models: This Core component assists users with the characterization of behavioral phenotypes in mouse models of genetic or acquired disabilities. Major behavioral domains assessed in this core include: learning, memory, social preference, communication, motor function, and affective disorder-related behaviors; (2) Human iPSC models: This Core component assists users to create cell models of IDD by generating induced pluripotent stem cells (iPSCs) using standard reprogramming technologies or by genome editing via CRISPR-Cas9 on established iPSC lines, followed by differentiation into neural cell types of interest for molecular and cellular phenotype characterization. These cells, some derived from humans with IDDs, provide a model in which it is possible to scrutinize molecular and cellular consequences of genetic disease and to evaluate the efficacy of possible therapies. The complementary model systems are being used by many of the center investigators, and the two services interact closely under one leadership. The PMC emphasizes training of users and their staff. Trained users can continue studies in their own laboratory, or they can utilize the equipment and/or reagents in the PMC at reduced cost. The services offered by the PMC are complementary to those offered by all of the other center cores, and users frequently use more than one core to complete a project. In addition, the PMC interacts closely with similar cores at sister IDDRCs to share protocols, cross-validate outcome measures, in order to improve rigor and reproducibility across the IDDRC network. Relevance to IDDRC Mission: The PMC bridges all three domains of “Genes, Brain, and Behavior”, the theme of the CHOP/Penn IDDRC (see Research Plan Overall). The Core was developed in response to a user survey in 2014 that emphasized a need for an IDD-focused facility to study IDD-related behavioral and cellular phenotypes in the context of IDD clinical symptoms and to take advantage of the iPSC potentials to gain insights into disease pathophysiology and improve treatment for IDDs in a collaborative manner with other Cores of this IDDRC. Eligibility: These services are available both to approved users of the IDDRC at CHOP/Penn and to users at other Centers in the Network.

（核心 F – PMC：临床前模型核心）项目概要描述：临床前模型核心 (PMC) 支持研究 IDD 病理生理学和/或使用以下一种或两种临床前模型寻求 IDD 的新治疗方法： (1) 啮齿类动物模型：此核心组件可帮助用户表征遗传或小鼠模型中的行为表型该核心评估的主要行为领域包括：学习、记忆、社交。（2）人类iPSC模型：偏好、沟通、运动功能、情感障碍相关行为；该核心组件通过生成诱导多能干细胞来帮助用户创建 IDD 细胞模型 (iPSC) 使用标准重编程技术或通过 CRISPR-Cas9 进行基因组编辑 iPSC 系，然后分化为分子和细胞表型感兴趣的神经细胞类型这些细胞（其中一些来自患有IDD的人）提供了一个模型，可以在其中进行表征。仔细检查遗传疾病的分子和细胞后果，并评估可能的疗效许多中心研究人员正在使用互补模型系统，并且这两个疗法。服务在一个领导下密切互动。 PMC强调对用户及其员工的培训。经过培训的用户可以在自己的实验室继续研究，或者他们可以以较低的成本使用 PMC 中的设备和/或试剂 PMC 提供的服务。与所有其他中心核心提供的功能相辅相成，用户经常使用多个中心核心此外，PMC 还与姊妹 IDDRC 的类似核心进行密切互动，以实现共享。协议，交叉验证结果测量，以提高整个 IDDRC 的严谨性和可重复性网络。与 IDDRC 使命的相关性：PMC 连接了主题“基因、大脑和行为”的所有三个领域 CHOP/Penn IDDRC（请参阅总体研究计划）的核心是根据用户调查而开发的。 2014 年强调需要建立一个以 IDD 为重点的机构来研究 IDD 相关的行为和细胞 IDD 临床症状背景下的表型，并利用 iPSC 潜力获得见解与该领域的其他核心合作，深入研究疾病病理生理学并改善 IDD 的治疗 IDDRC。资格：这些服务既适用于 CHOP/Penn 的 IDDRC 批准用户，也适用于以下机构的用户：网络中的其他中心。