Preclinical Models Core

临床前模型核心

• 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
• 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

(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） 项目摘要 描述：临床前模型核心（PMC）支持IDDRC用户研究IDD病理生理学和/或 使用以下一个或两个临床前模型寻求IDD的新处理：（1）啮齿动物模型：此核心 组件可以帮助用户表征遗传或遗传模型中的行为表型 获得的疾病。在此核心中评估的主要行为领域包括：学习，记忆，社会 偏爱，沟通，运动功能和与情感障碍有关的行为； （2）人类IPSC模型： 该核心组件通过生成诱导的多能干细胞来帮助用户创建IDD的单元格模型 （IPSC）使用标准重编程技术或通过CRISPR-CAS9进行基因组编辑 IPSC线，然后分化为分子和细胞表型的神经元细胞类型 表征。这些单元格是从具有IDD的人类的，提供了一个模型，可以在其中可以 仔细检查遗传疾病的分子和细胞后果，并评估可能的效率 疗法。许多中心调查人员正在使用完整的模型系统，两者都使用 服务在一个领导下紧密互动。 PMC强调对用户及其员工的培训。受过训练的用户可以继续在自己的实验室学习， 或者他们可以以降低的成本利用PMC中的设备和/或试剂。 PMC提供的服务 所有其他中心核心提供的内容都完整，用户经常使用多个 完成项目的核心。此外，PMC与姐妹IDDRC的类似内核紧密相互作用以共享 协议，跨效率的结果度量，以提高IDDRC的严格性和可重复性 网络。 与IDDRC任务相关：PMC桥接“基因，大脑和行为”的所有三个领域，主题 CHOP/PENN IDDRC（总体请参见研究计划）。核心是根据用户调查而开发的 在2014年，强调需要以IDD为中心的设施来研究与IDD相关的行为和细胞 在IDD临床症状的背景下的表型，并利用IPSC潜力获得见解 与其他核心以合作的方式进入IDD的病理生理学和改善治疗 IDDRC。 资格：这些服务既可以用于批准的IDDRC的用户，也可以使用 网络中的其他中心。