Washington University Intellectual and Developmental Disabilities Research Center

华盛顿大学智力与发育障碍研究中心

• 批准号: 10085124
• 负责人: JOHN N. CONSTANTINO
• 金额: $ 124.46万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-28 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10085124
• 关键词: Affect; Animal Model; Behavior; Behavioral; Biocompatible Materials; Bioinformatics; Biological Markers; Biological Models; Brain; Brain imaging; Caliber; Cell Line; Cell model; Cells; Child; Clinical; Clinical Trials; Collection; Communities; Core Facility; Data; Data Set; Derivation procedure; Development; Developmental Disabilities; Disease; Down Syndrome; Electronic Health Record; Enrollment; Equipment and supply inventories; Etiology; Extramural Activities; Faculty; Familial disease; Family; Functional disorder; Funding; Gene Dosage; Generations; Genes; Genetic; Genomics; Goals; Human; Image; Individual; Infant; Infrastructure; Institutes; Institution; Intellectual and Developmental Disabilities Research Centers; Intellectual functioning disability; Interruption; Intervention; Investigation; Knowledge; Longitudinal Studies; Methods; Molecular; Mothers; Mutation; Natural History; Neurodevelopmental Disability; Neurosciences; Pathogenesis; Pathway interactions; Patients; Phase; Phenotype; Population; Prevention; Preventive Intervention; Quality of life; Registries; Research; Research Infrastructure; Research Personnel; Research Project Grants; Resources; Risk; Rodent Model; Science; Scientist; Specialized Center; Standardization; Structure; Synapses; Syndrome; Therapeutic; To specify; Translating; Translational Research; Translations; United States National Institutes of Health; Universities; Variant; Washington; autism spectrum disorder; base; behavioral genomics; behavioral phenotyping; cognitive neuroscience; cohort; follow-up; frontier; functional genomics; gene discovery; genetic variant; imaging study; medical schools; multiple omics; neuroimaging; new therapeutic target; novel; novel therapeutics; patient population; premature; prevent; programs; prospective; psychosocial; relating to nervous system; success; synergism; working group

Overall Project Abstract For the third cycle of the Intellectual and Developmental Disabilities Research Center at Washington University, we propose a next phase in a comprehensive approach to understanding, ameliorating, and/or preventing neurodevelopmental disability through translational scientific investigation at the respective levels of cell, synapse, circuit, and behavior, capitalizing upon major strengths of WUSTL in genomics, behavioral/cognitive neuroscience, and clinical-translational science. The overarching goals of our Center are as follows: (1) To sustain and evolve an integrated structure of core scientific facilities that occupy a critical niche in the scientific community, attract and support highly-qualified investigators, and facilitate high-caliber, translational research on the pathogenesis and treatment of IDDs. In this application we propose specific enhancements to each of our scientific core facilities: an expanded technical team for the Developmental Neuroimaging Core, a dedicated cellular models unit within the Model Systems Core (methods calibrated with a cross-IDDRC working group for cellular models of IDD co-led by the IDDRC@WUSTL), and a new clinical trials / natural history studies unit within the Clinical-Translational Core (CTC). The CTC will continue to facilitate the collection and interpretation of genomic, phenotypic, environmental and biomarker data across generations, and promote step-wise translation of new discoveries on risk and pathogenesis to higher-impact interventions for patients. The IDDRC@WUSTL will provide critical infrastructure for research efforts that have created synergies with other intramural and extramural Centers/Institutes, including a newly-funded in-depth longitudinal study of infants born to mothers enrolled in the March of Dimes Prematurity Research Center Cohort, the launch of a prospective replication cohort for the Infant Brain Imaging Study of Autism (IBIS), two multisite initiatives in Down Syndrome, and an NIH Autism Center of Excellence Network in gene discovery. (2) To cultivate nodes of new interdisciplinary scientific activity within the Center, in frontiers of IDD research which are critical for the derivation of higher-impact treatment and preventive intervention, along the Center’s four major themes: (i) the prevention of prematurity and its neurodevelopmental consequences; (ii) the identification of intermediate phenotypes in the development of IDD; (iii) structural and functional characterization of the developing human brain, and (iv) functional genomics relevant to IDD pathogenesis. In this cycle we will build on prior successes in cultivating a dynamic, interactive, and productive community of scientists engaged in IDD-science, challenging itself to generate and harness new knowledge toward translational advances in therapeutics and prevention. (3) To conduct a signature research project that represents a bold, critical step toward higher-impact intervention for IDD. In this project, a novel platform for standardizing multi-omic characterization of the consequences of variation in gene dosage will be implemented across dozens of isogenic cell lines, each representing haploinsufficiency in a different high-confidence IDD-related gene, to identify convergent mechanisms of IDD.

总体项目摘要 对于华盛顿大学智力和发展障碍研究中心的第三个周期， 我们以全面的理解，改善和/或阻止的全面方法提出下一阶段 神经发育障碍通过在各个细胞水平上的转化科学研究， 突触，电路和行为，利用WUSTL在基因组学，行为/认知方面的主要优势 神经科学和临床翻译科学。我们中心的总体目标如下：（1） 维持和发展核心科学设施的综合结构，该设施占据了科学的关键利基市场 社区，吸引和支持高度合格的研究人员，并促进高素质的翻译研究 关于IDD的发病机理和治疗。在此应用程序中，我们对我们的每个人提出了特定的增强 科学核心设施：一个扩展的发展神经影像核的技术团队，一个专门的 模型系统核心内的蜂窝模型单元（用交叉IDDRC工作组校准的方法 IDDR@wustl共同主导的IDD的蜂窝模型和一个新的临床试验 /自然历史研究单元 在临床翻译核心（CTC）内。 CTC将继续促进收集和解释 几代人的基因组，表型，环境和生物标志物数据，并促进逐步促进 对患者的风险和发病机理的新发现转化为更高影响的干预措施。这 IDDRC@wustl将为研究工作提供关键的基础架构 壁内和壁外中心/机构，包括对婴儿的新资助的深入纵向研究 向参加Dimes早产研究中心队列的招生的母亲，成为潜在的 婴儿脑成像研究（IBIS）的复制队列（IBIS），两项唐氏综合症的多站点倡议， 以及NIH自闭症基因发现卓越网络。 （2）培养新的节点 中心内的跨学科科学活动，在IDD研究的边界，这对于推导至关重要 沿该中心的四个主要主题进行更高影响的治疗和预防干预：（i）预防 早产及其神经发育后果； （ii）鉴定中间表型 IDD的发展； （iii）发展中脑的结构和功能表征，（iv） 功能基因组学与IDD发病机理有关。在这个周期中，我们将以先前的成功来培养 从事IDD科学的科学家的动态，互动和产品社区，挑战 产生和利用新知识，以转化治疗和预防方面的转化进展。 （3）到 进行签名研究项目，代表了朝着更高影响干预的大胆而关键的一步 IDD。在这个项目中，一个新颖的平台，用于标准化多摩尼克的后果 基因剂量的变化将在数十个等生细胞系中实施，每种代表 在不同的高信心IDD相关基因中，单倍不足，以识别IDD的收敛机制。