UCLA IDDRC

这项提案要求为加州大学洛杉矶分校的智力和发育障碍者提供5年的额外资金 研究中心(IDDRC)。40多年来，我们的使命一直是为 对智力和发育障碍的潜在机制进行多学科研究 (IDDS)，将这些发现转化为IDDS的有效治疗方法，并将这些发现传播给 科学界和公众。这份意见书扩展了我们5年前开始的翻译重点 更强调人体研究和临床试验，并与社区建立更紧密的联系。每一个 这5个核心的结构是为了促进跨学科合作，遵循四个主题目标：1)提供 为IDD相关研究提供最先进的基础设施；2)通过支持技术支持鼓励创新 开发并为新项目提供财政奖励；3)促进跨学科融合，方法是 鼓励教师之间和核心之间的跨学科研究；以及4)传播在以下方面的进展 向其他科学家传授技术，培训新的IDD调查人员，并向科学界和 利益攸关方参与社区外展工作。我们提出了5个交互核心：A：管理和 传播，监督核心职能和使用情况，确保质量和问责制，并促进 外展和传播；B：临床翻译、支持临床试验、招募、诊断和深度培训 表型鉴定和生物样本收集；C：遗传学、基因组学和生物信息学，执行 分析、测序、表达，并为计划和执行基因组数据分析提供资源； D：细胞、电路和系统，支持人类IPSC和三维有机体的发展，内外 活体电生理学和光遗传学；以及E：结构和功能可视化，提供培训， 体外显微镜、活体可视化微型照相机、动物和人类的访问和分析服务 结构和功能磁共振成像和光谱学。我们的模型研究项目专注于潜在的机制 两个IDDS患者的睡眠障碍，基于我们上一次提交的新发现：几乎没有慢波 在Dup15q综合征中睡觉。我们将研究Dup15q和Rett‘s睡眠障碍的潜在机制 使用多学科方法，包括临床部分、动物模型和大脑 使用患者来源的ipscs建立器官模型，以阐明睡眠生理改变的潜在机制 会导致认知功能障碍。该项目的结果将直接为制定干预措施的下一步提供信息 这可能会调节睡眠，进而调节IDDS的神经发育。

This proposal requests 5 years of additional funding for the UCLA Intellectual and Developmental Disabilities Research Center (IDDRC). For over 40 years, our mission has been to provide an optimal environment for conducting multidisciplinary research into the mechanisms underlying intellectual and developmental disabilities (IDDs), to translate these findings into effective treatments for IDDs, and disseminate these findings to the scientific community and the public. This submission expands on the translational focus that we began 5 years ago with an added emphasis on human research and clinical trials, and closer ties to the community. Each of the 5 cores are structured to facilitate interdisciplinary collaborations, following four thematic goals: 1) providing state of the art infrastructure for IDD related research; 2) encourage innovation by supporting technical development and providing financial incentives for new projects; 3) promote integration across disciplines, by encouraging interdisciplinary research among faculty and between cores; and 4) to disseminate advances in technology to other scientists, train new IDD investigators, and convey findings to the scientific community and stakeholders in community outreach efforts. We propose 5 interacting cores: A: Administration and Dissemination, which oversees core functions and usage, assures quality and accountability, and promotes outreach and dissemination; B: Clinical Translation, supporting clinical trials, recruitment, diagnosis and deep phenotyping, and biosample collection; C: Genetics, Genomics and BioInformatics, which performs genetic analysis, sequencing, expression, and provides resources for planning and executing analysis of genomics data; D: Cells, Circuits and Systems, supporting human iPSC and 3-dimensional organoid development, in- and ex- vivo electrophysiology and optogenetics; and E: Structural and Functional Visualization, which provides training, access, and analysis services for in vitro microscopy, mini-cameras for in vivo visualization, animal and human structural and functional MRI and spectroscopy. Our model research project focuses on mechanisms underlying sleep impairments in two IDDs, building on new findings from our last submission: a near absence of slow-wave sleep in Dup15q syndrome. We will examine mechanisms underlying sleep impairments in Dup15q and Rett's Syndrome using a multidisciplinary approach that includes a clinical component, animal models, and brain organoid model using patient-derived IPSCs, to elucidate how mechanisms underlying altered sleep physiology lead to cognitive dysfunction. Results from this project will directly inform next steps for developing interventions that may modulate sleep and, in turn, neurodevelopment in IDDs.