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.