As described in the Overall component of this proposal, the overarching goal of the proposed Center is to understand and address the molecular and genetic mechanisms underlying the FMR1 premutation disorders, focusing on Fragile X tremor ataxia syndrome (FXTAS) and Fragile X associated primary ovarian insufficiency (FXPOI), and to answer fundamental questions regarding the roles of the CGG repeats in FMR1 function and dysfunction. The proposed Center integrates the substantial talents of research groups at Baylor College of Medicine (BCM), University of Michigan School of Medicine (UM) and Emory University School of Medicine (Emory). These groups have a significant history of collaborative interaction, and their common interests will lead to robust findings that will suggest therapeutic approaches to FXTAS, FXPOI and possibly fragile X syndrome (FXS). A well-defined leadership and management plan overseeing all research endeavors is critical for the success of the proposed work and will ensure that goals set by the Center Investigators are met in a timely and efficient manner. To accomplish the goals of our Center, the Administrative Core will support the Center's Investigators. Led by co-Directors Drs. David Nelson and Peter Todd (leaders of Projects 2 and 1, respectively), and assisted by Ms. LaTonya Beavers, the Administrative Core will be responsible for the management and administration of the overall Center. The planning and coordination of the synergistic research activities will be integrated through this central hub. Efforts will be conducted by an Executive Team, including Drs. Emily Allen and Stephanie Sherman, Project 3 Co-PIs, with the guidance of an Executive Advisory Board, composed of four external committee members who will address all Center operations and help to ensure the timely completion of each proposed project. In addition, the Administrative Core will be responsible for fiscal and resource management, as well as maintaining open lines of communication between Center Investigators, Project Staff, NIH officials, and FX researchers. A significant emphasis will also be placed on communication and engagement with the broader community of scientists and clinicians in neuroscience, genetics, neurology, obstetrics and pediatrics, and with the public. Training and educational opportunities are provided through regularly scheduled journal clubs, research presentations, and an annual Fragile X-Associated Disorders (FXaDs) Symposium beginning in year 2. These activities will foster a deeper interest in FX research in the new generation of young scientists, as well as encourage and stimulate investigators at all levels who may not be in our field to pursue studies related to FXaDs. We envision that the BCM-Michigan-Emory Fragile Research X Center will be a nexus of exciting scientific research, training and preclinical endeavors focused on development of novel therapeutics for FXaDs.