Neuroscientists and physicians continue to struggle to understand the pathophysiological mechanisms that underlie mental illness, and even more so to translate this information into the personalized therapies needed for diseases. Although research over the past five decades has uncovered genes, gene variants, molecular networks, cellular interactions and brain pathways supporting brain disorders, our translation of this information remains limited. A new generation of neuroscientists is needed that understand, and can exploit, 1) the functional impact of genetic and epigenetic variation in vivo, 2) the developmental and regulatory context within which genes produce alterations in synaptic physiology, 3) the circuit-level pathologies that lead to changes in behavior and 4) the best practices in translating research findings into novel therapies. We propose The Vanderbilt Postdoctoral Training Program in Functional Neurogenomics as a vehicle to insure a merger of disciplines, where trainees gain experience in the opportunities afforded by genetic model systems, gain expertise in the translation of human genetic findings into construct-valid animal models, learn to manipulate molecules, cells and circuits with advanced approaches in vivo, and gain experience in capturing the physiological and behavioral consequences of such manipulations. We build our program on a significant investment over the past two decades by Vanderbilt in neuroscience faculty, educational programs, technological expertise and core facilities. Our Program Director is Randy D. Blakely, Ph.D., an NIMH MERIT awardee and Director of the Vanderbilt Silvio O. Conte Center for Neuroscience Research. Dr. Blakely's research ranges from forward and reverse genetic studies in C. elegans to the modeling of mental illness-associated gene variation in transgenic mice, to the identification of functional human genetic variation underlying autism and ADHD. Two established neuroscientists with a long-standing interest in advancing the careers of junior scientists oversee the Program. The Program Co-Director is Roger D. Cone, Ph.D., Chair of the Department of Molecular Physiology &Biophysics at Vanderbilt, and an elected member of the National Academy of Sciences. Dr. Cone's research incorporates the tools of modern genetics, molecular biology, biochemistry and behavior, with a focus on CNS control of appetite and eating disorders. Similar to Dr. Blakely, the paradigms used in Dr. Cone's research ranges across powerful genetic model systems, including transgenic zebrafish and mice, to research probing for functional gene variation underlying eating disorders. Like Dr. Blakely, Dr. Cone has trained dozens of predoctoral and postdoctoral fellows, bringing significant mentorship experience to the Program.
Neurobehavioral disorders, such as autism, anorexia nervosa, obsessive-compulsive disorder, schizophrenia, bipolar disorder, eating disorders and depression, reduce the quality of life and productivity for tens of millions of Americans each year. Exciting new research has revealed multiple genetic and environmental determinants of risk for these disorders, though how and when these changes impact brain function and behavior, and how we can capitalize on these discoveries for new treatments, is largely unknown. Through the Vanderbilt Postdoctoral Training Program in Functional Neurogenomics, we seek to train our fellows in the concepts and techniques needed 1) to identify novel genes acting in pathways that produce risk for brain disorders, 2) to manipulate genes, gene expression and molecular pathways in animals to produce realistic models of mental illness, and 3) to manipulate brain structure and function in vivo as a critical step toward the development of novel medications.
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|Abe, Masahito; Seto, Mabel; Gogliotti, Rocco G et al. (2017) Discovery of VU6005649, a CNS Penetrant mGlu7/8 Receptor PAM Derived from a Series of Pyrazolo[1,5-a]pyrimidines. ACS Med Chem Lett 8:1110-1115|
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