Center for Collaborative Research in Fragile X Syndrome
The Center brings together three established investigators: Dr. Eric Klann (New York Univeristy), Dr. Gary Bassell (Emory University, Atlanta), and Dr. Joel Richter (University of Massachussetts Medical School), who each study translational control and its regulation in the mammalian brain.
The central focus of our collaboration is to assess how re-balancing translational homeostatis in the diseased (FMRP lacking) brain ameliorates and indeed reverses the pathophysiology of FXS.
By either inhibiting or ablating key signaling molecules that lead to translation (P13 kinease, Bassell; p7056 kinase 1 [S6K1]), Klann, or by ablating a translational control protein (CPEB, Richter in collaboration with Bassell and Klan), these investigators have rescued critical biochemical, morphological, physiological and behavioral phenotypes in Fmr1 null mice.
The purpose of the Center is to understand how modulation of the translational apparatus and upstream signaling pathways in the brain rescues FXS pathophysiology in mice. The major goals are four-fold: 1) to use multiple genetic and pharmacologic murine models to determine the identities of mRNA molecules whose translation is rescued (i.e., restored to wild type levels) by alteration of the translational landscape; 2) to determine the importance of specific mRNAs for FXS whose translation is rescued; 3) to investigate the molecular mechanism by which translation is rescued; 4) to analyze human cell for rescue of translation and importance for FXS.