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  3. Special Seminar with Emily Osterweil, PhD, "The long and short of altered translation in Fragile X Syndrome"
Special Seminar with Emily Osterweil, PhD, "The long and short of altered translation in Fragile X Syndrome"
The Picower Institute for Learning and Memory

Special Seminar with Emily Osterweil, PhD, "The long and short of altered translation in Fragile X Syndrome"

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Add to CalendarAmerica/New_YorkSpecial Seminar with Emily Osterweil, PhD, "The long and short of altered translation in Fragile X Syndrome"07/13/2022 12:00 pm07/13/2022 1:00 pm,
July 13, 2022
12:00 pm - 1:00 pm
Location
,
Contact
bgreeno@mit.edu
    Description

    This seminar will be held virtually. Please click here to join or enter https://mit.zoom.us/j/96694319234 into your search bar.

    ______________________________________________________________

    Special Seminar with Emily Osterweil, PhD, University of Edinburgh

    Talk Title: The long and short of altered translation in Fragile X Syndrome

    Abstract: Dysregulated protein synthesis is a core pathogenic mechanism in Fragile X Syndrome (FX). The mGluR Theory of FX predicts that pathological synaptic changes arise from the excessive translation of mRNAs downstream of mGlu1/5 activation. Here, we use a combination of CA1 pyramidal neuron-specific TRAP-seq and proteomics to identify the overtranslating mRNAs supporting exaggerated mGlu1/5 -induced long-term synaptic depression (mGluR-LTD) in the FX mouse model (Fmr1-/y). Our results identify a significant increase in the translation of ribosomal proteins (RPs) upon mGlu1/5 stimulation that coincides with a reduced translation of long mRNAs encoding synaptic proteins. These changes are mimicked and occluded in Fmr1-/y neurons. Inhibiting RP translation significantly impairs mGluR-LTD and prevents the length-dependent shift in the translating population. Together, these resu­lts suggest that pathological changes in FX result from a length-dependent alteration in the translating population that is supported by excessive RP translation.

    Bio: Emily Osterweil is a Professor of Molecular Neuroscience and a Wellcome Trust Senior Research Fellow at the University of Edinburgh. She received her PhD in Neuroscience from Yale University, after which she performed postdoctoral research in the lab of Mark Bear at the Picower Institute at MIT. Her goal is to understand how mRNA translation in neurons contributes to brain function, and to identify how disruptions in this process lead to pathological changes in neurodevelopmental disorders.

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