Centre for Integrative Physiology

Dr Emily Osterweil

Our research follows the central hypothesis that de novo protein synthesis in neurons is a fundamental requirement for learning, and dysregulation of this process is a core contributor to autism and intellectual disability (ASD/ID).

Emily Osterweil

Chancellor's Fellow

  • Hugh Robson Building
  • room 108
  • 15 George Square

Contact details

Address

Street

Edinburgh EH8 9XD

Personal profile

Research experience and education

  • Chancellor’s Fellow, Centre for Integrative Physiology, University of Edinburgh, UK
  • Postdoctoral Associate/Research Scientist, Picower Institute for Learning and Memory, MIT, USA
  • PhD in Neuroscience, Yale University, USA
  • BA in Biology, Oberlin College, USA

Honors, awards, and fellowships

  • Earl Stadtman finalist, NIH, USA
  • Pioneer Award, FRAXA Foundation, USA
  • Postdoctoral Fellowship, FRAXA Foundation, MIT, USA
  • Postdoctoral Fellowship, National Fragile X Foundation, MIT, USA
  • Distinction for PhD, Yale University, USA
  • Predoctoral Fellowship, Ruth L. Kirschstein NRSA, NIH/NINDS, Yale University, USA

Research

Our research questions are being investigated in multiple neural circuits using biochemical, electrophysiological and systems-level approaches.

Current projects include:

  1. Determining the role of NMDA receptors in local protein synthesis
  2. Tracking cell type specific changes in translation during plasticity using cell type-specific Translating Ribosome Affinity Purification and RNA-seq
  3. Investigating the translation control pathways linked to different postsynaptic receptors
  4. Exploring the role of protein turnover in synaptic plasticity

 

We are studying these basic biological questions using animal models of fragile X syndrome, Tuberous Sclerosis, and other neurodevelopmental disorders. It is our belief that identifying the mechanisms that go awry in these models will simultaneously address fundamental questions of synaptic function, and provide a better understanding of autism and ID.

 

Research Support

Current

  • Wellcome Trust/Royal Society, Sir Henry Dale Fellowship, PI: Emily Osterweil. Title: Differential regulation of protein synthesis in synaptic plasticity. Amount: £1,234,063
  • MRC, New Investigator Research Grant, PI: Emily Osterweil. Title: Targeting ERK and mTOR for the treatment of fragile X syndrome. Amount: £567,732
  • Tuberous Sclerosis Association, Postdoctoral Fellowship, PI: Sophie Thomson (Supervisor: Emily Osterweil). Title: Targeting the mGluR5-FMRP signaling pathway for the treatment of TSC. Amount: £153,971
  • FRAXA Research Foundation, Postdoctoral Fellowship. PI: Steph Barnes (Supervisor: Emily Osterweil). Title: Enhancement of NMDA receptor signaling for the treatment of fragile X syndrome. Amount: $90,000

Previous

  • Wellcome Trust-University of Edinburgh ISSF, Grant. PI: Emily Osterweil. Title: Targeting translation control pathways to treat fragile X and related neurodevelopmental disorders. Amount: £35,000
  • Royal Society, Start-up Grant. PI: Emily Osterweil. Title: Differential synaptic mRNA translation through ERK and mTOR signalling pathways. Amount: £15,000

Team members

Postdoctoral Fellows

  • Sophie R. Thomson, PhD
  • Stephanie A. Barnes, PhD
  • Sang S. Seo, PhD
  • Susana R. Louros, PhD

 PhD Students

  • Melania Muscas
  • Robert Hillary
  • Foteini Tsouki

Project Students

  • Caomihe Kirby, Masters student
  • Teresa Spano, Honours student

Collaborations

  • Prof. Peter Kind
  • Prof. David Wyllie
  • Dr. Emma Wood
  • Prof. Giles Hardingham
  • Dr. Nathalie Rochefort
  • Prof. Mike Cousin
  • Prof. David Fitzpatrick
  • Dr. Ian Simpson
  • Prof. Seth Grant
  • Dr. Noboru Komiyama
  • Prof. Mark Bear, MIT
  • Prof. Ka Wan Li, VU University
  • Prof. Mike Akins, Drexel University

Selected publications

2017              

  • Thomson, S. R.*, Seo, S. S.*, Barnes, S. A., Louros, S. R., Muscas, M., Dando, O., Kirby, C., Hardingham, G. E., Wyllie, D. J. A., Kind, P. C., Osterweil, E. K. Cell type-specific translation profiling reveals a novel strategy for treating fragile X syndrome. Neuron. In press. *, authors contributed equally 
  • Stoppel, L. J., Osterweil, E. K., Bear, M. F. The mGluR Theory of fragile X syndrome. Fragile X Syndrome: From Genetics to Targeted Treatment. Willemsen, R. & Kooy, F. (Eds.). Academic Press, 2017. ISBN: 0128045078, 9780128045077.

2016

  • Tao, J., Wu, H., Coronado, A., De Laittre, E., Osterweil, E. K., Zhang, Y., Bear, M. F. Negative allosteric modulation of mGluR5 partially corrects pathophysiology in a mouse model of Rett Syndrome. Journal of Neuroscience. 2016 Nov 23;36(47):11946-11958. 
  • Louros, S. R., Osterweil, E. K.  Perturbed proteostasis in autism spectrum disorders. Journal of Neurochemistry. 2016 Dec;139(6):1081-1092. doi: 10.1111/jnc.13723. Epub 2016 Aug 4.
  • Barnes, S. A., Thomson, S. R., Kind, P. C., Osterweil, E. K. FMRP and the pathophysiology of fragile X syndrome. Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability. Sala, C. & Verpelli, C. (Eds.). Academic Press, 2016. 8:113-128. ISBN: 9780128005330.

2015             

  • Barnes, S.A., Wijetunge, L.S., Jackson, A.D., Katsanevaki, D., Osterweil, E.K., Komiyama, N.H., Grant, S.G., Bear, M.F., Nägerl, U.V., Kind, P.C., Wyllie, D.J. Convergence of Hippocampal Pathophysiology in Syngap+/- and Fmr1-/y Mice. Journal of Neuroscience. 2015 Nov 11;35(45):15073-81. doi: 10.1523/JNEUROSCI.1087-15.2015.
  • Sidorov, M.S., Kaplan, E.S., Osterweil, E.K., Lindemann, L., Bear, M.F. Metabotropic glutamate receptor signaling is required for NMDA receptor-dependent ocular dominance plasticity and LTD in visual cortex. Proceedings of the National Academy of Sciences U. S. A. 2015 Oct 13;112(41):12852-7. doi: 10.1073/pnas.1512878112. 
  • Till, S.M., Asiminas, A., Jackson, A.D., Katsanevaki, D., Barnes, S.A., Osterweil, E.K., Bear, M.F., Chattarji, S., Wood, E.R., Wyllie, D.J., Kind, P.C. Conserved hippocampal cellular pathophysiology but distinct behavioural deficits in a new rat model of FXS. Human Molecular Genetics. 2015 Nov 1;24(21):5977-84. doi: 10.1093/hmg/ddv299. 

2014              

  • Sidorov, M. S., Krueger, D. D., Taylor, M., Gisin, E., Osterweil, E. K., Bear, M. F. Extinction of an instrumental response: A cognitive behavioral assay in Fmr1 knockout mice. Genes, Brain & Behavior. 2014 Jun;13(5):451-8. doi: 10.1111/gbb.12137.

2013      

  • Lohith, T. G., Osterweil, E. K., Fujita, M., Jenko, K. J., Bear, M. F., Innis, R. B. Is metabotropic glutamate receptor 5 upregulated in prefrontal cortex in fragile X syndrome? Molecular Autism. 2013 May 24;4(1):15. doi: 10.1186/2040-2392-4-15.
  • Osterweil, E. K., Chuang, S. C., Chubykin, A. A., Sidorov, M., Bianchi, R., Wong, R. K. S., Bear, M. F. Lovastatin corrects excess protein synthesis and prevents epileptogenesis in a mouse model of fragile X syndrome. Neuron. 2013 Jan 23;77(2):243-50. doi: 10.1016/j.neuron.2012.01.034. 

2012 and previous

  • Osterweil, E. K., Kind, P. C., Bear, M. F.  Lifting the mood on treating fragile X. Biological Psychiatry. 2012, 72(11):895-7. 
  • Auerbach, B. D., Osterweil, E. K., Bear, M. F.  Mutations causing syndromic autism define an axis of synaptic pathophysiology. Nature. 2011, 480(7375):63-8. 
  • Krueger, D. D., Osterweil, E. K., Chen, S. P., Tye, L. D., Bear, M. F.  Cognitive dysfunction and prefrontal synaptic abnormalities in a mouse model of fragile X syndrome.  Proceedings of the National Academy of Sciences. 2011, 108(6):2587-92. 
  • Osterweil, E. K., Krueger, D. D., Reinhold, K., Bear, M. F. Hypersensitivity to mGluR5 and ERK1/2 leads to excessive protein synthesis in the hippocampus of a mouse model of fragile X syndrome.  Journal of Neuroscience. 2010, 30(46):15616-27.
  • Krueger, D. D., Osterweil, E. K., Bear, M. F. Activation of mGluR5 Induces Rapid and Long-Lasting Protein Kinase D Phosphorylation in Hippocampal Neurons. Journal of Molecular Neuroscience. 2010, 42(1):1-8.
  • Bear, M. F., Dölen, G., Osterweil, E., Nagarajan, N. Fragile X: translation in action. Neuropsychopharmacology. 2008, 33(1):84-7. 
  • Dölen, G., Osterweil, E., Rao, B. S., Smith, G. B., Auerbach, B. D., Chattarji, S., Bear, M. F. Correction of fragile X syndrome in mice. Neuron. 2007, 56(6):955-62. 
  • Krendel, M., Osterweil, E. K., Mooseker, M. S. Myosin 1E interacts with synaptojanin-1 and dynamin and is involved in endocytosis. FEBS Letters. 2007, 581(4):644-50. 
  • Osterweil, E., Wells, D. G., Mooseker, M. S. A role for myosin VI in postsynaptic structure and glutamate receptor endocytosis.  Journal of Cell Biology. 2005, 168(2):329-38. 
  • Graesser, D., Solowiej, A., Bruckner, M., Osterweil, E., Juedes, A., Davis, S., Ruddle, N. H., Engelhardt, B., Madri, J. A. Altered vascular permeability and early onset of experimental autoimmune encephalomyelitis in PECAM-1-deficient mice. Journal of Clinical Investigation. 2002, 109(3):383-92.

Dr Osterweil's publications (pdf)

Patents

Bear, M. F. and Osterweil, E. K. (2012) Methods of treating seizure disorders. Publication WO2012054724 A1, US Patent application PCT/US2011/057099.