Dr Emily Osterweil

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 Theme

• Synapses, Circuits and Behaviour 

Research

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

Current projects include:

• Determining the role of NMDA receptors in local protein synthesis

• Tracking cell type specific changes in translation during plasticity using cell type-specific Translating Ribosome Affinity Purification and RNA-seq

• Investigating the translation control pathways linked to different postsynaptic receptors

• Exploring the role of protein turnover in synaptic plasticity

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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.

Funding

• 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

Team members

Postdoctoral Fellows

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

 PhD Students

• Melania Muscas

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.

Information for students:

Willingness to discuss research projects with undergraduate and postgraduate students: YES - please click here