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