Emily Osterweil

 

Dr Emily Osterweil is a Chancellor’s Fellow in the Patrick Wild Centre and Centre for Integrative Physiology at the University of Edinburgh.

Understanding the genetic causes of autism spectrum disorder can only be achieved by finding out more about the production, or synthesis, of synaptic proteins.

EXPLORING DYSREGULATED SYNAPTIC PROTEIN SYNTHESIS
emily
Targeting protein synthesis to treat neurodevelopmental disorders. Fragile X syndrome (FXS) and tuberous sclerosis complex (TSC) are neurodevelopmental disorders with a high incidence of autism. Mouse models of FXS and TSC exhibit opposite alterations in cerebral protein synthesis, with FXS having too much protein synthesis and TSC having too little. Remarkably, mice bred to have both FXS and TSC mutations exhibit normal levels of mRNA translation, and this corrects several neurological phenotypes seen in both single mutants. This suggests that protein synthesis as a point of convergence for multiple genetic causes of autism. We are investigating several strategies for manipulating mRNA translation to correct pathological changes in FXS, TSC, and other neurodevelopmental disorders linked to autism.

Many neurodevelopmental disorders share a disruption in the way synapses — the points of contact between neurons — work. One of the key cellular processes underlying how synapses work is the synthesis or production of new proteins.

My research interest is in the local protein synthesis that supports synaptic changes when the growing brain is learning. My hypothesis is that this process is commonly dysregulated in multiple genetic causes of autism spectrum disorders.

My work has shown that abnormal mRNA translation is a shared pathophysiology of two of the most common monogenic causes of autism spectrum disorder, Fragile X Syndrome (FXS) and tuberous sclerosis complex (TSC). I have also shown that the exaggerated cerebral protein synthesis and epileptogenic phenotypes seen in a mouse model of fragile X syndrome (FXS) are due to hypersensitive signalling through a key pathway in the brain — called the ERK pathway.

Furthermore, my lab has shown that these can be corrected with the statin drug lovastatin. This treatment strategy has already shown promise in a recent clinical trial with fragile X syndrome patients.

As a relatively new member of the Patrick Wild Centre, my work will continue to investigate how dysregulated protein synthesis contributes to fragile X syndrome and related neurodevelopmental disorders.

In doing so, we will use new molecular techniques to identify which proteins are abnormally produced and test the contribution of these proteins electrophysiological and behavioural abnormalities in the fragile X syndrome mouse model. We believe that this strategy will reveal new information about the molecular changes that lead to fragile X syndrome, and identify new therapeutic targets.

Email: Emily.Osterweil@ed.ac.uk

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