Ribosome function in plasticity and neurodevelopmental disorders

Learning involves long-term changes in the strength of specific synaptic connections between neurons. The translation of new proteins from existing mRNAs is required to sustain these changes. In fragile X syndrome (FX) and other single-gene disorders linked to autism and intellectual disability (ID), too much protein synthesis in neurons causes disruptions in synapses that may contribute to impaired learning. My goal is to understand how this occurs.

I will test whether abnormal production of ribosomes, which translate mRNA into protein, is causing neurological deficits in the Fmr1-/y mouse model of FX. I will also test whether changing ribosome production can alter the synaptic strengthening that occurs during learning. This will be done using advanced molecular strategies that can measure translation in specific neurons, combined with assays of synaptic function and behaviour. 

These studies may help to explain why too much protein synthesis causes neurological problems in FX and autism.