Determining the molecular basis of fragile X disorders

Neurodevelopmental and fertility disorders represent significant health burdens in Canada, as approximately 1 in 66 Canadian youth are diagnosed with an autism spectrum disorder, and 1 in 6 Canadian couples experience infertility. Neurons and reproductive cells (oocytes and sperm) rely extensively on a form of control of gene expression called translational control. Mutations in the translational regulatory gene Fmr1 underlie the fragile X disorders known as fragile X syndrome (FXS) and fragile X primary ovarian insufficiency (FXPOI), which are leading causes of autism and premature ovarian failure respectively.

The proposed research will build upon my recent discoveries of Fmr1’s role in promoting the translation of genes encoding large proteins — many of which are associated with autism — in order to understand the mechanism by which Fmr1 activates translation. Knowledge of this mechanism will be of immense clinical value, enabling the development of novel therapies for citizens of British Columbia experiencing a fragile X disorder or related autism spectrum or infertility disorder.