I am working on a project that brings together two cutting-edge transgenic mouse models developed in the Wade-Martins Laboratory. The Laboratory has generated a transgenic mouse line overexpressing human wild-type alpha-synuclein within a bacterial artificial chromosome (BAC). This model has been shown to recapitulate the sequence of pathological events seen in Parkinson's (Janezic, S et al. 2013). From a young age, these mice exhibit a reduced release of dopamine in the dorsal striatum, while old animals display an age-dependent loss of nigrostriatal dopaminergic neurons and motor impairments characteristic of Parkinson's.
In order to account for the deficiencies observed in these mice, I will carry out a comparative study of the translated mRNAs in dopaminergic neurons. This will be achieved by making use of a second transgenic mouse line that enables the profiling of translated mRNAs specifically in dopaminergic neurons (bacTRAP mice). By crossing both mouse lines, I will be able to analyse perturbations in translated gene expression in vulnerable and resistant dopaminergic neurons. By investigating translational changes occurring during Parkinson's disease in vivo, we hope to obtain a more complete understanding of the underlying pathological pathways.