My PhD project aims to investigate soluble alpha-synuclein aggregates in the Parkinson's disease (PD) human brain. Dopaminergic neuron loss and insoluble protein aggregates called Lewy Bodies (LB's), predominantly composed of alpha-synuclein, are the characteristic pathological features of PD. Although LB's are typically regarded as the toxic species within the brain, the relationship between LB's and neuronal cell death is inconclusive. Many believe that small, soluble, intermediate protein aggregates (often called oligomers) are the true drivers of pathology in PD, although their small size and transient nature has made them difficult to study using classical microscopy. My PhD will utilize single-molecule and super-resolution microscopy to investigate the soluble aggregates from PD and neurologically normal human brain tissue, capturing the heterogeneity of aggregate structures that bulk measurement techniques fail to represent.
