Human late onset neurodegenerative diseases are characterized by the deposition within the CNS of toxic protein aggregates, present within both neurons and glial cells. Recent evidence has suggested that it is these misfolded proteins that propagate throughout the brain in a prion-like manner, inducing neural dysfunction, inflammation and eventual neurodegeneration.

In collaboration with the laboratories of Michel Goedert and Ben Falcon (MRC-LMB Cambridge, UK) we use a wide variety of novel mouse models of human disease to study the cellular basis of protein aggregation and their response to these aggregates. Of particular interest is the neuronal cytoplasmic aggregation of the nuclear RNA-binding protein TDP-43, the cytoplasmic aggregation of the microglial protein TREM2 within astrocytes and finally, the cytoplasmic aggregation of tau protein within neurons which is potentiated by the extracellular deposition of β-amyloid. 

We are currently determining the ultrastructural appearance of filamentous forms of these proteins and documenting their cellular localization. We aim to elucidate the mechanisms by which these proteins spread throughout the CNS.