Imaging tau Aggregates in Models of Neurodegenerative Disease

The aggregation of the protein tau into small soluble species and ultimately neurofibrillar tangles is a critical process in the development of neurodegenerative diseases such as Alzheimer's disease or Progressive Supranuclear Palsy. The aim of this project is to develop sensitive analytical methods to directly image tau aggregates in solution or cell lysate, and hence determine the number and size of the tau aggregates present in the sample. This will be done using surface immobilised antibodies to capture the aggregates and fluorophore-labelled antibodies to image them at super-resolution to determine their size and shape. By then studying different cellular disease models over time we will determine which tau aggregates form initially, and how these aggregates change over time. We will then explore how cell stress or reducing or increasing protein removal processes, such as autophagy or proteasomal degradation, alters the formation of tau aggregates. The quantitative data from these experiments should allow us to build a model for the aggregation of tau in neurons and revealing the key molecular steps that should be targeted to prevent the formation of aggregates.