Patrick Knight

Investigating the mechanisms of aggregation associated with neurodegenerative olyglutamine (polyQ) diseases.

PolyQ diseases are inherited neurodegenerative disorders, characterised by the accumulation of polyQ-containing protein aggregates in the brain. The protein ataxin-3 is associated with the neurodegenerative polyglutamine (polyQ) disease pinocerebellar ataxia type-3. The aim of this project is to develop in vitro protocols to examine the aggregation pathway of a range of ataxin proteins with differing polyQ lengths and characterise the oligomeric intermediates observed. Following this, potential small molecule inhibitors of aggregation will be tested and their precise effect on protein aggregation studied. State-of-the-art ion mobility spectrometry-mass spectrometry (IMS-MS) methods will be employed during this project, supported by other biophysical techniques.