Using a combination of biophysical and cell biology studies we are investigating how the polyglutamine expansions found in Huntington's patients mediate their toxicity at a molecular level.
Due to an ageing population chronic neurodegenerative disorders (Alzheimer's, Parkinson's and Huntington's Disease, HD) will be the major burden on modern society. Similar to ageing, these diseases are characterised by intra/extracellular protein misfolding resulting in the formation of amyloid deposits, ordered fibrillar aggregates that typify these diseases. Although the final structures of these amyloid deposits are being elucidated, our molecular understanding of what causes the formation of these deposits and the role by which they mediate neurotoxicity remains poorly understood. To address this problem we will employ a multidisciplinary approach to study the aggregation processes of an aggregation-prone model protein (polyglutamine expanded huntingtin (htt)), a protein linked to HD. The research seeks to understand the structural transitions involved in fibril formation and correlate these with aging processes such as free radical production and lipid peroxidation in an attempt to understand the pathology observed at a molecular level.
Funding: BBSRC-DTA studentship to Mr Chris Ford (November 2010-2015)