Molecular and cellular mechanisms of protein aggregation and toxicity in models of neurodegeneration

Protein quality-control systems normally prevent the accumulation of toxic, misfolded species that cause degenerative diseases. Through genetic and biochemical changes of unclear origin, protein quality control becomes less effective with ageing, eventually resulting in late-onset neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. A better understanding of the mechanisms of protein disaggregation would enable new approaches to understanding toxic gain of function, how cells handle aggregates, and the failure of protein quality control in ageing individuals. Professor Saibil plans to investigate the cellular machinery for processing amyloid and related aggregates of misfolded proteins using a combination of molecular and cellular electron microscopy with mechanistic studies.