Professor Sheena Radford - University of Leeds

Event details

Abstract

Proteins are amazing three-dimensional machines that carry out life’s essential processes. Modern methods in the biological sciences are enabling us to see these structures at work in ever-increasing molecular detail. Yet the most fundamental process of all, how proteins fold and assemble into complex machines, remains mysterious. Errors of protein folding can give rise to devastating diseases that are a major threat to the health of society, such as Alzheimer’s and Parkinson’s diseases. Given the enormous burden of these, and other, disorders associated with protein misfolding, understanding how proteins fold and why misfolding results in disease has never been more important.

In this seminar I will survey our current knowledge of protein folding; discuss how Alphafold and other computational methods are revolutionising our understanding of protein structure and behaviour; and share some of our newest discoveries in our quest to elucidate how proteins misfold to form beautiful, but deadly, amyloid fibrils associated with disease. I will describe our exploits to determine how sequence variations influence the delicate balance between correct folding and aggregation and how cellular conditions can refine or switch assembly to deliver new aggregate forms. Using deep mutational scanning and machine learning I will talk about how we are learning to interpret the hidden codes in protein sequences that dictate protein fate.