Professor Sheena Radford OBE, FMedSci, FRS

Talk: From fold to failures: How sequences shape protein fate

Protein sequences encode not only structure, but also the propensity to misfold and aggregate. Subtle changes in amino acid sequence can dramatically alter folding and assembly pathways, leading to functional proteins or pathological amyloid fibrils. In this talk 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. I will discuss how we are using methods such as deep mutational scanning and machine learning to teach us how to interpret the hidden codes in protein sequences that dictate protein fate. Understanding these relationships could provide critical insight into disease mechanisms and opens avenues for engineering sequences with controlled folding behaviour.

About this speaker

Sheena Radford completed her BSc in Biochemistry at the University of Birmingham and PhD at the University of Cambridge. After postdoctoral fellowships at the University of Oxford she moved to Leeds in 1995 to establish her independent research group. She was a founding member of the Astbury Centre for Structural Molecular Biology and its Director from 2012-2021. Sheena currently holds a Royal Society Research Professorship and is Astbury Professor of Biophysics. Her research focuses on mechanisms of protein folding and misfolding in amyloid diseases, and how bacteria fold proteins into their outer membrane, of importance in antimicrobial resistance. Along with her group members and collaborators, many in the Astbury Centre, she has published >360 papers and has served on many panels, grant bodies and advisory boards. She is a Fellow of the Royal Society, the Academy of Medical Sciences, the Royal Society of Chemistry, the Royal Society of Biology, EMBO and Academia Europaea. She received an OBE in the Queen’s honours list in 2020 for her services to molecular biology and was recently elected an International Member of the USA National Academy of Sciences.