Explaining the elusive first step in neurodegenerative diseases by solving the structures of disordered proteins in physiological environments

Project Code

MRCNMH26Ex Phillips

Project Type

Wet lab

Research Theme

Neuroscience and Mental Health

Project Summary Download

Summary

Neurodegenerative diseases, such as Parkinson’s disease, are strongly linked to the aggregation of intrinsically disordered proteins (IDPs). However, the precise triggers and mechanisms driving this process remain unclear without molecular structural detail. Determination of 3d protein structure has advanced recently (2024 Nobel Prize for AlphaFold) but only explains folded proteins. IDPs are a major frontier because they are exquisitely sensitive to environmental conditions, dramatically changing their molecular structure in response to stimuli and cellular trafficking. Here, we will determine IDP structures in their native physiological environments to explain their influence on the formation of toxic aggregates and neuronal cell death.

Lead Supervisor

Dr Jonathan Phillips

Lead Supervisor Email

jj.phillips@exeter.ac.uk

University Affiliation

Exeter