Using dynamic combinatorial selection methods to identify chemical modifications of protein function

Intrinsically disordered regions (IDRs), are ubiquitous stretches of protein that do not adopt a stable structure, are a major class of protein structure found in all living organisms, and, are predicted to be present in around a third of eukaryotic proteins. Crucially, IDRs are important and overrepresented in key signalling and disease pathways, spanning cancer to disorders of protein aggregation.
This PhD studentship will exploit chemical biology approaches to understand and manipulate the aggregation behaviour of a-synuclein - an intrinsically disordered protein which plays a key role in the neurodegenerative condition: Parkinson's disease. We will apply a state of the art combination of peptide and protein chemistry, fragment based ligand discovery methods and advanced biophysical techniques and structural methods to identify modifications to the sequence of a-synuclein and systematically map the consequences for its aggregation behaviour in vitro and in cells.
The results will establish a platform to identify modulators of IDRs/IDPs and open the door to new methods to delineate aggregation mechanisms a basic question of critical importance and tools to drive drug-discovery.