Two PDRA positions (36 months from October 23) at the University of Liverpool

We have a Chemistry PDRA and a Biophysics-structural biology PDRA positions to 
develop non-covalent binders to SOD1 suitable as PROTAC degraders for the 
treatment of motor neuron disease association. The Chemistry PDRA position 
would be based in Chemistry department (Professor O’Neill/Dr Nixon), The second 
PDRA would be based in the Biosciences complex (Professor Samar Hasnain/Dr 
Antonyuk/Dr. Awais). The project will benefit from collaboration with leading 
PROTAC expert at Dundee (Ciulli) and team at the Alzheimer's Research UK UCL 
Drug Discovery Institute (ARUK UCL DDI) led by Fiona Ducotterd. We aim to 
provide novel scaffolds that bind to the as-yet unexploited validated pocket 
surrounding Trp32. We will investigate for the first time, a fragment-based 
approach to drug design targeted against destabilised SOD-1. Direct 
crystallographic visualisation will be used to undertake lead optimisation and 
designing of CNS penetrant versions of initial small molecules hits. This 
non-covalent binding is suitable for a PROTAC approach. In-cell visualisation 
of aggregation and cell death would be undertaken using confocal microscopy. 
Applicants with relevant experience are encouraged to make informal enquiries 
via email to s.s.hasn...@liverpool.ac.uk<mailto:s.s.hasn...@liverpool.ac.uk>, 
pmone...@liverpool.ac.uk<mailto:pmone...@liverpool.ac.uk> and 
s.anton...@liverpool.ac.uk<mailto:s.anton...@liverpool.ac.uk>

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