Responsible for biochemical and biophysical assay development for small molecule drug discovery projects.

The application of the fragment-based approach to drug discovery to the development of protein–protein interaction modulators. My work within this project directly involves all aspects of the FBDD screening cascade: protein purification, fragment screening, assay development (fluorescence polarisation, ligand-based proton NMR, fluorescence-based thermal shift), biophysical characterisation, chemical synthesis and X-ray crystallography.

PhD thesis title: Targeting Protein–Protein Interactions with Fragment-Based ApproachesSupervised by Professor Chris Abell, with funding from Cancer Research UK (Medicinal Chemistry Training Programme). Key skills: ▸ DNA cloning and mutagenesis ▸ Protein expression and purification ▸ Fragment-based drug discovery methodology ▸ Fluorescence-based thermal shift ▸ Fluorescence polarisation assay ▸ Isothermal titration calorimetry ▸ Ligand-based proton NMR ▸ Circular dichroism ▸ Peptide synthesis ▸ Chemical synthesis ▸ X-ray crystallography (crystallisation, data collection, refinement)

Rotation 1 (3 months)Under the supervision of Professor Ian Paterson and Dr Jonathan Goodman, this project involved work towards the synthesis of a hybrid macrolide comprising of fragments of dictyostatin and discodermolide in conjunction with computational modelling to elucidate potential binding modes on beta-tubulin.Rotation 2 (3 months)Under the supervision of Dr Sophie Jackson, this rotation involved preliminary work towards setting up an AlphaScreen®-based assay for the identification of protein-protein interaction inhibitors of the chaperone Hsp90 and its co-chaperones.Rotation 3 (3 months)Under the supervision of Dr Fanni Gergley, this rotation was an exploration into the role of certain proteins essential for correct mitotic spindle assembly in relation to the kinesin HSET/KiFC1 a protein that has been shown the be necessary for cells to manage supernumerate centrosomes.

Under the supervision of Professor Christopher Schofield, this project involved the application of a proteolysis/mass spectrometry method for investigating the effects of inhibitors the structure of the prolyl hydroxylase, PHD2.