PhD Studentship: Characterisation of Live Cell Drug Binding Using a Novel NMR Technique to Accelerate Drug Development

Primary Supervisor – Dr Leanne Stokes

Pharmacologists typically assess affinity/efficacy of drugs through indirect binding assays or functional assays. Our team has developed a novel NMR method for investigating drug-receptor interactions on live cells and this project will expand the use of the NMR tool to study several membrane-embedded receptors. This will include P2X ligand-gated ion channels, G-protein coupled receptors and receptor tyrosine kinases which are important therapeutic targets for chronic pain, cancer, and psychiatric disorders. The saturation transfer difference (STD) NMR method allows drug contacts to be mapped at the atomic level and from this we can design new synthetic drug molecules (analogues). The project will use NMR data to inform structure-activity relationships for a variety of allosteric modulators and to enable the identification of drug binding sites on these receptors. We will synthesize a range of chemical analogues to develop the pharmacological profile for these important receptors and screen the analogues on cells expressing the receptors. To investigate drug binding sites, we will mutate key amino acids in the predicted binding pocket and determine if the drug-receptor contact profile changes. The student will gain skills in drug design, computational docking, STD NMR, chemical synthesis, cell culture, receptor expression in mammalian cells, site-directed mutagenesis, and pharmacological assays.  

This project would suit a graduate in Pharmacology, Biomedicine, Pharmacy, Pharmaceutical Science or Chemistry with curiosity and passion to learn. We will provide additional training in transferable skills, critical thinking, problem solving, science communication and opportunities to attend national and international conferences to present work.  

The School of Chemistry, Pharmacy and Pharmacology at UEA has a growing postgraduate community with many opportunities for involvement in scientific events and outreach. We welcome applications from all backgrounds in line with our commitment to equality, diversity, and inclusivity.  

Funding Details

Additional Funding Information

This PhD project is in a competition for a Faculty of Science funded studentship. Funding is available to UK applicants and comprises ‘home’ tuition fees and an annual stipend of £19,237 (for a maximum 3 years)

Closing Date: 27 November 2024 (at 11.59 pm) 

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