EPSRC CASE PhD studentship: Novel high-throughput approaches for the rapid analysis of target engagement by mass spectrometry (collaboration with Medicines Discovery Catapult)

The ability to provide fast and efficient readouts for drug engagement with targets (proteins and oligonucleotides) is a key driving technology in the biopharma pipeline, e.g. in high-throughput screening. Optical readouts are common but provide a somewhat binary answer, whereas the application of mass spectrometry (MS) to target heterogeneity, stoichiometry of binding and also structural effects (using ion mobility) has so far been hampered by the lack of robustness and the low-throughput of currently used sample inlet methods – mainly electrospray-ionization.
This was recognized when a novel acoustic liquid-handling approach (“Echo”) with a capability of injecting 10,000 samples/hour was first adapted to MS analysis. This technology, now hosted at the Medicines Discovery Catapult (MDC, Alderley Edge), enables high-throughput assays for ligand screening (direct binding detection). We propose novel in-line chromatography based separation and purification, as well as further developing droplet-based inlet systems in collaboration with colleagues at Leeds’ Engineering department. This will enable more robust readouts, e.g. from cellular extracts, without need for complex sample preparation, as well as structural/conformational readouts (using ion mobility) and top-down sequencing (ETD/SID).
You will work under the supervision of Prof Frank Sobott and Dr James Ault, in collaboration with Dr Martin Bachman (Medicines Discovery Catapult, Alderley Edge) in Leeds’ world class Biomolecular Mass Spectrometry laboratory which houses 7 instruments dedicated to structural mass spectrometry. You will receive training in structural mass spectrometry methodologies as well as having the chance to further develop a cutting-edge sample inlet system with great interest in the bio/pharma industry, and push the limits of current structural mass spectrometry capabilities.