Studying the mechanism of PROTACs in drug discovery by high-throughput MALDI TOF mass spectrometry

Applications are invited for a fully funded 4-year BBSRC iCASE PhD studentship to work in the group of Prof Matthias Trost at Newcastle University on a collaborative project with GSK.

The ubiquitin system is becoming an exciting new area for drug discovery. Particularly, targeted protein degradation using bifunctional small molecules known as Proteolysis-Targeting Chimeras (PROTACs) is emerging as a novel therapeutic modality (Bondeson et al. Nature Chem Biol, 2015). PROTACs redirect the cellular protein quality control machinery to target specific proteins for highly selective degradation and removal from the cell. However, the mechanisms of this process are poorly understood.

In this highly collaborative PhD between GSK and the Trost lab you will be trained in biochemistry and state-of-the-art techniques such as high-throughput MALDI TOF mass spectrometry. We have used this technology successfully in the ubiquitin system (Ritorto et al, Nature Comm, 2014; De Cesare et al, Cell Chem Biol, 2018) and other areas. This project includes an industrial placement at GSK.

The Institute for Cell and Molecular Biosciences (ICaMB) at Newcastle University is funded and equipped to the highest international standards. Our new mass spectrometry facility is equipped with state-of-the art-mass spectrometers including an Orbitrap Fusion Lumos and a Bruker RapiFlex MALDI TOF-TOF.