A 4-year BBSRC DTP CASE PhD studentship is available to work with Professor Neil Oldham, in the School of Chemistry, University of Nottingham, and OMass Therapeutics. The studentship will focus on using innovative and cutting-edge mass spectrometry (MS) approaches to develop a novel screening platform for identifying new inhibitors of the smoothened receptor, an established anticancer target. The smoothened receptor is an integral transmembrane protein that forms a key component of the so-called hedgehog cell-cell signalling pathway. Mutations in the smoothened protein can lead to overactivation of the pathway, which results in cell proliferation and cancer, including medulloblastoma, basal-cell carcinoma and pancreatic cancer. Resistance to existing drugs makes the search for alternatives a high priority.
The project will exploit methodology developed within the Oldham group that utilises photochemical labelling of proteins to identify and map binding sites. By recording and quantifying changes in labelling patterns associated with the binding of another protein, or small molecule ligand, the techniques both detects a binding event and locates the binding site. MS is the ideal method for studying these effects due to its sensitivity and speed. The PhD student will take this approach in a new direction to develop a screening platform to show binding against the smoothened target. Once the methodology is developed and validated, it will be used to screen a large compound library to identify novel inhibitors of smoothened. Highly sought-after practical skills in expression, purification and handling of membrane proteins as well as cutting edge mass spectrometry will be gained from the project.
The studentship will also include a comprehensive training programme delivered by the DTP and School of Chemistry, which covers a wide range of specific and transferable skills. The University of Nottingham is a highly ranked Russell Group university with a history of excellence in teaching and research. OMass Therapeutics is an Oxford University spin-out backed by Syncona Ltd and Oxford Sciences Innovation that is harnessing high-resolution native mass spectrometry and other biophysical technologies to drive drug discovery in high definition for immunology and genetic disease.
Funding is available for four years from late September 2022. The award covers tuition fee (£4,567) at the home rate plus an annual stipend (£15,840) for 2022. This is set by the Research Councils. UK and international candidates are eligible to apply.