The Mason research group focuses on the screening, design, synthesis, and characterisation of peptide-based antagonists that inhibit disease-relevant targets with high affinity and specificity. Our central aim is to disrupt protein–protein interactions (PPIs) that are essential for target function and that are often inaccessible to conventional small-molecule therapeutics.

While the biophysical forces that govern protein stability are now relatively well understood, the determinants of interaction specificity remain much less clear. To address this challenge, we develop and apply intracellular peptide library screening approaches that operate within the native complexity of the living cell. Key platforms include the Protein Fragment Complementation Assay (PCA) and Transcription Block Survival (TBS), both of which employ semi-rational library design to select peptide antagonists that engage defined protein targets and ablate their biological function in situ.

To further enhance selectivity, we have developed the Competitive and Negative Design Initiative (CANDI), which increases target specificity during screening by co-expressing potential off-targets or first-generation hit sequences during selection. This strategy enables direct discrimination between closely related interaction partners and supports the discovery of highly selective inhibitors.

Peptides identified through these screening platforms are subjected to detailed biochemical, biophysical, and cellular characterisation. Insights gained from these studies have enabled us to develop computational (InsiliCoil) and experimental tools for predicting PPI stability and specificity directly from primary sequence, and to design inhibitory peptides and in silico peptide libraries with improved performance.

Our approaches have been applied to a broad range of therapeutically relevant systems, including signalling proteins, transcription factors, and amyloidogenic proteins such as β-amyloid and α-synuclein, which are implicated in the pathogenesis of Alzheimer’s and Parkinson’s diseases. A particular focus of the group is the development of strategies to target classically “undruggable” transcription factors using conformationally constrained, intracellularly active peptides.

The group employs a multidisciplinary toolkit spanning molecular biology, chemical biology, and molecular biophysics, with a strong emphasis on intracellular screening, intracellular peptide constraint chemistry, and mechanism-driven validation. Our research has been supported by the BBSRC, MRC, EPSRC, CRUK, Wellcome Trust, Royal Society, Alzheimer’s Society, Parkinson’s UK, and Alzheimer’s Research UK, and underpins translational activity through close links with academic and industrial partners.

In addition to his academic role, Professor Mason is Chief Scientific Officer of Revolver Therapeutics, a University of Bath spin-out company developing peptide-based inhibitors of transcription factors for oncology indications. Revolver Therapeutics has received Innovate UK funding and is supported by venture capital investment. Professor Mason also serves as a scientific consultant and advisor to Sapience Therapeutics, a US-based biotechnology company advancing peptide therapeutics targeting transcription factor–driven cancers.

I would be pleased to hear from potential applicants interested in joining my research group. We have a range of ongoing projects focused on the design, synthesis, and biophysical and cellular characterisation of peptide-based inhibitors targeting proteins involved in human disease.

I welcome enquiries from students wishing to undertake a PhD, as well as from postdoctoral researchers seeking support for external or personal fellowship applications, including BBSRC fellowships, Royal Society schemes (e.g. Newton International Fellowships), EMBO, HFSP, Marie Skłodowska-Curie Actions, and other government-funded programmes.

Please contact Jody Mason for an informal discussion.