Jody Mason
Professor
University of Bath
Talk Information
Peptides in Oncology
18 June 2025, 11:25am - 11:50am, in the Pacific Jewel Ballroom
L43 – Switching off Transcription Factors Using Intracellular Library-derived Peptides
Academic Background
Professor Jody Mason received his B.Sc., Hons., in Biochemistry and his Ph.D. from the University of Bristol, UK, where he studied the folding and stability of disulfide-bridged proteins. Following postdoctoral research in the fields of protein misfolding, Manchester, UK, and peptide–DNA interactions, Freiburg, Germany, he established his independent research group at the University of Essex in 2007. In 2015 he moved his research group to the University of Bath. His academic trajectory has focused on the development of peptide-based tools and therapeutics to target challenging protein–protein interactions.
Research Focus
Professor Mason’s laboratory specialises in targeting transcription factors and other classically “undruggable” protein–protein interactions using intracellularly screened peptide libraries. He has developed two key platforms – the Protein Fragment Complementation Assay, PCA, and Transcription Block Survival, TBS, to enable selection of potent and selective peptide inhibitors within living cells. His group is also advancing approaches for peptide cyclisation, covalent target engagement, and the rational design of conformationally constrained peptide antagonists. These strategies have been applied to oncogenic transcription factors and misfolded proteins relevant to neurodegenerative disease.
Notable Contributions
Professor Mason has made substantial contributions to the discovery and optimisation of intracellular peptide therapeutics, particularly in systems where transcription factor dysregulation or protein aggregation is central to pathology. His group recently demonstrated that library-derived constrained peptides can be selected in live cells based on their ability to block target DNA binding. Recent publications in Advanced Science, ACS Chemical Biology, Molecular Neurodegeneration, Molecular Cancer, Cell Reports Physical Science, and JACS Au highlight the discovery of peptide antagonists with selective activity against disease-associated transcription factors and the use of chemical and enzymatic strategies to cyclise peptides inside cells.
Professional Engagements
Professor Mason served on the Alzheimer’s Research UK Grant Review Board, 2016–2023, and is a long-standing member of BBSRC Panel D, since 2017. He is currently funded by EPSRC, BBSRC, Innovate UK, and Alzheimer’s Research UK Project Grants, and co-leads the Bath Advanced Research and Drug Discovery, BARDD, Centre, an interdisciplinary initiative supporting translational drug discovery. In addition to his academic role, he serves as Chief Scientific Officer of Revolver Therapeutics, a University of Bath spinout focused on peptide-based transcription factor inhibitors, and is an advisor to Sapience Therapeutics, a US-based biotechnology company developing peptide therapeutics in oncology.
Protein-protein interactions, and in particular Transcription Factors, TFs, remain compelling drug targets, yet are often intractable to small molecules and inaccessible to larger biologics. Peptides occupy an attractive middle ground if they can become suitable ordered for target engagement. We utilise intracellular peptide library screening approaches to identify selective peptide-based inhibitors that can functionally antagonise TFs.
There are two novelties to our approach:
i| our Transcription Block Survival, TBS, peptide-library screening platform in which TF consensus sites are placed directly into the coding region of an essential gene. Subsequent TF binding within the gene directly blocks gene transcription leading to cell death under selective conditions. Cell survival is therefore only possible if antagonists bind to the TF, but more importantly can prevent it from binding to its consensus sequence, thus shutting down TF function. TBS is an entirely tag-free genotype-to-phenotype approach, selecting desirable attributes such as high solubility, target specificity, biostability and low toxicity within the complex environment of the cell. TBS facilitates rapid library screening to accelerate identification of therapeutically valuable sequences.
ii| concomitant deployment of cell penetrating crosslinkers. These enter cells to post-translationally constrain every library member into conformations not possible via genetic encoding alone, to select only those in which crosslinking translates into improve target antagonism. Screening ultra-structured biostable peptide libraries, where entire libraries are constrained during the search is highly desirable as it prevents a slow and costly retrospective trial-and-error search for beneficial crosslinkers, positions, and sequences.
Using several different exemplars, I will discuss how library-derived constrained peptide antagonists are derived and discuss their characterisation using a range of biophysical and cancer cell-based assays.