Andy Brennan's path through peptide science reads like a tour of the UK's leading protein chemistry groups, each stop adding new tools to his repertoire. His introduction to peptides began during his undergraduate studies at the University of Bristol in the laboratory of Dek Woolfson, where he explored coiled-coil helical assemblies, an experience that shaped his master’s research and sparked a lasting interest in peptide structure and function. Doctoral research at the University of Nottingham with Mark Searle shifted his focus to the biophysical characterization of protein-protein interactions, grounding him in the quantitative methods that would later prove essential for drug discovery.
Aerial view of the campus at the University of Bath.
A postdoctoral position at the University of Bath with Jody Mason proved pivotal. Together they developed the Transcription Block Survival assay, a screening platform that tests genetically encoded peptide libraries directly inside cells. Unlike conventional approaches that merely select for target binding, TBS identifies peptides that functionally inhibit transcription factors by preventing them from engaging DNA. The platform addresses a fundamental challenge in peptide therapeutics: many candidates that bind targets effectively in vitro lack selectivity and stability, or prove toxic in biological contexts. TBS sidesteps these issues by selecting hits that already work in a cellular environment.
This technology became the foundation for Revolver Therapeutics, a University of Bath spin-out that Brennan co-founded in 2023. The company is developing constrained peptide inhibitors against transcription factors, proteins long considered "undruggable" by conventional small molecule approaches. Revolver has attracted investment from the UK Innovation Science and Seed Fund and o2h Ventures, and recently partnered with The Institute of Cancer Research to evaluate inhibitors against childhood gliomas, aggressive brain tumors with few treatment options.
The science continues to advance. A 2025 publication in Advanced Science described covalent peptide inhibitors of cJun, an oncogenic transcription factor. By screening a library containing cysteine options at multiple positions, Brennan and colleagues identified a residue positioned for disulfide bond formation with cJun's DNA-binding domain. Converting this to an electrophilic warhead produced irreversible inhibitors capable of penetrating human melanoma cells and depleting oncogenic cJun levels. As Brennan described it, the inhibitor "works like a harpoon that fires across to its target and will not let go."
In further work, Andy has modified the underlying genetic engineering of the TBS system to improve efficacy, with an 11.3-million-member library screen identifying a potent ATF2 antagonist within three months. The most recent development is the ability to screen chemically constrained peptides within the live bacterial system, which identified a CREB1 inhibitor with selective potency in melanoma and colorectal cancer cells.
Now a Lecturer in Medicinal Chemistry and Drug Discovery in Bath's Department of Life Sciences, Brennan is building an independent research program focused on peptide drug discovery in oncology and infection. He has already introduced new lectures on peptide therapeutics into the pharmacology curriculum, ensuring that the next generation of scientists understands the potential of this modality. His research group continues to expand the TBS platform, working towards new methodological advancements for improved efficacy against a diverse range of protein structures. He is now extending his peptide discovery approaches to explore new ways of disrupting bacterial survival, opening fresh possibilities in the fight against antimicrobial resistance.
For Andrew, the appeal of peptides lies in their ability to tackle targets that have resisted other approaches. His trajectory from coiled coils to cancer therapeutics illustrates how foundational training in peptide structure and biophysics can evolve into translational impact. Read more about Andrew's recent research here.
