Louise Walport
Group Leader
Imperial College London and The Francis Crick Institute
Talk Information
New Fronteirs in Peptide Science
19 June 2025, 04:50pm - 05:05pm, in the Pacific Jewel Ballroom
L72 – A Cyclic Peptide Toolkit to Modulate Protein Citrullination
Dr. Louise Walport is a Senior Lecturer in the Department of Chemistry at Imperial College London and a Group Leader at the Francis Crick Institute. Her research focuses on the development of cyclic peptide tools to investigate protein-protein interactions, particularly those involved in epigenetic regulation and immune responses.
Academic Background
Dr. Walport obtained her MChem in Chemistry from Magdalen College, University of Oxford, in 2009. She completed her DPhil in Chemical Biology at the University of Oxford in 2014, working under Professors Chris Schofield and Christina Redfield. Her doctoral research employed biochemical and structural techniques to study 'reader' and 'eraser' proteins involved in epigenetics. Following her Ph.D., she conducted postdoctoral research at Oxford before receiving a Global Marie Skłodowska-Curie Fellowship to work with Professor Hiroaki Suga at the University of Tokyo. She returned to Oxford for a final year of her fellowship in Professor Schofield’s lab. In 2018, Dr. Walport established her independent research group at the Francis Crick Institute, concurrent with her appointment at Imperial College London.
Research Focus
Dr. Walport's laboratory specializes in chemical biology, with an emphasis on designing and utilizing cyclic peptides to probe and modulate protein-protein interactions. Her team employs mRNA display technologies to discover high-affinity cyclic peptides targeting proteins implicated in epigenetic regulation, such as bromodomains and peptidylarginine deiminases, PADIs. This research aims to elucidate the mechanisms of these proteins and develop novel therapeutic strategies.
Notable Contributions
Dr. Walport has significantly advanced the understanding of protein-protein interactions through her development of cyclic peptide inhibitors. Her work includes the discovery of covalent cyclic peptide inhibitors of PADI4 using mRNA-display with genetically encoded electrophilic warheads, as well as the identification of cyclic peptides targeting the BRD3 extraterminal domain. These contributions have provided valuable insights into the regulation of epigenetic enzymes and their roles in disease.
Professional Engagements
Beyond her research, Dr. Walport is actively involved in teaching and mentoring at Imperial College London. She contributes to the scientific community through her participation in conferences and collaborative projects. Her interdisciplinary approach bridges chemistry and biology, fostering innovations in the development of chemical tools for biomedical research.
Through her pioneering work in chemical biology, Dr. Louise Walport continues to make significant contributions to the understanding and manipulation of protein interactions, with implications for therapeutic development.
A Cyclic Peptide Toolkit to Modulate Protein Citrullination
1The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK; 2Imperial College London, Department of Chemistry, London, W12 0BZ, UK
Peptidyl arginine deiminase IV, PADI4, catalyses the citrullination of a wide range of substrates, with roles in neutrophil extracellular trap formation, chemokine signalling and establishment of pluripotency. Aberrant activity is implicated in a range of pathologies, including rheumatoid arthritis, multiple sclerosis, and various cancers, with emerging evidence suggesting PADI4 inhibition has significant therapeutic potential.
Despite its clear therapeutic potential, key questions remain around its cellular regulation and activation.
To provide new tools to understand PADI4 function we have developed a set of cell permeable, potent and selective cyclic peptide modulators of PADI4. We employed the RaPID, Random non-standard Peptide Integrated Discovery, system to isolate binders of PADI4 from starting libraries of up to 1013 genetically-barcoded cyclic peptides. From three parallel screens designed to target different protein conformations, we identified a series of nanomolar PADI4 peptide binders, with diverse activities. In addition to a potent cell permeable PADI4 inhibitor, we identified first-in-class activators of PADI4 to low calcium conditions both in vitro and in cells. Structures of activator-bound PADI4 reveal an allosteric binding site that may also be important for physiological PADI activation.
We subsequently adapted the RaPID platform to identify covalent cyclic peptides, allowing identification of potent covalent cyclic peptide inhibitors of PADI4 and most recently, photoswitchable inhibitors of a related protein. Together, the peptides provide a powerful toolkit for further elucidation of the function of PADI4 in both normal development and disease, with potential to provide a basis for downstream drug development.