Richard Bayliss
Professor of Molecular Medicine
University of Leeds
Talk Information
Session 7: Protein Modification, Structural Insights, and Disease State
18 June 2025, 09:30am - 09:45am, in the Pacific Jewel Ballroom
L38 – Hydrocarbon-Stapled Peptidomimetic of TACC3 Disrupts CHC Interaction and Delays Mitotic Progression
Professor Richard Bayliss is a renowned molecular biologist specializing in cancer biology and structural molecular medicine. He currently serves as a Professor of Molecular Medicine at the University of Leeds and is a member of the Astbury Centre for Structural Molecular Biology. His research focuses on understanding the molecular mechanisms that underpin cellular functions and how these processes are altered in diseases such as cancer.
Academic Background
Professor Bayliss earned a first-class honors degree in Natural Sciences from the University of Cambridge in 1997, specializing in biological, organic, and theoretical chemistry. He completed his Ph.D. in molecular biology at the MRC Laboratory of Molecular Biology in Cambridge in 2000. Following his doctoral studies, he held postdoctoral positions at the European Molecular Biology Laboratory in Heidelberg, Germany, and at Birkbeck College, London. He established his independent research group at the Institute of Cancer Research in London in 2006. In 2011, he moved to the University of Leicester as a Reader in the Department of Biochemistry and was promoted to Professor in 2014. Professor Bayliss joined the University of Leeds in 2016.
Research Focus
Professor Bayliss's research aims to elucidate the molecular mechanisms that cause disease and to develop new or improved therapies. His work encompasses several key areas:
- Dynamic Protein Interactions: Investigating the transient interactions between proteins that are crucial for cellular processes such as mitosis and nuclear transport.
- Protein Kinases and Cancer Drug Discovery: Studying the structural mechanisms of kinase regulation and developing inhibitors as potential cancer therapeutics.
- Cancer Signaling Pathways: Exploring signaling processes that underpin cancer cell proliferation and survival, including the study of EML4-ALK fusion oncoproteins in non-small cell lung cancer.
- Cell Division: Examining the assembly and function of the mitotic spindle and the role of microtubules in chromosome segregation.
His research integrates structural, computational, and cell biology approaches to understand how protein interactions are regulated and how they can be targeted in disease contexts.
Notable Publications
Targeting ERBB3 and AKT to overcome adaptive resistance in EML4-ALK-driven non-small cell lung cancer, Cell Death & Disease, 2024.
Exploring the dynamics and interactions of the N-myc transactivation domain through solution nuclear magnetic resonance spectroscopy, Biochemical Journal, 2024.
CEP192 localises mitotic Aurora-A activity by priming its interaction with TPX2, EMBO Journal, 2024.
Structural features of the protein kinase domain and targeted binding by small-molecule inhibitors, Journal of Biological Chemistry, 2022.
These publications highlight Professor Bayliss's contributions to understanding protein structures and interactions, particularly in the context of cancer biology and therapeutic development.
Professional Engagements
Professor Bayliss is actively involved in collaborative research projects and has secured funding from organizations such as the BBSRC, MRC, and Cancer Research UK. He has served as the Head of the School of Molecular and Cellular Biology at the University of Leeds and is a lead investigator in the CHORAL, Children's Cancer Translational Research, initiative, aiming to improve outcomes for children and young people living with and beyond cancer.
Through his extensive research and leadership, Professor Richard Bayliss continues to make significant contributions to the field of molecular medicine, advancing our understanding of cancer biology and informing the development of targeted therapies.
Hydrocarbon-Stapled Peptidomimetic of TACC3 Disrupts CHC Interaction and Delays Mitotic Progression
School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom
The complex formed by Transforming Acidic Coiled Coil 3 (TACC3) and Clathrin Heavy Chain (CHC) enhances mitotic spindle stability by cross-linking k-fibres1. Previously, we elucidated the structural basis of the TACC3/CHC interaction, which is driven by hydrophobic residues on both proteins and the formation of a helix in TACC3 that docks into the helical repeats of CHC2. The interaction is also dependent on phosphorylation of TACC3 at S558 by Aurora-A. Here we find that this phosphorylation event plays an unusual role in a protein-protein interaction by overcoming the electrostatic repulsion between Lys507 of CHC and basic residues in TACC3.
Leveraging this insight, we optimized the sequence using peptide arrays to develop a hydrocarbon-stapled peptide (SP-TACC3) that binds CHC with over a hundred-fold higher affinity than the native peptide, effectively disrupting the interaction. The crystal structure of the SP-TACC3/CHC complex reveals the basis for the enhanced interaction and highlights the contribution of additional polar and hydrophobic interactions. SP-TACC3 efficiently penetrates cells and displaces TACC3 from the mitotic spindle, causing a delay in mitotic progression in two out of three cancer cell lines. This work showcases the novel application of hydrocarbon-stapled peptides to disrupt the TACC3-CHC protein-protein interaction in a cellular context, highlighting the potential of targeting this interface for future cancer therapies.
1. Hood FE et al. J. Cell Biol. 2013 202:463-78
2. Burgess SG et al. EMBO J. 2018 37. e97902