Rational and precise targeting of oncogene-driven signalling remains a major and unresolved challenge in cancer research. A detailed understanding of the structural and molecular mechanisms underlying oncogene activation and signalling is essential for the development of more effective and selective therapeutics. Our research focuses on the molecular principles governing protein kinase function, including how kinases are activated and regulated through post-translational modifications and allosteric mechanisms, and how they assemble into macromolecular complexes to transmit signals within the cell. We place particular emphasis on how these regulatory processes are disrupted in cancer by oncogenic mutations and aberrant signalling events. Importantly, this atomic-level understanding provides a foundation for the rational design of next-generation protein kinase inhibitors, enabling more precise and personalised therapeutic strategies.

To address these questions, we employ an integrated and multidisciplinary approach that combines molecular biology for construct design, protein biochemistry and biophysics for protein production and functional characterisation, and mass spectrometry for the identification and quantification of post-translational modifications. Structural insights are obtained through X-ray crystallography, XL-MS, and electron microscopy, allowing high-resolution visualisation of protein architecture and dynamics. Functional validation is performed using in vivo models such as Drosophila. In parallel, we apply structure-guided drug discovery approaches, including molecular docking and molecular dynamics simulations, to identify and exploit structural and functional vulnerabilities for the development of novel therapeutic agents.