Expanding ubiquitin biology beyond proteins using AI-designed binders

• PhD

Ubiquitination is one of the key signalling systems in cells and has long been studied as a protein modification. Emerging evidence suggests that ubiquitin can also modify other biomolecules, including glycogen, lipids, small metabolites, and nucleic acids, pointing to a broader layer of cellular regulation. However, these modifications have remain largely unexplored as existing methods lack the specificity and sensitivity required for their detection in cells.

This PhD project will address the challenge by developing AI-designed molecular binders that selectively recognise ubiquitinated non-protein substrates. The student will apply these tools to detect and characterise such modifications in cellular systems, while receiving interdisciplinary training in AI-guided protein design, biochemistry, structural biology, proteomics, and mammalian cell biology, contributing to the development of new approaches in ubiquitin research.

The Komander Lab has been studying the ubiquitin system for over two decades, focusing on how ubiquitin signaling is written, interpreted, and removed in cells. The lab brings together a multidisciplinary team of structural biologists, biochemists, chemists, and cell biologists to investigate the molecular machinery that underpins ubiquitination and its roles in diverse cellular processes.

We use a wide range of complementary approaches, including X-ray crystallography, cryo-electron microscopy, NMR spectroscopy, fluorescence microscopy, cell biology, and quantitative proteomics. By combining structural and functional strategies, we aim to understand how ubiquitin-modifying enzymes operate at a molecular level and how ubiquitin signaling regulates key cellular pathways in health and disease.