Developing 4D Photo-Cross-Linking Mass Spectrometry to Map the Dynamic Proteome in Health and Disease

About the project

About the Project Proteins rarely act in isolation. Understanding how they fold, assemble, and interact in the crowded environment of living cells is essential for uncovering the molecular basis of health and disease. While recent advances in photo-cross-linking mass spectrometry (photo-XL-MS) have allowed us to map protein interactomes and structural conformations at near-atomic spatial resolution, living systems are inherently dynamic. This PhD project aims to push the boundaries of chemical biology by adding a temporal dimension to spatial interactomics . By integrating time-resolved photo-cross-linking with high-resolution quantitative mass spectrometry, you will create 4D molecular movies of protein networks inside living cells, capturing transient structural transitions and fleeting interactions as they happen. Selected recent publications: Jiang, Y., Zhao, R., Mao, P. et al. Inherent MS-cleavability of diazirine photo-cross-links enables residue-level structural analysis. Nat. Commun. 17 , 6558 (2026). https://doi.org/10.1038/s41467-026-73272-0 Zhao, L., Zhao, R., Gong, Z. et al. In-situ cross-linking mass spectrometry reveals compartment-specific proteasomal interactions and structural heterogeneity. Nat. Commun. 16 , 10725 (2025). https://doi.org/10.1038/s41467-025-65752-6 Jiang, Y., Zhang, X., Nie, H. et al. Dissecting diazirine photo-reaction mechanism for protein residue-specific cross-linking and distance mapping. Nat. Commun . 15 , 6060 (2024). https://doi.org/10.1038/s41467-024-50315-y Research groups: http://www.tanglab.cn http://tanglab.pku.edu.cn

Research areas