Laboratory of RNA Structural Biology and Biochemistry: where molecular machines meet evolutionary insight

Created in October 2024 by Prof. Arnaud Vanden Broeck within the Integrative Biological Sciences and Centre for Protein Engineering (InBioS – CIP) research units at the University of Liège, the Laboratory of RNA Structural Biology and Biochemistry (RSBB) explores the fascinating world of divergent molecular machines through cryogenic electron microscopy (cryo-EM). With a dual focus on human health and evolutionary structural biology, the lab aims to uncover how unique RNA processing pathways operate in parasites and what they reveal about the diversity of gene expression mechanisms across eukaryotes.

Headed by Prof. Vanden Broeck, Principal Investigator and FNRS Research Associate, the laboratory currently includes a PhD student and a postdoctoral researcher, with the team expected to double by early 2026. Supported by two major sources of funding: a five-year ERC Starting Grant and a two-year FNRS MISU grant – the lab benefits from a budget of €2.5 million in public funding to kickstart its research activities.

Prof. Vanden Broeck trained as a structural biologist at the University of Strasbourg and later spent six years as a postdoctoral fellow at Rockefeller University in New York. There, he studied the human ribosome, the protein-synthesizing factory of cells, using cryo-EM and genome editing. His research unveiled the early stages of ribosome assembly and how defects in this process contribute to cancer and rare developmental disorders called ribosomopathies. Upon returning to Belgium, Prof. Vanden Broeck broadened his focus to include kinetoplastid parasites such as Trypanosoma and Leishmania, which cause neglected tropical diseases transmitted by insects. These organisms use highly unusual gene expression pathways, providing a unique opportunity to understand both disease mechanisms and molecular evolution.

Thanks to ERC funding, the lab is currently investigating RNA trans-splicing, a process that fuses two separate RNA molecules to generate mature messenger RNAs—a hallmark of kinetoplastid biology. This process is carried out by the trans-spliceosome, a large ribonucleoprotein complex that the team aims to reconstruct in 3D at atomic resolution using cryo-EM and AI-based interactomics. By capturing its successive functional states, the goal is to uncover potential therapeutic targets and shed light on how molecular complexity evolves in divergent eukaryotes.