“From broken ribosomes to human disease: uncovering how the nucleolus holds the key to new diagnostics and therapies."

Host: Professor Angus Lamond & Professor Liz Miller

Venue: MSI Small Lecture Theatre, SLS

This Seminar is fully funded by external sources 

RNA Molecular Biology, Université libre de Bruxelles (ULB), Fonds de la Recherche Scientifique, Belgium (F.R.S./FNRS)

Ribosome biogenesis is a complex pathway that assembles four ribosomal RNAs with ~80 proteins into two subunits of unequal size, each with specialized functions in translation. Proper ribosome production is critical: too few cause congenital ribosomopathies, while uncontrolled production drives cancer. Ribosome modulators have already entered anticancer clinical trials.

Key steps include the processing of polycistronic pre-rRNAs and their extensive covalent modification. These events serve as powerful readouts of ribosome assembly, revealing defects, defining biomarker signatures of disease, and providing molecular fingerprints that may trace tissue of origin and disease grade.

The nucleolus, where early steps occur, is a biomolecular condensate whose dynamic morphology mirrors function, making it both a stress sensor and a biomarker. Traditional biochemical approaches to study pre-rRNA processing, while robust, require large inputs and lack resolution.

I will present our next-generation sequencing strategies combining short- and long-read technologies to map RNA processing and modification with high sensitivity and resolution. These advances are uncovering the nucleolar blueprint and enabling the use of nucleolar biology as a platform to discover novel modulators of ribosome biogenesis.

By bridging mechanism, disease, and technological developments, we aim to transform our understanding of ribosome biogenesis from a fundamental cellular process into a translational opportunity for diagnostics and therapy.