Understanding ribosome biogenesis in mammalian cells has become more urgent with the discovery of an increasing list of human genetic diseases linked to defects in ribosome production. The mutated genes encode ribosomal proteins, like in Diamond Blackfan anemia, or pre-ribosomal factors like in the Shwachman-Diamond syndrome or the Treacher-Collins syndrome. Similarly, 5q- myelodyplasia are linked to haploinsufficiency of ribosomal protein RPS14. The cellular stress resulting from defective ribosome biogenesis triggers response pathways, including p53 activation and cell cycle arrest, that appear to be fatal to some physiological processes. In contrast, activating ribosomal stress appears as a promising strategy for cancer therapy. Our group has pioneered the study of ribosome biogenesis defects in Diamond Blackfan anemia and characterized the functional impact of mutations found in DBA patient in collaboration with Hanna Gazda (Boston Children Hospital) and Lydie Da Costa (Hopital Robert Debré, Paris). We are currently pursuing this work within the EuroDBA european consortium network (e-RARE program). We also have an ongoing collaboration with Patrick Blader's group at CBI to study the impact of some mutations on zebrafish development.
A quick video in French presenting DBA : https://youtu.be/ipJ8QrGIaAA