Our long-term goal is to elucidate the molecular mechanisms of ribosome assembly in eukaryotic cells and to understand how defects in this process cause bone marrow failure and cancer predisposition. Assembly of the two subunits of the ribosome, containing 80 different ribosomal proteins and four ribosomal RNAs, is an essential, evolutionarily conserved process involving around 200 assembly factors. A major bottleneck in understanding the mechanism of ribosome synthesis is to elucidate the precise function of each of the assembly factors. This is not only a fundamental biological problem, but it is also important for oncogenesis: a novel class of human cancer predisposition disorder has recently emerged that is caused by mutations in components of the ribosome assembly pathway (ribosomopathies). In particular, we discovered that the SBDS gene that is mutated in the leukaemia predisposition disorder Shwachman-Diamond syndrome (SDS) has a key conserved role in maturation of the large ribosomal subunit. My lab combines in vivo genetic approaches in a variety of model organisms with biochemistry and structural biology, using the latest advances in single-particle cryo-electron microscopy in particular.