Molecular mechanisms of eukaryotic ribosome biogenesis

We aim to identify pathways that when perturbed result in the development of life-threatening cancers of the blood such as myelodysplasia and acute leukaemia. Our long term goal is to use this information to design new approaches to the treatment of these devastating cancers of the blood. Recent exciting data link the origins of inherited and acquired forms of blood cancer to defects in so-called "housekeeping" processes in our cells, specifically in the assembly of the machines (called ribosomes) that make proteins. A major focus of our work is to understand in detail how ribosomes are put together from their component parts. To do this, we are learning about the three-dimensional shape of some of the key proteins involved and trying to undersrand how these proteins work together to assemble mature ribosomes. In addition to experiments in the test tube, we are also using a range of model organisms to determine the role of specific ribosome assembly factors in living cells. The fundamental insights that we hope to obtain will not only provide a deeper understanding of the fundamental mechanisms underlying the process of ribosome assembly, but will also help improve the diagnosis and long-term outlook for patients affected by disorders of ribosome synthesis and, more generally, for patients affected by cancer.