Professor of Haematology
Home page: https://www.cimr.cam.ac.uk/staff/professor-alan-j-warren-fmedsci
Description of research
Ribosomes are the universally conserved macromolecular machines that decode the mRNA to make proteins. However, it remains unclear how these large ribonucleoprotein particles are assembled. Defects in the ribosome assembly process cause the ‘ribosomopathies’, a fascinating new group of human developmental disorders that perturb haematopoietic stem cell function and promote progression to bone marrow failure, myelodysplastic syndrome and acute leukaemia. Our research on the mechanisms of ribosome assembly centres around the ribosomopathies with Shwachman-Diamond syndrome currently a key focus for us.
The key questions that underpin our current research are: what are the mechanisms of eukaryotic ribosome assembly; how is this process regulated and monitored; what are the cellular consequences of defective ribosome biogenesis; how do defects in this process cause human disease? My laboratory uses a highly interdisciplinary approach that combines genetics, biochemistry and high-resolution structural studies, with a particular focus on single-particle cryo-electron microscopy.
Keywords: Ribosome biogenesis, Stem cells, Genetics, Structural biology, RNA processing
Clinical conditions: Myelodysplastic syndromes, Leukaemia, Inherited bone marrow failure syndromes, Shwachman-Diamond syndrome, Poikiloderma with neutropenia
Methodologies: Model organisms (Drosophila, yeast, Dictyostelium), mammalian genetics, confocal microscopy, X-ray crystallography, NMR spectroscopy, Cryo-EM, protein expression and purification, molecular biology, biochemistry