Professor Alan Warren

University of Cambridge

University departments
Department of Haematology
University institutes
Cambridge Institute for Medical Research
NHS or other affiliations
Haematology

Position: Professor
Personal home page: http://www.cimr.cam.ac.uk/research/principal-investigators/principal-investigators-q-z/warren

PubMed journal articles - click here

Professor Alan Warren is pleased to consider applications from prospective PhD students.

Research description

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.

Research Programme
Haematological Malignancies
Methods and technologies
Cell culture
Computational modelling
Confocal microscopy
Fluorescence microscopy
HPLC/FPLC
Imaging
In vivo modelling
Microscopy
Model organisms
PCR
Protein biochemistry
Protein purification
Proteomics
Recombinant protein expression
X-ray crystallography
Tumour type interests
Leukemia
Keywords
leukaemia
bone marrow failure
ribosome
ajw1000
Recent publications:
 Retrieving latest data from feed...

Symplectic Elements feed provided by Research Information, University of Cambridge


Key publications

Weis F, Giudice E, Churcher M, Jin L, Hilcenko C, Wong CC, Traynor D, Kay RR, Warren AJ. Mechanism of eIF6 release from the nascent 60S ribosomal subunit. Nat Struct Mol Biol, (2015) Nov;22(11):914-9. doi: 10.1038/nsmb.3112. Epub 2015 Oct 19. PMID: 26479198.

Wong CC, Traynor D, Basse N, Kay RR, Warren AJ. Defective ribosome assembly in Shwachman- Diamond syndrome. Plenary Paper, Blood. 2011 Oct 20;118(16):4305-12. doi: 10.1182/blood-2011-06- 353938. Epub 2011 Jul 29. PMID: 21803848  

Finch AJ, Hilcenko C, Basse N, Drynan LF, Goyenechea B, Menne TF, González Fernández Á, Simpson P, D?Santos CS, Arends MJ, Donadieu J, Bellanné-Chantelot C, Costanzo M, Boone C, McKenzie AN, Freund SM, Warren AJ. Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome. Genes and Development (2011) 25: 917-929. PMID: 21536732  

Menne TM, Goyenechea B, Sánchez-Puig N, Wong CC, Tonkin LM, Ancliff P, Brost RL, Costanzo M, Boone C and Warren AJ. The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast. Nature Genetics (2007) 39: 486-95.   

SBDS (magenta) and the GTPase EFL1 (blue) co-catalyse eviction of the anti-association factor eIF6 (yellow) to license the entry of mature ribosomal subunits into active translation.