skip to content

MRC Toxicology Unit

 

Unit Programme:  Post-transcriptional control of gene expression following toxic injury

Programme Leader: Professor Anne Willis OBE

 

Anne’s research in the Unit is directed towards understanding the role of post-transcriptional control in response to toxic injury with a focus on RNA-binding proteins, regulatory RNA motifs and tRNAs. Through our mechanistic research we are developing predictive adverse outcome models that can be shared with our industrial partners, in particular we are working to understand the “off target” effects of new modalities such as therapeutic RNAs. In addition to her Unit programme, Anne holds a Wellcome Trust investigator award (jointly with Professor Kathryn Lilley in Biochemistry) to research into the processes that drive localised mRNA translation, a Wellcome Trust collaborative grant to study the role of mRNA translation elongation control in health and disease, with additional funding from BBSRC, Bloodwise and Cancer Research Technologies (as part of translational alliance with industry).

 

Key Publications

Chernova T, Murphy FA, Galavotti S, Sun XM, Powley IR, Grosso S, Schinwald A, Zacarias-Cabeza J, Dudek KM, Dinsdale D, Le Quesne J, Bennett J, Nakas A, Greaves P, Poland CA, Donaldson K, Bushell M, Willis AE, MacFarlane M. (2017) Long-Fiber Carbon Nanotubes Replicate Asbestos-Induced Mesothelioma with Disruption of the Tumor Suppressor Gene Cdkn2a (Ink4a/Arf). Curr Biol. 2017 27:3302-3314.e6. doi: 10.1016/j.cub.2017.09.007.

 

Bastide A, Peretti D, Knight JR, Grosso S, Spriggs RV, Pichon X, Sbarrato T, Roobol A, Roobol J, Vito D, Bushell M, von der Haar T, Smales CM, Mallucci GR, Willis AE. (2017) RTN3 Is a Novel Cold-Induced Protein and Mediates Neuroprotective Effects of RBM3. Curr Biol. 2017 27:638-650. doi: 10.1016/j.cub.2017.01.047.

 

Somers J, Wilson LA, Kilday JP, Horvilleur E, Cannell IG, Pöyry TA, Cobbold LC, Kondrashov A, Knight JR, Puget S, Grill J, Grundy RG, Bushell M, Willis AE. (2015) A common polymorphism in the 5' UTR of ERCC5 creates an upstream ORF that confers resistance to platinum-based chemotherapy. Genes Dev. 29:1891-6. doi: 10.1101/gad.261867.115.

 

Peretti D, Bastide A, Radford H, Verity N, Molloy C, Martin MG, Moreno JA, Steinert JR, Willis AE, Mallucci GR. (2015) RBM3 mediates structural plasticity and protective effects of cooling in neurodegeneration. Nature. 518:236-9

 

Faller WJ, Jackson TJ, Knight JR, Ridgway RA, Jamieson T, Karim SA, Jones C, Radulescu S, ….Willis AE, Sansom OJ. (2015) mTORC1-mediated translational elongation limits intestinal tumour initiation and growth. Nature 517:497-500.

 

Horvilleur E, Sbarrato T, Hill K, Screen M, Goodrem PJ, Spriggs RV, Sawicka K, Chaplin LC, Packham G, Potter N, Dirnhofer S, Tzankov A, Dyer MJS, Bushell M, MacFarlane M and Willis. A.E. (2014) A role for eukaryotic initiation factor 4B overexpression in the pathogenesis of diffuse large B-cell lymphoma Leukemia. 28:1092-102

 

King HA, Cobbold LC, Pichon X, Pöyry T, Wilson LA, Booden H, Jukes-Jones R, Cain K, Lilley KS, Bushell M, Willis AE (2014) Remodelling of a polypyrimidine tract-binding protein complex during apoptosis activates cellular IRESs. Cell Death Differ. 21:161-71. doi: 10.1038/cdd.2013.135

 

Meijer HA, Kong YW, Lu WT, Wilczynska A, Spriggs RV, Robinson SW, Godfrey JD, Willis AE, Bushell M. (2013) Translational repression and eIF4A2 activity are critical for microRNA-mediated gene regulation. Science. 340:82-5. doi: 10.1126/science.1231197

 

Spriggs KA, Bushell M, Willis AE (2010) Translational regulation of gene expression during conditions of cell stress. Mol Cell. 40:228-37. doi: 10.1016/j.molcel.2010.09.028

 

Powley IR, Kondrashov A, Young LA, Dobbyn HC, Hill K, Cannell IG, Stoneley M, Kong YW, Cotes JA, Smith GC, Wek R, Hayes C, Gant TW, Spriggs KA, Bushell M, Willis AE. 2009 Translational reprogramming following UVB irradiation is mediated by DNA-PKcs and allows selective recruitment to the polysomes of mRNAs encoding DNA repair enzymes. Genes Dev. 2009 23:1207-20. doi: 10.1101/gad.516509.