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The Department's buildings are currently open for wet laboratory work only. We have carried out a comprehensive COVID-19 risk assessment process and have introduced a number of new measures to ensure the safety of our staff, including reduced building occupancy, strict social distancing, 'family'-based working, and increased cleaning and hygiene regimes. All staff who can work remotely will do so for the foreseeable future. Please continue to contact us by email until further notice.

Department of Biochemistry

 
Tom Blundell

Understanding in space and time multicomponent systems involved in cell regulation and targeting them in cancer and mycobacterial infections.

 

The Blundell Group focuses on structural and computational biology and their applications to drug discovery. The experimental research seeks to understand multicomponent cell-regulatory systems, currently DNA repair through non-homologous end joining. The Group, which has defined the structure of the 4000-amino-acid kinase DNA-PKcs and discovered an important new component PAXX, is currently investigating their interactions using cryo-EM. The Blundell Group has also produced widely used software packages, including Modeller (~11,200 citations) and Fugue (~1,400 citations) for protein modelling, and SDM and mCSM for predicting effects of mutations on protein stability and interactions. The Group now focuses on machine learning as well as databases to underpin drug discovery and to understand cancer and drug resistance. Blundell has developed new approaches to structure-guided and fragment-based drug discovery in Astex Therapeutics, now with breast cancer and urothelial carcinoma drugs on market. In academia, he has targeted Mycobacterium tuberculosis proteins in the Gates HIT-TB consortium, M. leprae for the American Leprosy Mission and M. abscessus for the Cystic Fibrosis Trust.

 

Research objectives

  • How is selectivity achieved through multicomponent, cell regulatory systems?

  • How can cryo-EM be optimised for structural biology of such complex multicomponent assemblies?

  • How can we use machine learning to understand protein-ligand interactions and the impacts of mutations on function?

  • How can fragment-based, structure-guided drug discovery be best used to fight mycobacterial infections?

 

Key publications

Wang JL, Duboc C, Wu Q, Ochi T, Liang S, Tsutakawa SE, Lees-Miller SP, Nadal M, Tainer JA, Blundell TL, Strick TR (2018). Dissection of DNA double-strand-break repair using novel single-molecule forceps. Nat. Struct. Mol. Biol., 25(6):482-487. doi: 10.1038/s41594-018-0065-1

Sibanda BL, Chirgadze DY, Ascher DB, Blundell TL (2017). DNA-PKcs structure suggests an allosteric mechanism modulating DNA double-strand break repair. Science, 355(6324):520-524. doi: 10.1126/science.aak9654

Mendes V, Blundell TL (2017). Targeting tuberculosis using structure-guided fragment-based drug design. Drug Discov. Today, 22(3):546-554. doi: 10.1016/j.drudis.2016.10.003

Ochi T, Blackford AN, Coates J, Jhujh S, Mehmood S, Tamura N, Travers J, Wu Q, Draviam VM, Robinson CV, Blundell TL, Jackson SP (2015). PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair. Science, 347(6218):185-188. doi: 10.1126/science.1261971

Hepburn L, Prajsnar TK, Klapholz C, Moreno P, Loynes CA, Ogryzko NV, Brown K, Schiebler M, Hegyi K, Antrobus R, Hammond KL, Connolly J, Ochoa B, Bryant C, Otto M, Surewaard B, Seneviratne SL, Grogono DM, Cachat J, Ny T, Kaser A, Török ME, Peacock SJ, Holden M, Blundell T, Wang L, Ligoxygakis P, Minichiello L, Woods CG, Foster SJ, Renshaw SA, Floto RA (2014). A Spaetzle-like role for nerve growth factor β in vertebrate immunity to Staphylococcus aureus. Science, 346(6209):641-646. doi: 10.1126/science.1258705

Contact details

Secretary  Nicola Miller (Secretary)​

Email  njm44@cam.ac.uk

Location  Sanger Building

Opportunities

The Blundell Group is not currently accepting enquiries from prospective students or staff.