BSc Biochemistry(Cardiff University)

PhD ProteinEngineering (Bristol University) 

I began my science career studying protein engineering under Professor J. John Holbrook at the Bristol University. During these studies I developing 2 approaches to enzyme engineering based on forced evolution and rational design. I moved to a PDRA position in the laboratory of Professor Robin Carrell FRS in the Cambridge Institute of Medical Research. Working with Dr Arthur Lesk I studied the mechanism of action of a class of serine proteinase inhibitors (SERPINS) involved in innate immunity and blood clotting. During this time I defined a mechanistic and structural explanation which underlies a group of diseases known as serpinopathies. In 2003 I was awarded a prestigious MRC Career development fellowship to continue my work on the SERPINS, as part of this I worked with Professor Alison Rodger (Warwick) to establish Linear Dichroism as an important technique for the study of membrane proteins and protein fibres. More recently I have developed three research strands all enabled by linear dichroism. Firstly I have produced insights into the assemblies that underlie bacterial cell division. Secondly I have developed a novel method that trivializes the production of membrane proteins enabling advances in bioprocessing. Finally I have developed a platform bioassay that represents one of the first commercial applications of synthetic biology.

Impact has become a keyword in British science, my teaching aims to embed an impact ethos at the earliest stages of undergraduate and postgraduate training. I believe this can be achieved by first highlighting the wonders of the biological science and then showing how anyone can commercialize science for the common good.

Over the past 2 billion years life has been evolving to produce the wonderful biological diversity we see today. At the molecular level evolution has produced nano-molecular machines of wonderful complexity. My research is focused upon studying these wonders, understanding how they assemble and harnessing their function for good. Currently my studies have three streams of research:

1. Studying and understanding the complex molecular machinery that underlies bacterial cell division.
2. Developing novel nanoencapsulation methods that allow large scale production of membrane proteins.
3. Building nano-assemblies that can be used in detection systems

The last 2 of theseprojects have provided 7 patents that are currently the focus of two commercialisation projects.

I take a keen interest in wider aspects of science policy being a member of Senate at the University of Birmingham and a member of Council at the Biochemical Society. When not working I spend time watching my sons play rugby, rebuilding classic cars and sleeping.

2010-2005

1. Mardakheh FK, Auciello G, Dafforn TR, Rappoport JZ, Heath JK. Nbr1 is a novel inhibitor of ligand-mediated receptor tyrosine kinase degradation. 2010 Mol Cell Biol.;30(24):5672-85. 

2. Soufi A, Sawasdichai A, Shukla A, Noy P, Dafforn TR, Smith C, Jayaraman PS, Gaston K. DNA compaction by the higher-order assembly of PRH/Hex homeodomain protein oligomers. 2010 Nucleic Acids Res. 2010 Nov 1;38(21):7513-25. 

3. Damianoglou A, Rodger A, Pridmore C, Dafforn TR, Mosely JA, Sanderson JM, Hicks MR. The synergistic action of melittin and phospholipase A2 with lipid membranes: development of linear dichroism for membrane-insertion kinetics. 2010 Protein Pept Lett.;17(11):1351-62.

4. Bromley EH, Channon KJ, King PJ, Mahmoud ZN, Banwell EF, Butler MF, Crump MP, Dafforn TR, Hicks MR, Hirst JD, Rodger A, Woolfson DN. Assembly pathway of a designed alpha-helical protein fiber. Biophys J. 2010 Apr 21;98(8):1668-76.

5. Marshall KE, Hicks MR, Williams TL, Hoffmann SV, Rodger A, Dafforn TR, Serpell LC. 2010 Characterizing the assembly of the Sup35 yeast prion fragment, GNNQQNY: structural changes accompany a fiber-to-crystal switch. Biophys J. 2010 Jan 20;98(2):330-8.

6. Cao X, Coskun U, Rössle M, Buschhorn SB, Grzybek M, Dafforn TR, Lenoir M, Overduin M, Simons K.  Golgi protein FAPP2 tubulates membranes. 2009 Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21121-5. 

7. Hicks MR, Dafforn TR, Damianoglou A, Wormell P, Rodger A, Hoffmann SV.  2009 Synchrotron radiation linear dichroism spectroscopy of the antibiotic peptide gramicidin in lipid membranes. Analyst. 2009 Aug;134(8):1623-8. 

8. Kosmoliaptsis V, Chaudhry AN, Sharples LD, Halsall DJ, Dafforn TR, Bradley JA, Taylor CJ. 2009 Predicting HLA class I alloantigen immunogenicity from the number and physiochemical properties of amino acid polymorphisms. Transplantation. Sep 27;88(6):791-8.

9. Bulheller BM, Rodger A, Hicks MR, Dafforn TR, Serpell LC, Marshall KE, Bromley EH, King PJ, Channon KJ, Woolfson DN, Hirst JD. 2009, Flow linear dichroism of some prototypical proteins. J Am Chem Soc. Sep 23;131(37):13305-14.

10. Lawson AJ, Walker EA, White SA, Dafforn TR, Stewart PM, Ride JP. 2009, Mutations of key hydrophobic surface residues of 11 beta-hydroxysteroid dehydrogenase type 1 increase solubility and monodispersity in a bacterial expression system. Protein Sci.  Jul;18(7):1552-63.

11. Knowles, TJ, R Finka, C Smith, YP Lin, T Dafforn, M Overduin, 2009, Membrane proteins solubilized intact in lipid containing nanoparticles bounded by styrene maleic acid copolymer, J Amer Chem Soc, 131(22):7484-5 

12. Lawson AJ, Walker EA, White SA, Dafforn TR, Stewart PM, Ride JP. 2009. Mutations of key hydrophobic surface residues of 11beta-hydroxysteroid dehydrogenase type 1 increase solubility and monodispersity in a bacterial expression system. Protein Sci. 2009 Apr 29. [Epub ahead of print] 

13. Nicholls S, Piper KP, Mohammed F, Dafforn TR, Tenzer S, Salim M, Mahendra P, Craddock C, van Endert P, Schild H, Cobbold M, Engelhard VH, Moss PA, Willcox BE. Secondary anchor polymorphism in the HA-1 minor histocompatibility antigen critically affects MHC stability and TCR recognition. PNAS USA. 2009. 106(10):3889-94. 

14. Kami K, Chidgey M, Dafforn T, Overduin M. The desmoglein-specific cytoplasmic region is intrinsically disordered in solution and interacts with multiple desmosomal protein partners. J Mol Biol. 2009;386(2):531-43. 

15. Conner M, Hicks MR, Dafforn T, Knowles TJ, Ludwig C, Staddon S, Overduin M, Günther UL, Thome J, Wheatley M, Poyner DR, Conner AC. Functional and biophysical analysis of the C-terminus of the CGRP-receptor; a family B GPCR. Biochem.2008: 47(32):8434-44.

16. Ennaceur SM, Hicks MR, Pridmore CJ, Dafforn TR, Rodger A, Sanderson JM. Peptide adsorption to lipid bilayers: slow processes revealed by linear dichroism spectroscopy. Biophys J. 2009;96(4):1399-407. 

17. Batt SM, Bingle LE, Dafforn TR, Thomas CM. Bacterial genome partitioning: N-terminal domain of IncC protein encoded by broad-host-range plasmid RK2 modulates oligomerisation and DNA binding. J Mol Biol. 2009;385(5):1361-74.

18. McCrudden, M.T., T.R. Dafforn, D.F. Houston, P.T. Turkington, and D.J. Timson, Functional domains of the human epididymal protease inhibitor, eppin Febs J, 2008. 275(8): p. 1742-1750.

19. Dicko C, Hicks MR, Dafforn TR, Vollrath F, Rodger A, Hoffmann SV. Breaking the 200 nm limit for routine flow linear dichroism measurements using UV synchrotron radiation. Biophys J. 2008;95(12):5974-7.

20. Hicks MR, Damianoglou A, Rodger A, Dafforn TR. Folding and membrane insertion of the pore-forming peptide gramicidin occur as a concerted process. J Mol Biol. 2008 ;383(2):358-66. 

 

21. Oates J, Hicks M, Dafforn TR, DiMaio D, Dixon AM. In vitro dimerization of the bovine papillomavirus E5 protein transmembrane domain. Biochemistry. 2008 ;47(34):8985-92. 

22. Jamshad, M., S. Rajesh, Z. Stamataki, J.A. McKeating, T. Dafforn, M. Overduin, and R.M. Bill, Structural characterization of recombinant human CD81 produced in Pichia pastoris Protein Expr Purif, 2008. 57(2): p. 206-16.

23. Small, E., R. Marrington, A. Rodger, D.J. Scott, K. Sloan, D. Roper, T.R. Dafforn, and S.G. Addinall, FtsZ polymer-bundling by the Escherichia coli ZapA orthologue, YgfE, involves a conformational change in bound GTP J Mol Biol, 2007. 369(1): p. 210-21

24. Obiozo, U.M., T.H. Brondijk, A.J. White, G.V. Boxel, T.R. Dafforn, S.A. White, and J.B. Jackson, Substitution of tyrosine-146 in the dI component of proton-translocating transhydrogenase leads to reversible dissociation of the active dimer into inactive monomers J Biol Chem, 2007, 282(50):36434-43

25. Dafforn, T.R., So how do you know you have a macromolecular complex? Acta Crystallogr D Biol Crystallogr, 2007. 63(Pt 1): p. 17-25.

26. Brissett, N.C., R.S. Pitcher, R. Juarez, A.J. Picher, A.J. Green, T.R. Dafforn, G.C. Fox, L. Blanco, and A.J. Doherty, Structure of a NHEJ polymerase-mediated DNA synaptic complex Science, 2007. 318(5849): p. 456-9.Bhakta, T., S.J. Whitehead, J.S. Snaith, T.R. Dafforn, J. Wilkie, S. Rajesh, S.A. White, and J.B. Jackson, Structures of the dI2dIII1 complex of proton-translocating transhydrogenase with bound, inactive analogues of NADH and NADPH reveal active site geometries Biochemistry, 2007. 46(11): p. 3304-18.

27. Rodger, A., R. Marrington, M.A. Geeves, M. Hicks, L. de Alwis, D.J. Halsall, and T.R. Dafforn, Looking at long molecules in solution: what happens when they are subjected to Couette flow? Phys Chem Chem Phys, 2006. 8(27): p. 3161-71.

28. Robertson, A.S., D. Belorgey, D. Gubb, T.R. Dafforn, and D.A. Lomas, Inhibitory activity of the Drosophila melanogaster serpin Necrotic is dependent on lysine residues in the D-helix J Biol Chem, 2006. 281(36): p. 26437-43.

29. Pelte, N., A.S. Robertson, Z. Zou, D. Belorgey, T.R. Dafforn, H. Jiang, D. Lomas, J.M. Reichhart, and D. Gubb, Immune challenge induces N-terminal cleavage of the Drosophila serpin Necrotic Insect Biochem Mol Biol, 2006. 36(1): p. 37-46.

30. Hicks, M.R., A. Rodger, C.M. Thomas, S.M. Batt, and T.R. Dafforn, Restriction enzyme kinetics monitored by UV linear dichroism Biochemistry, 2006. 45(29): p. 8912-7.

31. Alderwick, L.J., V. Molle, L. Kremer, A.J. Cozzone, T.R. Dafforn, G.S. Besra, and K. Futterer, Molecular structure of EmbR, a response element of Ser/Thr kinase signaling in Mycobacterium tuberculosis PNAS U S A, 2006. 103(8): p. 2558-63.

32. Millard, T.H., G. Bompard, M.Y. Heung, T.R. Dafforn, D.J. Scott, L.M. Machesky, and K. Futterer, Structural basis of filopodia formation induced by the IRSp53/MIM homology domain of human IRSp53 Embo J, 2005. 24(2): p. 240-50.