UNIVERSITY OF OXFORD

BIOCHEMISTRY – 2013/2014

Research Topics and Supervisors willing to supervise Chemistry Part II students.

Professor J. P. Armitage (Biochemistry Department)
judith.armitage@bioch.ox.ac.uk
(1) Bacterial sensory pathways, their lack of cross-talk and engineering synthetic pathways. (2) The proton driven flagellar rotary motor. Techniques: in vitro and in vivo measurements of protein: protein interaction, Biacore, FRET, fluorescence microscopy, phosphotransfer kinetics, MS, biophysics etc combined with bioinformatics, mathematical and MD modelling, molecular genetics, and structural biology.
Porter, SL, Wadhams, GH and Armitage (2011) Signal processing in complex chemotaxis pathways Nature Revs Microbiol 9:153-65
Bell, CH, Porter, SL, Strawson, A, Stuart, DI & Armitage, JP (2010) Using structural information to change the phosphotransfer specificity of a Two-Component chemotaxis signalling complex PLoS Biology 8(2): e1000306
Delalez, N, Leake, MJ, Wadhams, GH, Berry, RM and Armitage, JP (2010) Dynamics of protein turnover in the functioning rotor of the bacterial flagellar motor PNAS 107:11347-51

Prof. B. C. Berks (Biochemistry Department)
http://www.bioch.ox.ac.uk/aspsite/research/brochure/Berks/
(1) Mechanism of an unusual protein transport system. (2) Redox proteins involved in the metabolism of sulfur compounds and of the greenhouse gas nitrous oxide. Techniques: protein chemistry; recombinant DNA technology and protein expression; structural biology; single molecule fluorescence; membrane proteins; bioinorganic chemistry.
Berks, B.C. et al. (2005) Protein targeting by the twin-arginine (Tat) translocation pathway (review). Curr.Opin.Microbiol. 8: 174-181.
Tarry, M.J., Schäfer, E., Chen, S., Buchanan, G., Greene, N.P., Lea, S.M., Palmer, T., Saibil, H.R., and Berks, B.C. (2009) Structural analysis of substrate binding by the TatBC component of the twin-arginine protein transport system. Proc.Natl.Acad.Sci.USA 106: 13284-13289.
White, G.F., Schermann, S.M., Bradley, J., Roberts, A., Greene, N.P., Berks, B.C., and Thomson, A.J. (2010) Subunit organisation in the TatA complex of the twin arginine protein translocase: a site-directed EPR spin labelling study. J.Biol.Chem. 285: 2294-2301.

Professor S. J. Ferguson (Biochemistry Department)
stuart.ferguson@bioch.ox.ac.uk
We use a multidisciplinary approach to study electron transport reactions. This includes properties and structures of novel enzymes and systems that reduce inorganic species e.g. nitrate, and nitrite, as well as studies of the assembly of proteins possessing cofactors containing Fe.
Molecular hijacking of siroheme for the synthesis of heme and d1 heme. Bali S, 7 others and Ferguson SJ (2011) Proceedings of the National Academy of Sciences in press
C-type cytochrome formation: Chemical and biological enigmas Stevens JM, Daltrop O, Allan JWA & Ferguson SJ (2004) Accounts of chemical Research 37, 999-1007
Nature Structural Biol. 2, 975 -982, Williams et al (1997) Nature 389, 406-412.

Dr Mark Howarth (Biochemistry Department)
mark.howarth@bioch.ox.ac.uk, http://users.ox.ac.uk/~bioc0756/MyWebs/activesite/index.htm
Bionanotechnology against cancer: new chemical and biological approaches to cancer diagnosis and imaging.
Particular projects include chemical modification of antibodies so that they form covalent bonds to protein targets, to reduce the detection limit of tumour markers; also adapting auto-catalyzed amide bond formation from a pathogenic bacterium to make a “protein superglue”. Techniques that may be used: chemical modification of proteins, organic synthesis, cell culture, single-molecule fluorescent microscopy, mass spectrometry, DNA manipulation (PCR, cloning, mutagenesis), protein structure determination by crystallography or NMR.
References:
Spontaneous Intermolecular Amide Bond Formation between Side Chains for Irreversible Peptide Targeting. Zakeri B & Howarth M. JACS 2010 Apr 7;132(13):4526-7.
Electrophilic affibodies forming covalent bonds to protein targets. Holm L, Moody P, Howarth M. J. Biol. Chem. 2009 Nov;284(47):32906-13.

Dr. Sylvia McLain (Biochemistry Department)
sylvia.mclain@bioch.ox.ac.uk; http://www.bioch.ox.ac.uk/research/mclain
Structure and dynamics of biomolecules- peptides and membrane components - on the atomic scale using a combination of experimental and computational techniques. Experimental techniques include a variety of neutron scattering techniques (performed at the ILL (Grenoble, France) and the ISIS Facility (STFC, UK)) as well as high-resolution NMR. Using these techniques, which are novel to biophysical applications, we aim to discover of the interplay between atoms and molecules and how this relates to complex biological phenomenon such as drug-delivery, protein folding and association in solution, the physical mileu where most of these interactions take place in nature.
Foglia, F., Lawrence, M.J., Lorenz, C.D. and McLain, S.E. (2010) On the hydration of the phosphocholine headgroup in aqueous solution. J. Chem. Phys. 133, 145103.
McLain, S.E., Soper, A.K., Diadone, I., Smith, J.C. and Watts, A.(2008) Charged based interactions between peptides observed as a dominant force for clustering in solution. Angew. Chem., Int. Ed., 47, 9059-9062.
McLain, S.E., Soper, A.K., Terry, A.E. and Watts, A.(2007) Structure and hydration of L-proline in aqueous solutions. J. Phys. Chem. B, 111, 4568-4580.
Fernandez-Alonso, F., McLain, S.E., Taylor, J.W., Bermejo, F.J., Bustinduy, I., Ruiz-Martin, M.D. and Turner, J.F.C. (2007) Correlated atomic motions in liquid deuterium flouride studied by coherent quasi-elastic neutron scattering. J. Chem. Phys. 126, 234509.
Hulme, E.C., Soper, A.K., McLain, S.E. and Finney, J.L. (2006) The hydration of the neurotransmitter acetylcholine in aqueous solution. Biophysical J. , 91, 2371-230.

Dr. Christina Redfield (Biochemistry Department)
christina.redfield@bioch.ox.ac.uk
Studies of protein structure, function, folding and dynamics using nuclear magnetic resonances spectroscopy.
Mavridou, D.A.I, Stevens, J.M., Ferguson, S.J. and Redfield, C. (2007) Active-site properties of the oxidized and reduced C-terminal domain of DsbD obtained by NMR spectroscopy. J. Mol. Biol. 370, 643-658.
Davis, J.A., Handford, P.A. and Redfield, C. (2007) The N1317H substitution associated with Leber congenital amaurosis results in impaired interdomain packing in human CRB1 EGF domains. J. BiolChem. 282, 28807-28814.

Professor M. S. P. Sansom (Structural Bioinformatics and Computational Biochemistry Unit, Biochemistry Dept.) mark.sansom@bioch.ox.ac.uk website http://sbcb.bioch.ox.ac.uk
My group is interested in using computational methods to explore the relationship between structure and function in membrane proteins. This is important, as membrane proteins account for ~25% of all genes, and play key roles in the physiology of cells. Indeed, membrane proteins are targets for ~50% of drugs, and mutations in membrane proteins may result in diseases ranging from diabetes to cystic fibrosis. Computer simulations allow membrane proteins to 'come alive' - that is, we can simulate the motions of membrane proteins and use this to explore the relationship between (static) structure and dynamic function. This is relevant to a number of areas ranging from biomedicine to nanotechnology.
Fowler, P.F., Tai, K. and Sansom, M.S.P. (2008) The selectivity of K+ ion channels: testing the hypotheses Biophys. J. 95: 5062-5072
Psachoulia, E., Fowler, P.F., Bond, P.J., and Sansom, M.S.P. (2008) Helix-helix interactions in membrane proteins: coarse grained simulations of glycophorin helix dimerization. Biochem. 47:10503-105012
Wallace, E.J. and Sansom, M.S.P. (2008) Blocking of carbon nanotube based nanoinjectors by lipids: a simulation study. Nano Letters. 8: 2751-2756
Scott, K.A., Bond, P.J., Ivetac, A., Chetwynd, A.P., Khalid, S., and Sansom, M.S.P. (2008) Coarse-grained MD simulations of membrane protein/bilayer self assembly. Structure 16:621-630

Dr Ioannis Vakonakis
<ioannis.vakonakis@bioch.ox.ac.uk>
Structural studies of pathogenic proteins in malaria cytoadherence.
1)Rasti, N., M. Wahlgren, and Q. Chen, Molecular aspects of malaria
pathogenesis. FEMS Immunol Med Microbiol, 2004. 41(1): p. 9-26.
2) Kraemer, S.M. and J.D. Smith, A family affair: var genes, PfEMP1
binding, and malaria disease. Curr Opin Microbiol, 2006. 9(4):
p.374-80.

Professor A. Watts (Biochemistry Department)
anthony.watts@bioch.ox.ac.uk; http://www.bioch.ox.ac.uk/~awatts/ Physical biochemistry of biomembranes. Most biophysical methods are being used, including solid-state NMR, spin-label electron spin resonance (DEER), electron microscopy, flourescence and calorimetry. For some of this work, we also develop new bio-organic synthetic methods for producing isotopically-labelled biomolecules, including lipids and proteins. An underlying theme is to describing the structure and dynamics of drugs and their targets to understand their mode of action, with G-protein coupled receptors being our main focus.
Judge, P. J. and Watts, A. (2011) Recent contributions from solid-state NMR to the understanding of membrane protein structure and function. Current Opinions in Chemical Biology, 15;690
Higman, V. A., Varga, K., Aslimovska, L., Judge, P.J., Sperling, L.J., Rienstra, C.M. and Watts A. (2011) The Conformation of Bacteriorhodopsin Loops in Purple Membranes Resolved by Solid-State MAS NMR Spectroscopy, Angew. Chem. Int. Ed. 2011, 50:1 – 5
Harding, P.J., Attrill, H.A., Boehringer, J., Ross, S., Wadhams, G.H., Smith, E., Armitage, J.P. and Watts, A. (2009) Constitutive dimerisation of the GPCR, neurotensin receptor 1, reconstituted into phospholipid bilayers. Biophys. J., 96, 964-973.
Williamson, P.T.F., Verhoeven, A., Miller, K.W., Meier, B.H. and Watts, A. (2007) The conformation of acetylcholine at its target site in the membrane-embedded nicotinic acetylcholine receptor. Proc. Nat. Acad. Sci. USA, 104, 18031-18036.
Watts, A. (2005) Solid state NMR in drug design and discovery for membrane embedded targets. Nature Reviews Drug Discovery, 4, 555-568.