Undergraduate Course

Department of Chemistry University of Oxford

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


Prof. Mark Howarth (Biochemistry Department)
mark.howarth@bioch.ox.ac.uk , http://www.bioch.ox.ac.uk/howarth
Bionanotechnology for intelligent cell activation and vaccination.
Particular projects include solid-phase synthesis of polypeptide teams, for controlled triggering of cancer cell death or magnetic cancer cell capture for early diagnosis; also adapting auto-catalysed amide bond formation from bacteria to make “protein superglues” to engineer viral particles for new kinds of vaccine. Techniques that may be used: chemical modification of proteins, cell culture, fluorescence microscopy, mass spectrometry, DNA manipulation (PCR, cloning, mutagenesis), protein design and evolution, X-ray crystallography. 
References:
Secrets of a covalent interaction for biomaterials and biotechnology: SpyTag and SpyCatcher. Reddington SC, Howarth M. Curr Opin Chem Biol 2015 Oct 27;29:94-99.
Plug-and-Display: decoration of Virus-Like Particles via isopeptide bonds for modular immunization. Brune KD, Leneghan D, Brian IJ, Ishizuka AS, Bachmann MF, Draper SJ, Biswas S, Howarth M. Sci Rep 2016 Jan 19;6:19234.

Prof. Christina Redfield (Biochemistry Department)
christina.redfield@bioch.ox.ac.uk
http://www.bioch.ox.ac.uk/aspsite/index.asp?pageid=596

High-field NMR (500-950 MHz) is used to study the structure, dynamics, interactions and folding of proteins in solution.
L.J. Smith, A. Bowen, A. DiPaolo, A. Matagne and C. Redfield, The Dynamics of Lysozyme from Bacteriophage Lambda in Solution probed by NMR and MD simulations, ChemBioChem 14, 1780-1788 (2013).
D.A. Yadin, I.B. Robertson, J. McNaught-Davis, P. Evans, D. Stoddart, P.A. Handford, S.A. Jensen and C. Redfield, Structure of the fibrillin-1 N-terminal domains suggests heparan sulphate regulates the early stages of microfibril assembly, Structure 21, 1743-1756 (2013). D.A.I. Mavridou, E. Saridakis, P. Kritsiligkou, E.C. Mozley, S.J. Ferguson and C. Redfield, An extended active-site motif controls the reactivity of the thioredoxin fold. J. Biol. Chem. 289, 8681-8696 (2014).
P.C. Weisshuhn, D. Sheppard, P. Taylor, P. Whiteman, S.M. Lea, P.A. Handford and C. Redfield, Non-linear and flexible regions of the human Notch-1 extracellular domain revealed by high-resolution structural studies, Structure, 24, 555-566 (2016).

Prof. 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

Prof. Ioannis Vakonakis (Structural Biology and Biophysics, Biochemistry Department)
ioannis.vakonakis@bioch.ox.ac.ukhttp://www.bioch.ox.ac.uk/vakonakislab/
My group seeks to understand at the amino-acid level how large assemblies of proteins organise in cells. We target a broad range of systems from enzymatic complexes, such as chaperones and phosphatases, to disease-causing cell structures in malaria and to full-fledged cell organelles, such as centrosomes. Understanding cellular assemblies at high-resolution is prerequisite for developing successful interventions, such as small molecule inhibitors, to tackle human disease. We use a broad spectrum of biophysical and structural biology techniques ranging from X-ray crystallography to microscopy, NMR and biochemical assays.
Rogala, K.B., Dynes, N.J., Hatzopoulos, G.N., Yan, J., Pong, S.K., Robinson, C.V., Deane, C.M., Gönczy, P., Vakonakis, I. (2015) The Caenorhabditis elegans protein SAS-5 forms large oligomeric assemblies critical for centriole formation. eLife 4, e07410.
Oberli, A., Slater, L.M., Cutts, E., Brand, F., Mundwiler-Pachlatko, E., Rusch, S., Masik, M.F.G., Erat, M.C., Beck, H.P., Vakonakis, I. (2014) A Plasmodium falciparum PHIST protein binds the virulence factor PfEMP1 and co-migrates to knobs on the host cell surface. FASEB J. 28, 4420-33.
Kitagawa, D., Vakonakis, I., Olieric, N., Hilbert, M., Keller, D., Olieric, V., Bortfeld, M., Erat, M.C., Flückiger, I., Gönczy, P., Steinmetz, M.O. (2011) Structural Basis of the 9-Fold Symmetry of Centrioles. Cell. 144, 364-75.

Prof. 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. Additionally, we are designing peptides for use as antimicrobial agents to fight AMR.
• 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, et al., (2011) The Conformation of Bacteriorhodopsin Loops in Purple Membranes Resolved by Solid-State MAS NMR Spectroscopy, Angew. Chem. Int. Ed. 2011, 50:1 – 5
• Pyne et al., (2016) Engineering monolayer poration for rapid exfoliation of microbial membranes, Chemical Science, DOI: 10.1039/C6SC02925F
• Rakowska, et al., (2013) Nanoscale imaging reveals laterally expanding antimicrobial pores in lipid bilayers. Proc. Natl. Academ. Sci.(USA), 110, 8918-892