Study of Membrane Protein Complexes3d Models of Protein Complexes

BBSRC_PROJECTS_3.11.2010.DOCX1/130/11/201810:36:04

1. CORE RESEARCH AREAS CURRENTLY FUNDED BY THE BBSRC. These areas have attracted generous funds from the BBSRC. Candidates interested in doing a PhD in one or more of these areas are strongly encouraged to apply.
PI / Dr James Allen
URL /
Research area:
/ Assembly of cytochrome c in the African sleeping sickness parasite. The genome of the African sleeping sickness parasite Trypanosoma brucei reveals a typical mitochondrial respiratory chain but none of the known proteins for cytochrome c assembly. We are seeking to identify and characterize the proteins that do this job in trypanosomes.
Research methods:
/ Rotation: Microbiological culture (bacterial and eukaryotic); Protein purification; Bacterial molecular biology; Various protein chemistry methods; Mass spectrometry; Gel electrophoresis; Absorption spectroscopy; Bioinformatics/genome analysis; Enzymology; Immunoprecipitation. DPhil project: Advanced molecular biology (bacterial & eukaryotic – e.g. cloning and expression, constructing trypanosome gene knockouts, RNAi); Membrane protein expression, purification, etc.; Advanced enzymology (e.g. detailed characterization, inhibitor studies, etc.); Protein crystallography; Advanced spectroscopic methods.
PI / Professor Judith P. Armitage
URL /
Research area:
/ E.coli chemosensing is the best understood sensory system in biology, with transmembrane chemoreceptors regulating the activity of a histidine kinase which determines the phosphorylation state of the flagellar motor binding response regulator. However, in most other species sensing is more complex, with several pathways controlling behaviour. Research will centre on (a) identifying whether signalling pathways are linear or parallel and (b) the dynamics of the sensory proteins which are localised to specific regions of the bacterial cell.
Research methods:
/ All aspects of cloning, fluorescence microscopy, protein:protein interaction measurement (in vivo by FRET, in vitro by SPR and yeast two hybrid), bioinformatics, behavioural analysis.
PI / Professor Fraser Armstrong
URL /

Research area: / Biological oxidation and reduction. Mechanistic studies on long-range electron transfer and proton transfer in enzymes. Investigations of enzymes containing metal cofactors. Studies and exploitation of oxidases and hydrogenases, including oxidation and production of hydrogen by enzymes and the applications to ‘smart’ hydrogen and novel fuel cell technologies.
Research methods: / Many electrochemical techniques including ‘protein film volatmmetry’ and potential step kinetic methods. Rapid solution kinetics (stopped flow). Electron paramagnetic resonance (EPR). Anaerobic (glovebox techniques. Microbiology, molecular biology and protein chemistry.
PI / Professor Hagan Bayley
URL /

Research area: / Membrane protein folding, assembly and function; membrane protein engineering; rapid screening of membrane proteins; Bionanotechnology
Research methods:
/ Research methods: molecular genetics, protein chemistry, organic synthesis, biophysical measurements including single-channel recording
PI / Dr Ben Berks
URL /

Research area: / Mechanism of an unusual protein transport system; molecular basis of
bacterial sulfur oxidation; membrane protein structural biology
Research methods:
/ Protein chemistry (protein purification, antibody methodology, in vitro
transcription-translation, protein modification, enzymology, protein
biophysics); membrane biology; recombinant DNA methodology; structural biology (X-ray crystallography, single particle electron microscopy, high throughput expression methods, molecular dynamics); single cell and single molecule fluorescence methods.
PI / Professor Benjamin G. Davis
URL /


Research area: / Chemical Glycobiology, Biocatalysis and Mechanistic Enzymology, Protein and Glycoprotein Chemistry, Inhibitor and Small-Molecule Probe Design, Antivirals, Chemical Genetics, Synthetic Methodology, Glycoimmunology, Drug Delivery, In Vivo imaging, Therapeutic Strategies, Biopharmaceuticals.
Research methods:
/ Mechanistic Enzymology, Synthetic Methodology, Inhibitor and Small-Molecule Probe Design, Sugar Chemistry, Asymmetric Small Molecule Chemistry, Peptide Synthesis, Molecular Biology, Protein Expression, Forced Evolution, Structural Biology, Mass Spectrometry, Novel Chemistry on Protein Surfaces, In Vivo Methods.
PI / Professor Stuart Ferguson
URL /

Research area:
/ Structure, function, molecular mechanism, biogenesis and assembly of bacterial respiratory proteins of the Nitrogen cycle.
Research methods: / Molecular and structural biology; spectroscopy and other biophysical methods; enzymology; protein biochemistry; recombinant protein expression, purification and characterisation
PI / Dr Mark Howarth
URL /

Research area / Bionanotechnology:
Discovery of new types of post-translational modifications involved in bacterial infection and cancer. Use of protein chemistry to design infinite affinity antibodies for imaging and diagnosis. Protein “superglue” and padlocks from pathogenic bacteria.
Research methods / Molecular and cellular biology, protein engineering and selection, fluorescence microscopy, X-ray crystallography, basic organic synthesis, mammalian cell culture, small-molecule probe design, mass spectrometry, proteomics, bioinformatics
PI
URL / Dr Nicholas Lakin

Research area:
/ Maintenance of genome integrity: The detection signalling and repair of DNA damage. Repair of DNA damage is critical to maintain genome integrity. As such, the cell has developed a DNA damage response (DDR) that detects and signals DNA damage to facilitate cell cycle arrest and DNA repair. Our research exploits mammalian cell culture and the genetic model organism Dictyosteliumto decipher how the DDR is regulated at the molecular level. Research areas include (i) Understanding how DNA damage is detected and signalled to initiate the DDR and (ii) how repair of DNA double strand breaks isregulated.
Research methods:
/ Recombinant DNA technology (gene cloning/manipulation), mammalian and Dictyosteliumcell culture, genetics/chemical genetics (gene disruption, siRNA, small molecule inhibitors of DNA repair), biochemistry (protein expression, purification and analysis), cell biology (microscopy and immunofluorescence).
PI / Dr Christina Redfield
URL /
Research area: / NMR methods for characterising partly folded and unfolded proteins
and study of ligand-binding protein systems
Research methods:
/ Protein NMR methods including double and triple resonance 2D and 3D NMR, 15N relaxation studies and residual dipolar couplings
PI / Professor Carol Robinson
URL /
Research area: /

Study of membrane protein complexes3D models of protein complexes

Research methods:
/ We are interested in all aspects of protein complexes and their properties in the gas phase of a mass spectrometer. Although not the traditional role of this analytical tool, recent developments enable mass spectrometry to probe large intact protein assemblies, providing knowledge of their stoichiometry, topology and interaction partners
PI / Professor Chris Schofield
URL /

Research area:
/ Molecular understanding of the mechanisms behind the hypoxic response (how cells counteract the effect so low oxygen, e.g. at altitude or in tumours), the biosynthesis of antibiotics, the structures and mechanisms of enzymes that catalyse synthetically impossible reactions, functional assignment and selective inhibition of human enzymes, regulating transcription by small molecules.
Research methods:
/ Molecular and cellular biology, protein purification and characterisation, proteomics (including MS based methodology and techniques for studying protein-protein interactions), structural biophysics, especially crystallography and MS, organic synthesis especially of enzyme inhibitors.
PI / Dr Mark Wallace
URL /

Research area:
/ Single-molecule detection of membrane proteins
(Bionanotechnology, Molecular Mechanisms of Biological Systems,
Physical Biochemistry)
Research methods:
/ Single-molecule fluorescence techniques; Laser spectroscopy;
Microscopy; Single-channel electrical recording; Protein expression,
purification, and chemical modification.
2. AdditionalResearch Areas for rotation projects and collaborative dphil projects. These areas may not currently supported by BBSRC research grants but fall within the remit of BBSRC, and therefore would provide interesting possibilities for collaborative projects in collaboration with the main areas above.
PI / Professor Harry L. Anderson
URL /

Research area: / Design, synthesis and testing of dyes for a wide range of applications, particularly using porphyrins and rotaxanes; drugs for two-photon excited photodynamic therapy; membrane-probes based on second harmonic generations; nonlinear optics; molecular recognition; supramolecular chemistry and chromophore engineering.
Research methods: / Organic synthesis; fluorescence spectroscopy; NMR; mass spectrometry; HPLC; tissue culture experiments.
PI / Dr Phil Biggin
URL /


Research area: / Ionotropic Glutamate Receptors, Nicotinic Acetylcholine Receptors, Neurotransmission, Anti-viral agents, Lipid-drug interactions, Drug-receptor binding, Conformational change in proteins
Research methods: / Structural Bioinformatics, Molecular Dynamics, Free Energy Calculations, Homology Modelling, Normal Mode Analysis.
PI / Professor Raymond Dwek with Dr Nicole Zitzmann
URL /
nicole.zitzmann @bioch.ox.ac.uk
Research area: / Development of antiviral therapeutics for Hepatitis C virus, Hepatitis B virus, and HIV. Biophysical and structural studies of the ion channels.
Antiviral drug discovery, ion channel inhibitors and sugar-based anti-HIV therapeutics
Research methods: / Molecular biology; cell culture; ion channel studies in black lipid membranes; structural and biophysical techniques including crystallography, NMR, circular dichroism, differential scanning calorimetry.
PI / Professor T.J. Donohoe
URL /

Research area: / Synthetic Methodology for Complex Molecules with Biological Activity
Research methods:
/ Synthetic organic chemistry: development of new methodologies for synthetic organic chemistry and asymmetric synthesis, and application to synthesis of biologically important natural products.
PI / Professor Jane Endicott
URL /
Research area: / Structural and biochemical characterisation of the Plasmodium falciparum protein kinase family.
Research methods:
/ Molecular biology, protein purification and characterisation, X-ray crystallography, principles in structure-aided inhibitor design,
biophysical techniques to characterise protein-protein interactions, to include SPR and ITC.
PI / Dr Antony Fairbanks
URL /

Research area:
/ Glycochemistry; carbohydrate based drug discovery e.g. anti-fungals and antibiotics; glycoprotein and glycopeptide chemistry
Research methods: / Synthetic methodology, sugar chemistry.
PI / Dr Elspeth Garman
URL /
Research area:
/ Structural BiologyMethodology, Crystallography. Macromolecular Crystallography. Methods development. Cryo-techniques and understanding of radiation damage. Metal identification in proteins. Structural studies on neuraminidases.
Research methods: / Crystallography, microPIXE.
PI / Professor Penny Handford
URL /
Research area:
/ Molecular Mechanisms of Biological Systems focussing on structural and functional consequences of Notch-ligand interactions; and intra- and inter-molecular interactionsof calcium-dependent extracellular matrix proteins
Research methods:
/ General molecular biology (DNA and protein analytical methods), specific expertise in vitro refolding of disulphide-rich proteins, measurement of weak, moderate and high affinity calcium binding sites in proteins, prokaryotic and eukaryotic protein expression, biophysical methods (NMR, crystallography, surface plasmon resonance)
PI / Professor Peter J. Hore
URL /

Research area:
/ Real-time kinetic NMR studies of protein folding
Structural studies of partially folded proteins using photo-CIDNP
Research methods:
/ High resolution NMR
Laser kinetics
Photo-CIDNP (Chemically Induced Dynamic Nuclear Polarization)
PI / Dr Petros Ligoxygakis
URL /

Research area:
/ Pathogen recognitionby theinnate immune system, using a genetically tractable organism (Drosophila melanogaster.) as a model system
Research methods:
/ Standard molecular biology (cloning, PCR, RNA work), protein biochemistry (expression, purification), bacterial cell wall chemistry (peptidoglycan purification, isolation of smaller fragments with HPLC), Drosophila genetics (mutagenesis, genetic transformation, crosses), study of the interaction between immune receptors and the bacterial cell wall using confocal microscopy.
PI / Professor Martin Noble
URL /
Research area: / Structural studies on regulatory proteins; Adhesive interactions, the cell cycle, and NAT enzymes
Research methods:
/ Protein X-ray crystallography and other biophysical methods; drug design; visualization/analysis; protein binding interactions
PI / Dr James Parker
URL /
Research area: / Research area: Structural and molecular biology of RNA silencing: RNA interference, microRNAs, piRNAs, Argonaute, Dicer, Slicer - fundamental biology and basic molecular mechanisms
Research methods:
/ Molecular biology, protein biochemistry, X-ray crystallography, biophysical methods (isothermal titration calorimetry, analytical ultracentrifugation)
PI / Dr Jason Schnell
URL /
Research area:
/ Structure, function, and inhibition studies of ion channels that are of high medical relevance. Structural analysis of ion channel systems by high-resolution solution NMR and other the tools of biophysics (e.g. fluorescence, and ultracentrifugation) and molecular biology in combination with functional assays (e.g. liposomal ion flux assays) to elucidate the molecular details of activity.
Research methods:
/ Molecular Biology, Protein Biochemistry, NMR spectroscopy,
Mass Spectrometry, Surface Plasmon Resonance, Calorimetry, Time-Resolved Spectroscopies, Structure-Based Drug Design, Combinatorial Library Screening.
PI / Dr Lorna Smith
URL /

Research area:
/ Experimental and theoretical methods to characterise partially folded and misfolded proteins. NMR studies of protein structure, dynamics and ligand binding.
Research methods:
/ Protein NMR Spectroscopy - 2D and 3D techniques
Theoretical molecular dynamics simulations.
PI / Dr Christiane R. Timmel
URL /

Research area:
/ Investigations of stable and transient radicals in chemical and biological systems, Electron Paramagnetic Resonance (EPR), Magnetic Field Effects (MFEs)
Research methods:
/ Continuous and pulsed Electron Paramagnetic Resonance,
Magnetically Affected Reaction Yields (MARY)
Oscillating Magnetic Field Effects (OMFE)
Reaction Yield Detected Magnetic Resonance (RYDMR)
Laser Flash Photolysis
PI / Dr George Wadhams
URL /

Research area:
/ Bacterial motility and chemotaxis, Synthetic biology, Biosensor design and construction. Molecular understanding of the processes governing signal amplification and gain in the bacterial chemotaxis system, synthesis of novel bacterial signalling pathways from existing modular biochemical components, development of rationally designed signalling pathways for use as biosensors.
Research methods:
/ Microbiology, molecular biology, protein purification, fluorescence microscopy (including TIRF).
PI / Professor Anthony Watts
URL /
Research area:
/ Ligand activation of GPCRs, Membrane protein expression, Membrane protein reconstitution, Solid state NMR of membrane receptors, Single molecule studies of membrane receptors, computational approaches to drug docking, multifrequency electron spin resonance of membrane proteins.
Research methods:
/ Membrane biochemistry and molecular biology, surface plasmon resonance, solid state NMR, computational simulations, multifrequency electron spin resonance, bioorganic chemistry for labelling biomolecules
PI / Dr L.-L Wong
URL /
Research area:
/ Biocatalysis, Redox Enzymes, Biosensors
Research methods:
/ Biological Chemistry