2015 Elected Fellow of the Royal Society of Biology
2012-present: STFC Senior Molecular Biology and Neutron Fellow
2012-present: Group Leader in Biophysical Methods in the Research Complex at Harwell.
2011-present: Associate Professor and Reader in Physical Biochemistry.
2009-2011: Associate Professor in Physical Biochemistry, University of Nottingham and Deputy Director of the National Centre for Macromolecular Hydrodynamics, University of Nottingham. 2003-2009: Lecturer in Physical Biochemistry. University of Nottingham. 2001-2003: Post-doctoral research associate. Department of Biochemistry, University of Bristol. I worked for Prof. SteveHalford on a Wellcome funded programme grant to study the mechanism of Type II restriction enzymes that require one and two DNA binding sites. 2000-2001: Post-doctoral research assistant, Oxford Centre for Molecular Sciences, University of Oxford/YSBL, Department of Chemistry, University of York. For this year I worked 50 % of the time in the laboratory of Prof. Carol Robinson at Oxfordanalysing non-covalent macromolecular complex formation using nanospray mass spectrometry. The rest of the time I continued to work in the YSBL. 1999-2000: Post-doctoral research assistant, York Structural Biology Laboratory, Departments of Chemistry and of Biology, University of York. BBSRC funded position in the YSBL. I was involved in developing biophysical techniques such as analytical ultracentrifugation, isothermal titration calorimetry and small angle scattering. 1996-1999: Post-doctoral research assistant, Department of Biology, University of York. BBSRC 3 year project grant working for Dr. Jim Hoggett on interactions of sigmaN with E. coli RNA polymerase using novel tryptophan analogues.
Graduate and Undergraduate Studies
1992-1996: Postgraduate, Department of Biology, University of Leeds. PhD Thesis: "Kinetic analysis of bacteriophage MS2 self-assembly", supervised by Prof. Peter Stockley.
1989-1992: Undergraduate, Department of Biochemistry and Molecular Biology, University of Leeds. BSc Molecular Biophysics
Expertise in Analytical Ultracentrifugation, small angle X-ray scattering, small angle neutron scattering, isothermal titration calorimetry, protein expression and characterisation. Also experience of protein crystallography, cro-EM and NMR.
D24BT8 Structural Biology; D224G1 Employavility modeule. I also teach into the Microbiology BSc, and supervise final year Microbiology students in their 3rd year lab based projects.
I am currently seconded two days a week to the Research Complex at Harwell (www.rc-harwell.ac.uk) where I am Group Leader in Biophysical Methods. I hold an appointment as the ISIS Senior Molecular… read more
RAJESKAR, K., MUNTAHA, S.T., TAME, J.R.H., KOMMAREDDY, S., MORRIS, G., WHARTON, C.M., THOMAS, C.M, WHITE, S.A, HYDE, E.I. and SCOTT, D.J., 2010. Order and disorder in the domain organisation of the plasmid partition protein KorB The Journal of Biological Chemistry. 285, 15440-15449
I am currently seconded two days a week to the Research Complex at Harwell (www.rc-harwell.ac.uk) where I am Group Leader in Biophysical Methods. I hold an appointment as the ISIS Senior Molecular Biology and Neutron Fellow, sponsored by the STFC.
The Scott Group: We work on a variety of biophysical and biological problems centred around how organisms deal with and process biological information. Current projects include: Olfaction, intrinsic disorder in proteins, transcriptions and aggregate structure and formation in pharmaceutical preparations and development of methodologies to cope with non-ideal highly concentrated solutions.
Biophysical Techniques used: Analytical ultracentrifugation, isothermal titration calorimetry, light scattering, small angle X-ray and neutron scattering and hydrodynamic modelling.
Other techniques: Standard molecular biology for isolation and overexpression of target genes. RT-PCR, receptor analysis, single gene knockouts. We also have over-expression systems for yeast, archaea and bacteria.
We are, or have been funded by BBSRC, MRC, The Wellcome Trust, STFC, EPSRC, UNESCO, Royal Society and the University of Nottingham.
My current research is based around using multiple biophysical techniques in order to elucidate structure/function relationships. I am keenly interested in employing techniques such as small angle scattering, hydrodynamic and structure determination to elucidate larger and more flexible systems. This has an obvious link with other techniques such as electron and atomic force microscopies, as well as protein crystallography, spectroscopy and NMR structural methods.
Silver resistance in bacteria
This project, in collaboration with the Oxford Protein Production Factory (www.oppf.ac.uk) is to structurally characterize proteins involved in silver resistance in bacteria. Silver is a powerful anti-microbial, and as such is used extensively in the environment to prevent microbial growth in applications as diverse as medical devices, brewing equipment, deodorants and hosiery. Inevitably, silver resistance has emerged, and is starting to pose a threat to human health. We have successfully cloned and overexpressed four of the proteins, SilE, SilR, SilS and SilP, the last of which is a membrane spanning protein we have at relatively high expression (c.a 2-4 mg/litre) for crystallization trials. Once these are characterized, we wish to functionally characterize the proteins, and then start to build a system level model of their interactions.
Hydrodynamic descriptions of flexible and intrinsically disordered protein molecules
I have for sometime been interested in analysing more complex and flexible macromolecules using hydrodynamic techniques. Flexibility is often intimately tied to function. The plasmid partition protein KorB is essential for the correct segregation of the low copy number, broad host range, RK2 plasmid, while also being an important regulator of transcription. KorB belongs to the ParB family of proteins and partitioning in RK2 has been much studied as a simplified model of bacterial chromosome segregation. Structural information on full-length ParB proteins is limited, mainly due to the inability to grow crystals suitable for diffraction studies. Using a combination of biophysical techniques to study KorB and a set of its deletion mutants, it can be shown that there is significant intrinsic disorder in KorB, which means that it adopts a multiplicity of conformations in solution.The data is consistent with predictions based on the amino acid sequence that the N-terminal region and also the region between the central DNA-binding domain and the C-terminal dimerisation domain are intrinsically disordered. Using SAXS and the known domain structures to model an ensemble of solution conformations for KorB, and selected deletion mutants. The full length wild type protein shows the full diversity of conformations, the conformational diversity decreases for (NΔ150)KorB, (lacking the N-terminal 150 residues) suggesting that the linker is somewhat compact, and is smallest for (CΔ105)KorB, a monomer with only one flexible region. The conformational range of KorB is likely to be biologically important in DNA partitioning and for its binding to diverse partner proteins Using SANS it has been possible to determine the difference in conformations adopted when an activator protein, KorA binds. This work is now being prepared for publication and is part of ongoing work at D22 of the ILL.
References: Rajeskar, K.V., Muntaha, S.T., Tame, J.R.H., Wharton, C.M., Thomas, C.M., White, S.A., Hyde, E.I. and Scott, D.J. (2010). Order and disorder in the domain organisation of the plasmid partition protein KorB. J. Biol. Chem. Accepted.