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Biography
2018 Elected Fellow of the Royal Society of Chemistry
2015 Elected Fellow of the Royal Society of Biology
2012-2019: 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 Summary
Expertise in Analytical Ultracentrifugation, small angle X-ray scattering, small angle neutron scattering, isothermal titration calorimetry, protein expression and characterization. Also experience of protein crystallography, cryo-EM and NMR.
Research Summary
Scott Group
My research is based currently at the Research Complex at Harwell (www.rc-harwell.ac.uk) where I lead the Biophysical Methods Group. I am also a Senior Molecular Biology and Neutron Fellow (ISIS/STFC).
Current Group Members
Ryan Lithgo (BBSRC/Diamond), Emma Cowan (MRC IMPACT DTP),
Overview
We develop and use a variety of biophysical methods to characterise the interactions of biological macromolecules in solution and in the cell. These include proteins (soluble and membrane bound), protein/DNA complexes and nanoparticles. We have expertise in analytical ultracentrifugation, calorimetry, structural methods and various spectroscopies. We collaborate widely both nationally and internationally, and are actively involved in the University Nottingham BBSRC DTP and the MRC IMPACT DTP, with students from both schemes placed in our group.
Projects include:
1) Using neutrons to investigate biological macromolecules. We have chiefly used small angle neutron scattering to investigate the architecture of protein/DNA and membrane protein interactions. We are also developing methods in collaboration with the ISIS neutron source to probe macromolecules at very wide angles (1 > Q >100 A-1) using the NIMROD diffractometer. These reveal information about how the solvent interacts with proteins, and how small molecules alter the structure of the solvent. We have also initiated a program of investigation using muons to probe protein structure in both powders and solution, again in collaboration with ISIS scientists. This work is supported within the group by the STFC and through Wellcome/RCUK through our collaborators.
Publications:
a) Edwards MJ, White GF, Lockwood CW, Lawes M, Martel A, Harris G, Scott DJ,Richardson D, Butt JN, Clarke TA. Structural model of a porin-cytochrome electron conduit from the outer membrane of a metal reducing bacterium suggests electron transfer via periplasmic redox partners. J Biol Chem. 2018 Apr 10. pii:jbc.RA118.001850. doi: 10.1074/jbc.RA118.001850.
b) Hyde, E.I., Callow, P., Rajasekar, K.V., Timmins, P., Patel, T.R., Siligardi, G., Hussain, R., White, S.A., Thomas, C.M. & Scott D.J. (2016). Intrinsic disorder in the partitioning protein KorB persists after co-operative complex formation. Biochem J. 474 3121-3135.
c) Green, M., Hatter, L., Brookes, E., Soultanas, P. & Scott, D.J. (2016). Single-stranded DNA Stimulates Compaction of the C-Terminal Domain of SSB Signifying a Novel Mechanism of Action. J.Mol.Biol. 428 357-364
2) Bacterial silver resistance: As the efficacy of antibiotics declines, the interest in alternative small molecule strategies for combatting AMR have come to the fore. One strategy that has been actively pursued is the use of silver ions, Ag(I), which have have a higher toxicity to bacteria than mercury, but have little effect on humans. As such, silver compounds have been used in an unregulated manner in a variety of applications from personal care products, washing machines, medical devices and water sanitation. Not unsurprisingly, given its ubiquity, bacterial silver resistance in on the rise. We have cloned and expressed all of the sil genes from the silver resistant plasmid pMG101 with a view to characterising them structurally and functionally.
Publications:
(a) Asiani, K.R., Williams, H., Bird, L., Jenner, M., Searle, M.S., Hobman, J.L., Scott, D.J. and Soultanas, P. (2016). Antimicrobial resistance to silver encoded by the sil operon involves Ag+ binding to SilE an intrinsically disordered periplasmic 'molecular sponge'. Mol Microbiol. 101(5) 731-42.
3) Ube3A and its interactions: We are currently characterising the structure of the E3 ubiquitin ligase Ube3A, also known as E6AP (HPV E6 accessory protein) using protein crystallography and electron microscopy. This is an MRC funded project in collaboration with Prof. Rob Layfield (Nottingham), Dr. Steve Carr (Oxford/RCaH) and Dr. Katie Cunnea (eBIC/Diamond).
4) CCP-SAS: We are active participants in the Collaborative Computer Project for Small Angle Scattering which seeks to provide researchers with the means to use atomistic models of their relevant biomolecular systems for interpretation of small angle X-ray and neutron data. Our partners in this are University College London, ISIS Spallation Neutron and Muon Source, Diamond Light Source, the National Institute of Science and Technology, MA, USA and the Institute Laue Langevin, Grenoble France.
Publications:
(a) Perkins, S.J., Wright, D.W., Zhang, H., Brookes, E.H., Chen, J., Irving, T.C., Krueger, S., Barlow, D.J., Edler, K.J., Scott, D.J., Terrill, N.J., King, S.M., Butler, P.D. and Curtis, J.E. (2016) Atomistic modelling of scattering data in the Collaborative Computational Project for Small Angle Scattering (CCP-SAS). J Appl Crystallogr. 49 1861-1875
(b) Green, M., Hatter, L., Brookes, E., Soultanas, P. & Scott, D.J. (2016). Single-stranded DNA Stimulates Compaction of the C-Terminal Domain of SSB Signifying a Novel Mechanism of Action. J.Mol.Biol. 428 357-364
6) Development of analytical ultracentrifuge and small angle scattering theory
We have a long and ongoing program of developing theory for understanding biological macromolecules in dilute and concentrated solutions using small angle scattering. Much of this work has been done in collaboration with Prof. Don Winzor, University of Queensland, Australia, and Prof. Trushar Patel, University of Lethbridge, Canada. This has recently been complemented by the award of the 17ALERT BBSRC equipment grant for the latest OPTIMA multi-wavelength analytical ultracentrifuge.
Publications:
(a) Patel, T.R., Winzor, D.J. and Scott, D.J. (2017). Allowance for radial dilution in evaluating the concentration dependence of sedimentation coefficients for globular proteins. Eur.Biophys.J, In Press.
(b) Scott, D.J. (2016) Accounting for thermodynamic non-ideality in the Guinier region of small-angle scattering data of proteins. Biophys Rev. 8 441-444.
(c) Patel, T.R., Winzor, D.J. & Scott D.J. (2016). Analytical ultracentrifugation: A versatile tool for the characterisation of macromolecular complexes in solution. Methods 95 55-61
(d) Wills, P.R., Scott, D.J. & Winzor, D.J. (2015). The osmotic second virial coefficient for protein self-interaction: use and misuse to describe thermodynamic nonideality. Analytical Biochemistry 490 55-65
(e) Scott, D.J., Harding, S.E. & Winzor, D.J. (2015). Evaluation of diffusion coefficients by means of an approximate steady-state condition in sedimentation velocity distributions. Analytical Biochemistry 490 20-25
(f) Scott, D.J. and Winzor, D.J. (2015). Characterization of Intrinsically Disordered Proteins by Analytical Ultracentrifugation. Methods in Enzymology 562 225-239.
(g) Scott. D.J., Harding, S.E. and Winzor, D.J. (2014). The concentration dependence of protein diffusion coefficients. The Analyst J. 139, 6242-6248
Collaborative work.
We have always interested in new collaborations with groups and individuals both nationally and internationally. Please contact Dr. David Scott in the first instance to discuss any projects.
Collaborations with Doctoral training programs.
Currently we are an active participant of the Nottingham BBSRC DTP and MRC IMPACT DTP (Nottingham/Birmingham/Leicester) but through the RCaH can act as supervisors on any other collaborative DTP/CDT.Please contact Dr. David Scott in the first instance to discuss any projects.
Fellowship placement
The Research Complex at Harwell is a very well resourced, friendly and collaborative environment to place a fellowship. We already have visiting scientists within the group with their own fellowships, but will always happy to discuss placements or sponsorships of fellowships. Please contact Dr. David Scott in the first instance to discuss any projects.
Destinations of Former Group Members
Of the 4 PDRA's I have directly supervised, all have gone onto academic jobs: 1 RIKEN senior scientist, 1 Professor (Nottingham), 1 senior lecturer (Loughborough) and 1 lecturer (Kings College London), with the other 4 PDRA's I have co-supervised going on to various positions in industry, teaching and academia. Of the 24 PhD students who have graduated from my lab so far, the career destinations include academia, industry, finance and teaching. I take the supervision of PhD students and the training of PDRA's very seriously and work hard to find them employment at the end of their time in the group: I have also acted as a long term referee for their subsequent career stages. If you are interested in finding out more about working and studying in the Scott Group, please email Dr. David Scott.
Selected Publications
HYDE EI, CALLOW P, RAJASEKAR KV, TIMMINS P, PATEL TR, SILIGARDI G, HUSSAIN R, WHITE SA, THOMAS CM and SCOTT DJ, 2017. Intrinsic disorder in the partitioning protein KorB persists after co-operative complex formation with operator DNA and KorA. The Biochemical journal. 474(18), 3121-3135 GREEN, M., HATTER, L., BROOKES, E., SOULTANAS, P. and SCOTT, D.J., 2016. Defining the Intrinsically Disordered C-terminal Domain of SSB Reveals DNA-mediated Compaction Journal of Molecular Biology. 428, 357-364 ASIANI, K.R., WILLIAMS, H., BIRD, L., JENNER, M., SEARLE, M.S., HOBMAN, J.L., SCOTT, D.J. and SOULTANAS, P., 2016. SilE is an intrinsically disordered periplasmic ‘molecular sponge’ involved in bacterial silver resistance Molecular Microbiology. 101(5), 731-742