Professor Dek Woolfson

Summary

The primary basic research interests of the group are: (A) the informational aspect of the protein-folding problem; that is, how does the sequence of a protein determine its active, three-dimensional structure or fold?  And (B), how can we use this information to design completely new proteins from scratch?  In addition, we design proteins for applications in synthetic biology and medicine.

We tackle these problems using the following multi-disciplinary approach:

1. We use bioinformatics to garner sequence-to-structure relationships from protein sequence and structural databases.
   
   
2. We test the relationships ("rules for protein folding") that we find in two ways: (a) through ab initio protein-structure prediction; and (b) via rational protein design, where we engineer natural protein structures, or design new ones completely from scratch (so-called de novo design).
   
   
3. We then test our engineered and design proteins experimentally using biophysical methods. The peptides and proteins are made either by peptide synthesis, or via recombinant DNA methods and the expression of synthetic genes. The products and then characterised using methods including: solution-phase biophysics (CD, FT-IR and fluorescence spectroscopy, AUC and ITC); high-resolution structural biology (NMR spectroscopy and X-ray crystallography); and microscopy (EM, AFM and light microscopy).
   
   
4. Finally, we explore potential applications of some the engineered and designed proteins in the burgeoning fields of bionanotechnology and synthetic biology.

Professor Woolfson is a supervisor in the EPSRC Centre for Doctoral Training in Chemical Synthesis

Biography

Prof Dek Woolfson took his first degree in Chemistry at the University of Oxford in 1987.  He then did a PhD at the University of Cambridge followed by post-doctoral research at University College London and the University of California, Berkeley.  After 10 years as Lecturer through to Professor of Biochemistry at the University of Sussex, he moved to the University of Bristol in 2005 to take up a joint chair in Chemistry and Biochemistry.  His research has always been at the interface between chemistry and biology, applying chemical methods and principles to understand biological phenomena.  Specifically, his group is interested in the challenge of rational protein design, how this can be applied in synthetic biology and biotechnology, and with a particular emphasis on making completely new protein structures and functions, and also biomaterials for applications in biotechnology, cell biology and medicine.  Prof Woolfson is Director of BrisSynBio, a BBSRC/EPSRC-funded Synthetic Biology Research Centre.

Teaching

Prof Woolfson teaches in the Schools of Chemistry and Biochemistry, and on subjects in and around biological chemistry and physical biochemistry.  Specifically, he delivers lecture coures on protein structure, folding, design and assembly; and on chemical and synthetic biology.

Keywords

• bionanotechnology
• protein assembly
• protein design
• protein folding
• synthetic biology

Expertise

The primary basic research interest of the group is the informational aspect of the protein-folding problem; that is, how does the sequence of a protein determine its active, three-dimensional structure or fold? We tackle this problem using the following multi-disciplinary approach: 1. We use bioinformatics methods to garner sequence-to-structure relationships from protein sequence and structural databases. 2. We test the rules that we find using protein design, either through engineering natural protein structures, or by designing new sequences and structures completely from scratch (so called de novo design). 3. We then test our engineered and design proteins experimentally using biophysical methods. We make our designed and engineered peptides and proteins either by peptide synthesis or molecular biology methods. The products and then characterised using methods including spectroscopy and microscopy. 4. Finally, we explore potential applications of some the engineered and designed proteins in the burgeoning area of bionanotechnology.

Memberships

Organisations

School of Chemistry

Other sites

• Biochemistry
• Chemistry

Links

• Woolfson Group Research Pages

Selected publications

• Fletcher, JM, Harniman, RL, Barnes, FRH, Boyle, AL, Collins, AM, Mantell, J, Sharp, TH, Antognozzi, M, Booth, PJ, Linden, N, Miles, MJ, Sessions, RB, Verkade, P & Woolfson, DN, 2013, ‘Self-assembling cages from coiled-coil peptide modules’. Science, vol 340., pp. 595-599
• Thomson, AR, Wood, CW, Burton, AJ, Bartlett, GJ, Sessions, RB, Brady, RL & Woolfson, DN, 2014, ‘Computational design of water-soluble α-helical barrels’. Science, vol 346., pp. 485-488

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Recent publications

• Shoemark, DK, Ibarra, AA, Ross, JF, Beesley, JL, Bray, HE, Mosayebi, M, Linden, N, Liverpool, TB, McIntosh-Smith, SN, Woolfson, DN & Sessions, RB, 2019, ‘The dynamical interplay between a megadalton peptide nanocage and solutes probed by microsecond atomistic MD; Implications for design’. Physical Chemistry Chemical Physics, vol 21., pp. 137-147
• Jin, J, Baker, E, Wood, C, Bath, J, Woolfson, D & Tuberfield, A, 2019, ‘Peptide Assembly Directed and Quantified Using Megadalton DNA Nanostructures’. ACS Nano.
• Beesley, J & Woolfson, D, 2019, ‘The de novo design of α-helical peptides for supramolecular self-assembly’. Current Opinions in Biotechnology, vol 58., pp. 175-182
• Dawson, W, Rhys, G & Woolfson, D, 2019, ‘Towards functional de novo designed proteins’. Current Opinion in Chemical Biology, vol 52., pp. 102-111
• Goff, KP, Nicol, D, Williams, C, Crump, M, Zieleniewski, F, Samphire, J, Baker, E & Woolfson, D, 2019, ‘Stabilizing and Understanding a Miniprotein by Rational Redesign’. Biochemistry, vol 58., pp. 3060-3064
• Ibarra, AA, Bartlett, GJ, Hegedüs, Z, Dutt, S, Hobor, F, Horner, KA, Hetherington, K, Spence, K, Nelson, A, Edwards, TA, Woolfson, DN, Sessions, RB & Wilson, AJ, 2019, ‘Predicting and Experimentally Validating Hot-spot Residues at Protein-Protein Interfaces’. ACS Chemical Biology.
• Smith, A, Thomas, F, Shoemark, D, Woolfson, D & Savery, N, 2019, ‘Guiding Biomolecular Interactions in Cells Using de Novo Protein - Protein Interfaces’. ACS Synthetic Biology, vol 8., pp. 1284-1293
• Rhys, GG, Wood, CW, Beesley, JL, Zaccai, NR, Burton, AJ, Brady, RL, Thomson, AR & Woolfson, DN, 2019, ‘Navigating the Structural Landscape of De Novo α-Helical Bundles’. Journal of the American Chemical Society, vol 141., pp. 8787-8797

View complete publications list in the University of Bristol publications system