Research groups

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Research

Protein Design and its Application in Bionanotechnology and Synthetic Biology

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: 

• We use bioinformatics methods to garner sequence-to-structure relationships from protein sequence and structural databases.
• 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).
• 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 (CD, FT-IR, NMR) and microscopy (EM, AFM and light microscopy).
• Finally, we explore potential applications of some the engineered and designed proteins in the burgeoning area of bionanotechnology. For instance, we are making self-assembled structures to act as substitutes for the extracellular matrix to foster specific cell growth for applications in tissue engineering, and we are developing peptide-based conformational switches as potential components of biosensors.

Merge sequence for a designed switch between a trimeric coiled coil (blue) and a zinc-finger structure (red)

We are interested in the folding and assembling of a number of protein-folding motifs, including zinc fingers and beta-structured proteins. However, our recent interest has focused the coiled-coil motif.

Coiled coils are protein-folding motifs that direct and cement a wide variety of protein-protein interaction throughout biology. They comprise two or more alpha-helices that wrap around one another to form helical ropes. Despite their apparent simplicity, these structures are ubiquitous and account for between 5-10% of all coding DNA sequence.

The bioinformatics challenge is to decipher rules within coiled-coil sequences that determine the different structures that are possible, and discriminate between different coiled-coil partners. It is these motifs and, more importantly, the sequence-to-structure rules that underlie them that the group examines and uses in de novo design.

Group

Emily Baker (with Charl Faul), Gail Bartlett, Marc Bruning, Berti Chi (with Paula Booth), Orhan Ertughrul, Jordan Fletcher (with Paula Booth), Leyla Hussein (with Leo Brady), Nazia Mehrban, Franziska Mende, John Simms (with Paula Booth), and Drew Thomson.

Recent publications

NR Zaccai, B Chi, AR Thomson, AL Boyle, GJ Bartlett, M Bruning, N Linden, RB Sessions, PJ Booth, RL Brady, DN Woolfson. (2011) A de novo peptide hexamer with a mutable channel. Nature Chemical Biology. 7: 935-941.

A Yoshizumi, JM Fletcher, Z Yu, A Persikov, GJ Bartlett, AL Boyle, TL Vincent, DN Woolfson, B Brodsky. (2011) Designed coiled coils promote folding of a recombinant bacterial collagen. Journal of Biological Chemistry. 286: 1715-1720.

GJ Bartlett, A Choudhary, RT Raines, DN Woolfson. (2010) n-->pi* interactions in proteins. Nature Chemical Biology. 6: 567-568.

EF Banwell, ES Abelardo, DJ Adams, MA Birchall, A Corrigan, AM Donald, M Kirkland, LC Serpell, MF Butler, DN Woolfson. (2009) Rational design and application of responsive alpha-helical peptide hydrogels. Nature Materials. 8: 596-600.

View all publications listed on the University of Bristol's publication database