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Dafydd Jones

Professor Dafydd Jones

Professor

School of Biosciences

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Available for postgraduate supervision

Overview

Research overview

The main focus of the Jones group is the structural and functional plasticity of proteins. Our research involves the study and engineering of a variety of protein systems, with a focus on fluorescent proteins and antibiotic resistance systems. Much of the group's work lies at the interface between biology, chemistry and physics and has a basis in the protein side of synthetic biology whereby we construct new proteins components, new scaffolds and bionanohybrid systems. We have a particualr interest in introducing new chemistry into proteins throught the use of expanded genetic code approaches and interfacing proteins in a designed manner with nano-materials to generate for protein-gated nanodevices and biomolecular electronics. We have also developed several transposon-based methods for the directed evolution of proteins using non-homologous recombination. The groups uses a variety of approaches including computational design, rational protein engineering and directed evolution with structural biology, single molecule analysis, moleculart dynamics, biophysics and biochemical techniques used to investigate the properties of these novel proteins.

Resources

Here is a link to my PyMOL Tutorial <<<<<

News

Great collabration between Sébastien Côté (U of Montreal, Canada), Chang-Seuk Lee (Seoul Women's University, S Korea) and again with Matteo Palma (QMUL) on how we used computer simulations and modelling to predict how proteins will electrostatically gate carbon nanotube field effect transistors. The paper is published in Nature Communications

We have a new BBSRC TRT grant to work on developing new fluorescent protein tools to monitor protein complex formation. Great collaboration with colleagues Richard Clarkson, Georgina Menzies and Pete Watson

So you thought you know how glycosylation affects a protein? Our new paper in FEBS J with collaboraters Georgina Menzies , Stephen Wells, and Chris Pudney show that gylcans made the important commerical enzyme horse radish peroxidase more rigid - yes more rigid - and making it much more active and stable compared to its non-glycosylated form. A good blend of experiment and simulation were used to show how the structural affects and dynamics were manfested. 

We had a lot of interest in our recent paper in Advanced Functional Materials concerning the use of flourescent proteins to optically gate conductance of carbon nanotubes, including highlighted articles in Phys.org, AAS EurekAlert, Technology Networks amongst others. We essentially show that GFP can enable either optically gated transistor or memory function based on how we photochemically attach the protein to the CNT. All this enabled by genetically encoded phenyl azide chemistry. 

New paper published published in Open Biology using biochemistry, structural biology and molecular dynamics to understand cold adaption of an family IV esterase. We find that global and local dynamics are not the key drivers for cold activity but most likely solvent interactions and access to the active site. Excellent international collaboration with Nehad Noby at Alexandria University in Egypt together with Stephen Wells and Chris Pudney in Bath.

New paper published in Angewandte Chemie Int Ed combining synthetic biology with nanoscience about how conductance changes through a carbon nanotube by altering the local protein electrostatic surface within the Debye length. Critical was defining the protein-CNT interaction so we can control which electrostatic surface comes close to the CNT. We brought together  to  We applied this to detecting proteins involved in causing resistence to common antibiotics. Another wonderful collaboration with Matteo Palma at QMUL.

Highly competitive EPSRC New Horizons grant awarded for developing genetically encoded far red/IR probes for new bioimaging approaches. Excellent collaboration with Paola Borri, Wolfgang Langbein and Pete Watson.

Publication

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Articles

Book sections

Conferences

Research

The Jones group focus on understanding the molecular basis of protein plasticity in terms of structure, function and folding, and its application to the construction of new protein components and systems. The ultimate aim is to address one of the fundamental questions in biology: how amino acid sequence encodes the information for a protein to fold to its functional 3D structure. Our group collaborates chemists, structural biologists, computer modellers and physicists. Constructing new protein components means our work is closely aligned with the areas of synthetic biology and nanoscience/nanotechnology.

Protein structure, function, dynamics and engineering

The structure, function and folding of a range of proteins are investigated using biochemical, biophysical, structural biology and molecular dynamics. One of the main focuses of the group currently are fluorescent proteins, haem binding proteins and ß-lactam antimicrobial resistance systems. We also have an interest in various enzymes including the subtilisin serine proteases and cold-active esterases.

A full list of the structure determined by the group can be found here.

Construction of artificial protein scaffolds

The ability to design new proteins with activities not part of the natural repertoire is essential as part of the development of synthetic biology and bionanotechnology. As a general approach for creating tailored protein components with unique but useful properties, we couple the structures and hence functions of normally unrelated proteins or even non-protein materials so as to link the function. To achieve this, existing proteins will require radical redesign or even the creation of new scaffolds. However, natural proteins provide the inspiration and guidance during construction. One key aspect we aim for is synergy between different components so that one component “talks” to the other.

The group uses a variety of approaches to construct these new scaffold including: (1) domain insertion by directed evolution; (2) rational domain grafting; (3) linking proteins via click chemistry; (4) constructing bionanohybrids in which proteins are linked to secondary molecular systems such as DNA origami and nano-carbon.

We have recently successfully demonstrated designed interfacing of proteins to both the side-wall and end wall of nano-carbon systems using both light and click chemistry approaches. The two systems are functionally coupled due to the designed and intimate interface between the two molecular systems.

Single molecule studies of electron and energy transfer proteins

Electron and energy transfer plays a vital role in biology being pivotal to processes such as photosynthesis, respiration and enzyme catalysis. Such proteins essentially work at the single molecule but most approaches at analyse at the bulk level so all the important detail becomes averaged out. Furthermore, given that proteins self assemble, organise and modulate electron/energy transfer system at the single molecule, there is potential for the adaptation for use as nanodevices, including molecular transistors and biomolecular electronics. The Jones groups has been involved in interdisciplinary research collaborations aimed at investigating the single molecule behaviour these systems. Proteins are engineered for specific residues to allowed defined and precise interactions with conducting surface and materials. This has led to several important developments in the area of molecular electronics and single protein molecule studies. Notably, we have demonstrated for the first time direct coupling of a protein to both electrodes allowing ET to be monitored at the single molecule level.

Our studies revealed that cytochrome b562 was remarkably conductive and exhibited transistor-like behaviour with current modulated electrochemically. We have also shown that protein surfaces can electrostatically gate conductance through nano-carbon materials so paving the way for next-generation biosensors.

Engineering proteins using an expanded genetic code

We use an expanded genetic code to engineer proteins to contain new chemical diversity. The shared genetic code restricts most organisms to the incorporation of the same 20 amino acids into proteins, thus limiting the chemical functionality available. Expansion of the genetic code to allow the incorporation of potentially useful non-natural amino acids into a growing polypeptide chain in vivo will generate proteins with novel and enhanced physicochemical and biological properties not accessible in Nature. This in turn will provide new approaches for studying both the molecular and cellular aspect of protein function and for adapting proteins for biotechnological applications. The group are developing computational approaches to predict the effect of non-natural amino acid incorporation on protein function, and to use the new chemistry to adapt proteins for use in areas ranging from novel bioimaging approaches to bottom-up bionanohybrid assembly.

Transposon-based methods for directed evolution

We have also developed a range of transposon-based technologies to sample various different mutational events not normally sampled during directed evolution. The method can be used to insert or delete multiples of three nucleotides resulting in the in-frame deletion or insertion of amino acids at random positions in a protein. Indel mutations alter the structure and hence function of protein in ways not accessible to substitution mutations alone thus expanding the sequence, structure and functional space sampled by directed evolution. We have also extended these methods to allow the replacement of one trinucleotide sequence with another either predetermined (e.g. TAG) or random (e.g. NNN) sequence. This allows directed evolution to perform a "scanning mutagenesis" function and overcome the "codon bias" problems inherent with existing directed evolution methods. The transposon-based method has also been used to create new protein scaffolds by recombining two normally disparate, non-homologous proteins, so creating novel chimeric proteins.

Funding

  • BBSRC
  • EPSRC
  • KESS
  • MRC
  • Wellcome Trust
  • Commonwealth SC

Postgraduate research students

  • Ms Rebecca Gwyther
  • Ms Rochelle Ahmed
  • Ms Athena Zitti
  • Mr Ozan Aksakal
  • Ms Lainey Williamson (2nd-supervisor).

Collaborations

Internal

External

  • Dr Matteo Palma (QMUL). Bionanohybirds for conductance
  • Dr Eugen Stulz (Southampton). Nanoscale assemblies
  • Dr Chris Pudney (Bath). Protein dynamics and fluoresence.
  • Dr Nehad Noby (Alexandria University, Egypt). Esterase structure and engineering

Teaching

Main teaching duties

1st Year. BI1001. Research Techniques

2nd Year. BI2232. Biochemistry.

3rd Year. BI3255. Synthetic Biology and Protein Engineering (Module lead). BI3001 - Final Year Project.

3rd Year. BI3008. Advanced Research Techniques. Molecular dynamic simulations.

4th Year. BI4001. Advanced Reseach Project.

Biography

After gaining my BSc in Biochemistry from the University of Wales, I studied for my PhD in protein structure and engineering at Cambridge University under the supervision of Prof Richard Perham, being awarded my doctorate degree in 1999.

My further research has centered on protein structure and engineering, having held research positions in both the academic (MRC Centre for Protein Engineering in Cambridge and the Department of Chemistry, Cambridge University) and industrial (Marie Curie Industrial Fellowship at Novozymes A/S Copenhagen, Denmark) sectors. I moved to Cardiff in September 2003.

I have served on the Biochemical Society Molecular Structure and Function theme panel, organising two successful protein engineering conferences attracting some of the top researchers from around the world. I am also UK represenatives of INPEC (International Network of Protein Engineering Centres).

Amongst my various teaching duties, I am module coordinator for BI3255 (Synthetic Biology and Protein Engineering).

Supervisions

Protein engineering, especially fluorescent protein

Construction of useful BioNanoHybrids whereby protein function as the single molecule level is used to modulate conducting materials such as nano-carbon.

Antimicrobial resistance.

Enzyme structural biology and dynamics.

Current supervision

Ozan Aksakal

Ozan Aksakal

Graduate Demonstrator

Athena Zitti

Athena Zitti

Graduate Demonstrator

Contact Details

Email JonesDD@cardiff.ac.uk
Telephone +44 29208 74290
Campuses Sir Martin Evans Building, Room Cardiff School of Biosciences, Main Building, Museum Avenue, Cardiff, CF10 3AT, Museum Avenue, Cardiff, CF10 3AX

Research themes

Specialisms

  • Proteins and peptides
  • Medical molecular engineering of nucleic acids and proteins
  • Nanobiotechnology
  • Biochemistry
  • Protein design and engineering