Centre for Synthetic Biology and the Bioeconomy

Staff Profile

Dr David Fulton

Senior Lecturer in Chemistry

Background

Biography

David Fulton received his BSc (Hons) from Strathclyde University and PhD from the University of California, Los Angeles, working on carbohydrate and supramolecular chemistry under the direction of Prof Sir J Fraser Stoddart FRS.  He then spent two and half years as a postdoctoral research associate with Prof David Parker FRS at the University of Durham working on the synthesis of gadolinium-centered dendrimers as new MRI contrast agents.  In 2006 he moved up the road to take up his present position within Chemistry at Newcastle University where he is a member of its Functional Materials and Molecules group.  His research interests are broadly based upon supramolecular/synthetic polymer chemistry.

Qualifications

PhD University of California, Los Angeles, 2001
BSc (Hons) University of Strathclyde, 1996

Previous Positions

Postdoctoral Research Associate, Durham University, 2003-2005
Analytical Method Development Chemist, Quintiles Ltd, 2002
Process Development Chemist, Merck Ltd, 1994-1995

Area of Expertise

Supramolecular polymers and materials.

Google Scholar

https://scholar.google.co.uk/citations?user=NDGx0nAAAAAJ&hl=en


Research

Dr David Fulton has broad interests in polymer and supramolecular chemistry. Projects have received support from EPSRC, Innovate UK, The EU-framework 7 program, industrial partners and The Royal Society. Some current projects are summarized.

Polymers and materials from bacterial fimbriae. For millennia, humans have exploited fibres produced by animals and plants to make materials such as textiles and paper.  Many strains of bacteria also produce hair-like fibres called fimbriae that have evolved unique structural and mechanical properties that make them appealing building as the foundation for new materials, however, these possibilities are still essentially unexplored.

Working closely with the laboratory of Prof Jeremy Lakey at Newcastle, we have developed the first examples of materials based upon Capsular antigen fragment 1 (Caf1) (Fig. 1a), the fimbriae produced in nature by Yersinia Pestis, the bacterium responsible for the bubonic plague.

Caf1 polymers (~ 1 µm)  are chains of 15 kDa monomer subunits, each non-covalently linked to a single neighbouring subunit by a donated N-terminal β-strand.   Caf1 has evolved its structure to inhibit interactions with host cells, helping the bacterium hide from the immune system.  Caf1 bears a structural resemblance to fibronectin—a naturally occurring extracellular matrix—suggest Caf1 has great potential as a biomaterial for advanced cell culture.  It is possible to ‘hard-wire’ cell adhesion peptides into surface loops of the Caf1 protein, presenting a straightforward way to engineer bioactivity whilst avoiding chemical functionalization with expensive peptides. This structural similarity to ECM proteins, together with its other highly desirable properties (non-adhesion, stability and ease of production) endow Caf1 with features that are difficult to design de novo into protein polymers. Furthermore, Caf1 is produced by bacterial fermentation and thus does not suffer from the batch-to-batch variability of animal-based materials such as Matrigel®.

It is easy to chemically cross-link Caf1 polymers into hydrogel materials (Fig. 2a,b), 3D polymer networks possessing high water contents and porous structures, properties they share with the extracellular matrix.

Caf1 also has some hidden and unexpected features.  The linkages between subunits in the Caf1 are exceptionally strong and kinetically very inert, however, we discovered that heat can be used to reversibly cycle Caf1 between its polymeric and monomeric states (Fig. 3), a feature that endows the Caf1 polymer with new synthetic and materials possibilities.  This has allowed us to prepare copolymers featuring controlled compositions of naturally-occurring and mutant subunits, and to encapsulate live cells within a cross-linked Caf1 matrix.


Dynamic Covalent Polymers. Dynamic covalent chemistry relates to chemical reactions carried out under conditions of equilibrium control, and exploits dynamic covalent bonds (DCBs), which like non-covalent bonds display a dynamic nature but which also possess the chemical robustness associated with all covalent bonds.  The term ‘dynamic covalent bond’ simply describes any covalent chemical bond which possesses the capacity to be formed and broken under equilibrium control, and encompasses many well-known functional groups such as imines, esters and hydrazone.  At Newcastle we have been utilizing DCBs to endow polymeric systems with the abilities to adapt their structures or compositions in response to an external stimuli.  When DCBs are incorporated into polymeric systems, the reversible nature of bonds enables these systems to modify their architectures by reshuffling, incorporating or releasing their components, in effect providing a mechanism for polymer systems to reconfigure their molecular structures and therefore their functional or material properties.

One way we have utilized these ideas is in the development of polymer-scaffolded dynamic combinatorial libraries which we have shown respond to the addition of macromolecular templates by changing their compositions, preferentially incorporating residues which promote binding and rejecting residues which do not.  This work might lead to a new method to make artificial receptors for sensing and separations.

We have also developed dynamic covalent polymers which are able to undergo structural metamorphosis from an intramolecularly cross-linked polymer chain into cross-linked gels or films, and we are working to develop this approach to allow the ‘wrapping’ of small biological objects such as viruses or bacteria within cross-linked polymer films.

Polymers for Industrial Applications. Polymers have been a component of detergent/cleaner formulations for many years, where their purpose is to improve product performance.  Many of these polymers, however, are petrochemical-based with worldwide consumption > 130,000 tonnes p/a.  Concerns regarding depletion of fossil resources, disposal and related issues, as well as evolving government policies, are driving the search for alternatives, and there is now an urgent need to develop bio-based and biodegradable alternatives to petrochemical-based polymers.  Polysaccharides are of considerable potential as they are usually derived from sustainable plant sources and are associated with low toxicity and excellent biodegradability.  We are working in collaboration with Procter & Gamble to develop new polysaccharide biopolymers derived from sustainable feedstocks that create novel functionalities including polymers that entrap hydrophobic guests within their 3D structures (potential for dye transfer inhibition, hydrophobic soil suspension) and as flexible amphiphilic polymers (beneficial for anti-redeposition). 

The fouling of surfaces by marine organisms presents a substantial problem, leading to reduced vessel performance and increased costs. Traditional solutions have involved antifouling coatings which leach biocides (often based upon tin or copper) but because of the adverse impact caused by the release of toxic compounds into the environment these coatings are either banned or under increasing regulatory scrutiny.  Working with Akzo Nobel and Solvay, we have developed zwitterionic foul-release polymer coatings which display potential in marine antifouling applications.

Teaching

Undergraduate Teaching

Stage 2 Organic chemistry (CHY2101): Module leader and lecturer (24 lectures).

Stage 3 Organic chemistry (CHY3108/5): Lecturer (12 lectures).

I also contribute to a number of other modules including final year MChem project supervision( CHY8511) and MSc project supervision (NES8002).

Publications