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Nick Waterfield

 

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WMS - Microbiology and Infection
University of Warwick
Coventry
CV4 7AL
Tel: 024 7652 2459
Email: N.R.Waterfield@warwick.ac.uk
WebLink: https://www2.warwick.ac.uk/fac/med/research/tsm/microinfect/staff/waterfieldlab/

Research Interests

My research interests focus on understanding the interaction between pathogenic bacteria and their hosts. More specifically I am interested in the molecular adaptations that can allow ubiquitous insect pathogens to evolve into human disease agents [Waterfield 2004, Nat Rev Micro]. Many feared human infectious diseases have current associations with invertebrate hosts or have evolved from their pathogens, including the etiological agents of Bubonic plague and Anthrax. I am particularly interested in the Gram-positive Bacillus cereus sensu lato group (including B. thuringiensis and B. anthracis) and the Gram-negative emerging human pathogen Photorhabdus asymbiotica. I have previously used a range of invertebrates as model infection hosts. These include insects, such as the fruit fly Drosophila and the larvae of moths, like Manduca sexta, and beetles. In addition I have used C. elegans nematode worms and amoeba, including Dictyostelium and Acanthamoeba as models. Using multiple invertebrate hosts and cultured cells I developed a screening method (RVA) for the identification of novel toxins, natural products and other virulence factors from pathogen genomes [Waterfield 2008, PNAS 105]. In addition I have discovered and characterised a range of novel protein toxins from the genus Photorhabdus, some of which have potential as pest or disease vector control agents [Yang 2012, PLoS path 8]. These include the orally active Toxin Complex, the potent Mcf-toxins, the mosquitocidal binary PirAB toxins and the Photorhabdus Virulence Cassettes (PVCs). The PVCs encode “nano-syringes” which become loaded with toxins and then released from the bacterial cell allowing delivery into host cells. My current research employs powerful post genomic techniques to understand how P. asymbiotica can infect both insects and humans. Comparative genomics, functional genomics, RNA-seq digital transcriptomics, proteomics and pheno-array studies have provided detailed insights into how this pathogen achieves this duel pathogenic state. In addition to allowing us to construct a systems level model of gene expression in different hosts, it has provided an excellent discovery platform for bioactive proteins and small drug like secondary metabolites. Such bioactive molecules include insecticides, antimicrobials and immune modulatory molecules. Furthermore our network model analysis suggests that temperature adaptation and changes in metabolic activity are crucial to this host shift from insect to man. Finally I am also interested in novel healthcare technologies, having worked on the early development of novel antimicrobial coatings [Poulter 2011, Chem Com], responsive biomimetic wound dressings and a molecular probe for detecting glycation damage of proteins [Morais 2013, Sci rep 3]. We are currently developing a controllable protein drug delivery system from the PVC nano-syringes in collaboration with Matt I. Gibson in Chemistry.

Biography

I received my Ph.D. from Gonville and Caius College, Cambridge (UK) in 1995, working in the laboratory of Richard Le Page. This work included the study of bacteriophages and gene expression in the food-grade bacterium Lactococcus lactis to develop tools for a novel mucosal vaccine delivery system. During this time I developed an interest in bacterial toxins while working on novel subunit vaccines for various bacterial toxins of veterinary interest. In 2000 I moved to the University of Bath to work as a senior postdoc with Richard ffrench-Constant on the insect pathogen Photorhabdus. I subsequently secured an academic post as lecturer and then senior lecturer at Bath. During my time as a postdoctoral scientist and the PI at Bath I developed my main research interest which lies in the relationship between invertebrate and mammalian pathogens, more specifically in how insect pathogens influence the evolution of human disease. In addition to receiving Royal Society and BBSRC research grants I have also received funding from three EU FP7 consortiums, BACTERIOSAFE, EMBEK1 and GAMEXP. The EMBEK project related to the development of novel plasma-deposited antimicrobial surfaces for bandages, catheters and medical implants. BACTERIOSAFE is concerned with the development of nanotechnology based biomimetic surfaces for responsive release of antimicrobials upon the presence of pathogens. The GAMEXP project was focused upon using genomic approaches to natural product isolation from the insect pathogens, Photorhabdus and Xenorhabdus. Many of these molecules are being developed further. I am currently using a systems biology approach to understand the evolution of human pathogenicity in the genus Photorhabdus and the role of invertebrates in the evolution of B. anthracis.

Research Projects

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Publications

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