Skip to main content Skip to navigation

Nick R Waterfield

In the Waterfield group we are interested in understanding the molecular mechanisms and ultimately exploiting natural bacterial toxin systems for biotechnology purposes.

To do this, we routinely use cutting edge molecular biology and genomics techniques to rationally alter and edit natural systems such that they can perform tasks of interest to us. The Gram-negative pathogen Photorhabdus deploys a wide diversity of protein toxin delivery systems. We are currently studying the molecular mechanisms of several such systems. How are they targeted? Can they be adapted for medical or agricultural purposes? These projects are necessarily interdisciplinary and so we engage with inter-department projects. More specifically with Prof Matt Gibson; a polymer and biomaterials chemist and Prof Peter Scott; on novel antimicrobials, both from the Warwick Chemistry department.

picture1.png

Another major focus in the group is Natural Product drug discovery, specifically from the insect pathogen Photorhabdus. Importantly, all natural products serve specific biological roles unlike the majority of molecules in synthetic compound libraries. If we can determine their activities we may exploit them for unmet medical or agrochemical needs. The majority of natural products produced by Photorhabdus are used to kill their insect host or combat competitors and predators, thus presenting a useful source of potential novel insecticides and antimicrobial drug candidates. In order to combat the rising threats of antibiotic and pest/parasite drug resistance, we need to develop novel compounds that exhibit new modes of action distinct from those of current drug targets. We are currently developing an imaginative trans-disciplinary methodological pipeline that will grant access to the wealth of cryptic natural products inferred from bioinformatic analysis of the genome sequences of the insect and human pathogenic genus Photorhabdus. These bacteria are sufficiently closely related to E. coli that many available synthetic biology genetic tools are applicable.

Selected publications:

From Insect to Man: Photorhabdus Sheds Light on the Emergence of Human Pathogenicity.

Mulley G, Beeton ML, Wilkinson P, Vlisidou I, Ockendon-Powell N, Hapeshi A, Tobias NJ, Nollmann FI, Bode HB, van den Elsen J, Ffrench-Constant RH, Waterfield NR. PLoS One. 2015 Dec 17;10(12)

 

The role of TcdB and TccC subunits in secretion of the Photorhabdus Tcd toxin complex.

Yang G, Waterfield NR. PLoS Pathog. 2013;9(10):

 

Rapid Virulence Annotation (RVA): identification of virulence factors using a bacterial genome library and multiple invertebrate hosts.

Waterfield NR, Sanchez-Contreras M, Eleftherianos I, Dowling A, Yang G, Wilkinson P, Parkhill J, Thomson N, Reynolds SE, Bode HB, Dorus S, Ffrench-Constant RH. Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15967-72.

 

Photorhabdus virulence cassettes confer injectable insecticidal activity against the wax moth.

Yang G, Dowling AJ, Gerike U, ffrench-Constant RH, Waterfield NR. J Bacteriol. 2006 Mar;188(6):2254-61.