Key research interests and discoveries. 
I am interested in the interaction between bacteriophages and their hosts in particular in the antibiotic producing, mycelial, soil bacteria, Streptomyces.

The mechanism and applications of serine integrases. We were the first to describe the biochemical properties of this group of phage-encoded integrases. These enzymes drive the site-specific recombination between a phage genome and the host chromosome, a process that is required for entrance and exit from a latent growth cycle by temperate phages. The programmable nature and specificity of the phage integrases resembles how we precisely ‘cut and paste’ text using a computer, and this precision and predictability has led to wide applications for the integrases in genetic engineering.  We are currently interested in applying these enzymes to facilitate the engineering and optimization of antibiotic pathways in Streptomyces and other hosts for industrial microbiology. In our group these applications have been informed by a detailed understanding of how these integrases work and, in particular, how they are controlled.

 Phage receptors and the role of protein O-glycosylation in Streptomyces coelicolor.  General protein glycosylation pathways in bacteria have only recently been described and the nature and roles of the glycan moieties are poorly understood. A protein O-glycosylation system, similar to the O-mannosylation pathway in fungi and humans, is rife in the Actinobacteria. We have shown that protein O-glycosylation is important to the growth of Streptomyces bacteria, in particular the process seems to be essential for innate resistance to many antibiotics. We aim therefore to understand the role of glycosylation in secreted and membrane bound glycoproteins and how this modification can provide insights into antibiotic targets.

 The evolution of phage genomes and the diversity of phage defense systems in bacteria. I have always wondered how phages adapt to their different microbial hosts. This is the question that has driven me right from my very first academic position and is particularly pertinent to phages such as Streptomyces phage that grow in a mycelial, sporulating host. Equally interesting are the host’s defense systems that have evolved to control phage predation and we have studied a unique ‘phage growth limitation’ system in Streptomyces.  Recently systems related to ‘pgl’ have been shown to be widely distributed in all bacteria.