Research within the Wren group predominantly involves determining the genetic basis by which bacterial pathogens function, evolve, cause disease, and how they develop antimicrobial resistance (AMR). Research on individual pathogens include Clostridium difficile, Campylobacter jejuni, Helicobacter pylori, Burkholderia pseudomallei, Acinetobacter baumannii, Francisella tularensis, Streptococcus pneumoniae, Streptococcus suis, Actinobacillus pleuropneumoniae, Vibrio cholerae, group A and group B streptococci (GAS and GBS) and the enteropathogenic Yersinia.

A core interest within the group has focused on bacterial glycostructures, including the characterization of lipo-oligosaccharides, capsular polysaccharides and glycosylation systems. This basic research has enabled us to develop glycoengineering tools in E. coli through a process termed Protein Glycan Coupling Technology (PGCT) or bioconjugation. The major application of this biotechnology is the production of more affordable recombinant glycoconjugate vaccines. To date, we have used the technology to produce novel recombinant Campylobacter, S. pneumoniae, Francisella, Brucella and Shigella glycoconjugate vaccines candidates for human and veterinary use.

Bacterial pathogenesis

The team researches many different aspects of the pathogenicity and AMR of Streptococcus pneumoniae, group A and group B Streptococci (GAS and GBS), Campylobacter jejuni and Clostridium difficile.

These include gaining further insights into the incidence and virulence of Streptococcus species (S. pneumoniae, GAS and GBS), especially S. pneumoniae serotype 1, which is amongst the most common serotypes associated with invasive pneumococcal disease (IPD), particularly in Sub-Saharan Africa, South America and Asia where it is often associated with outbreaks, as well as improving mutagenesis tools to study clinical isolates and developing targeted bioconjugate vaccines.

In Campylobacter research we explore the role of oxidative and aerobic stress response mechanisms during bacterial interactions with hosts cells and survival in the environment; the role of outer membrane vesicles (OMVs) in the delivery of bacterial effector proteins into host cells; the role of the Type VI Secretion System (T6SS) during bacterial interactions with hosts cells and survival in the environment; the genetic mechanisms controlling the biogenesis of OMVs; the role of the Unfolded Protein Response during C. jejuni intracellular survival; the interactions between amoebas hosts and bacteria and their role as bacterial reservoirs. Further studies with both government and industrial collaborators are investigating potential intervention strategies to reduce the survival of C. jejuni in chickens using microbiome-based approaches.

We specialise in a genome to phenome approach to understand virulence traits of the important human pathogen C. difficile and to decipher C. difficile interactions with the host microbiome. We intend to elucidate the inhibitory role of para-cresol, a phenolic compound produced by C. difficile on the host microbiome; to dissect lifestyle switching between vegetative cells, spores and biofilms and its role in colonisation and relapse of C. difficile infections and to identify and characterise immunogenic proteins and their potential use in vaccine development.

Glycoengineering and Vaccine development

The team researches fundamental and translational questions about glycosylation systems in bacteria. The research that we are carrying out begins by asking why some bacteria have glycosylation systems and tries to understand how these are regulated. We also have a thriving body of work researching methods to optimise glycoconjugate assembly using biological conjugation systems. We term this process, Protein Glycan Coupling Technology (PGCT). In addition, we investigate how to express polysaccharide coding regions heterologously, a method we term Glycan Expression Technology (GET). Several of our projects are focusing on the application of the latest glycoengineering knowledge to develop novel solutions for both human and animal diseases with a strong emphasis on the development of glycoconjugate vaccines against bacterial infectious diseases of global concern.