Profile: Professor Brendan Wren
Professor Brendan Wren from the Pathogen Molecular Biology Unit talks about his career and research
"I became a microbiologist by chance. I started life as a physical chemist studying the effect of ionising radiation on the atomic structure of DNA at Leicester University. In 1985 I decided to work on something larger and living, and researching on single celled bacteria seemed a logical choice. This change in career took me to the Medical Microbiology Department at St Bartholomew's Hospital, London, where working alongside clinicians and MLSOs gave me a close up view on the importance of bacterial pathogens. I had intended to move on to work on more complex eukaryotic systems, but the intricacies of the bacterial cell and how it can cause disease have held my interest ever since.
In 1999 my research group and I moved to the School where our current research centres on the molecular characterisation of enteric pathogens. These include Campylobacter jejuni, a major food borne pathogen worldwide and the leading cause of Guillain-Barré syndrome, Helicobacter pylori, the causative agent of gastric ulcers and associated with gastric cancer, Clostridium difficile, the leading cause of antibiotic-associated colitis and pseudomembraneous colitis and enteropathogenic Yersinia. Individual projects focus on the genetic regulation of virulence (e.g. two component regulatory systems), bacterial-host cell interactions (e.g. polysaccharide surface structures and type III secretion systems) and the characterisation of dedicated virulence determinants (e.g. toxins, phospholipases and haemolysins). Essentially, we are interested in determining the attributes that make certain bacteria pathogenic, compared with the vast majority of bacteria in the biosphere.
In collaboration with Sanger Centre staff, we are actively involved in deciphering the genome sequences of C. jejuni, C. difficile and pathogenic Yersinia. The genome sequence of pathogens provides us with the full itinerary of genes and gene products encoding all virulence determinant and vaccine candidates. We now have all the words in the dictionary and through functional genomics technologies we are in the process of determining the meaning of each word to enable us to have a comprehensive understanding of what makes these problematic pathogens work.
More recently our attention has focussed on developing innovative technologies to exploit sequence information generated from genome projects. In particular we have constructed C. jejuni, H. pylori and pathogenic Yersinia. DNA microarrays that allow high-throughput DNA or mRNA hybridisation to interrogate the whole genome. We are co-founders of the microbial pathogen microarray facility housed at St George's Hospital and are currently constructing whole genome DNA microarrays for other pathogens including C. difficile, Mycobacteria tuberculosis and Chlamydia spp.
The LSHTM is the finest working environment that I have experienced. There are unique opportunities for teaching and researching, entailing the A to Z of infectious disease - from DNA molecule to decision-making. A particularly appealing aspect of working at the School has been my direct interaction with postgraduates through lectures, seminars and through students spending a sustained period of time in the laboratory.
The availability of whole genome sequences of pathogens, vectors and hosts will provide unprecedented opportunities. We are on a voyage of discovery. The long-term aim is to gain a fully rounded understanding of the complex ways in which pathogens modulate virulence and interact with the human host. Such a holistic approach will vastly increase the scope for the rationale of design of intervention strategies to reduce the burden of infectious disease. What a particularly fine time to be a microbiologist!"
Dr David Baker also works in the Pathogen Molecular Biology Unit
