Dr Andrew J Roe - Research Interests
I carried out a BBSRC-CASE studentship in the laboratory of Prof Ian Booth (University of Aberdeen) focused on understanding the physiology and biochemistry involved in E. coli response to acid stress. This led onto a Wellcome Trust research position in which I investigated the expression of the two-component potassium transport system, Kdp. I then joined Professor David Gallys DEFRA funded group at University of Edinburgh studying the regulation of type three secretion systems (T3SS) in E.coli O157:H7 which was a good opportunity to gain greater experience in molecular biology and work on this important pathogen. I now collaborate closely with Prof. Gallys group and the Moredun Research Institute (Professor David Smith) to enable the cellular and veterinary aspects of this disease to also be addressed.
My work investigates the function and regulation of virulence factors produced by E. coli O157 (see Figure 1). A range of molecular techniques are employed to understand when and how virulence factors are expressed. These include gene fusions to green fluorescent protein (GFP), trancriptome analysis (RNA-seq) and a range of other omic analyses including metabolomics and proteomics. An important aspect of my work is trying to understand how bacteria co-ordinate the expression of multiple virulence factors not only globally but also at the single cell level. This work is coupled to techniques that mimic appropriate interactions in the host using cell lines and tissue culture techniques.
Figure 1: regulatory control of the E.coli O157 LEE. This figure summarises the work of many groups; adapted from Spears et al., 2006 (FEMS Microbiology Letters)
Our goals are to apply our understanding of the regulation of virulence factors to develop novel intervention strategies to combat not only E. coli o157 but also the wider range of pathogens that use the same basic mechanisms for infection. In collaboration with Prof Mikael Elofsson (Umea, Sweden) and Dr Rommie Amaro (University of California, San Diego) we are developing compounds that block the expression of the type three secretion system without affecting bacterial growth or survival. Long-term, this could lead to an entirely new class of anti-bacterial agents to treat important infections.
As the interaction of the bacteria and its host cell is understood we try and model these processes to allow visualization and a better understanding of infection dynamics. As an example, we have developed a 3D animation detailing the genetic regulation of E.coli O157:H7 and its interaction with the bovine gastrointestinal tract. This movie was featured in the August 2004 issue of Microbiology Today, published by the Society for General Microbiology.
The article that accompanies the movie is "EHEC O157:H7 - getting to the bottom of the burger bug" and an electronic copy can be obtained by clicking here.