Infectious diseases are among the leading causes of morbidity and mortality in the developed and developing world. Bacterial pathogens are highly adaptable and horizontal transfer of DNA between isolates allows rapid acquisition of new traits, particularly those under acute selective pressure like antibiotic resistance and pathogenesis in new hosts (e.g.: zoonoses).
A major focus in the lab is enterohaemorhaggic E. coli (EHEC), a pathogenic cousin of the harmless, commensal E. coli species in our normal floral. EHEC causes sporadic outbreaks of disease when it enters the food chain, often through contaminated meat or vegetables. Infection is often associated with diarrheal disease, but can progress to potential fatal haemolytic uremic syndrome. Genome sequencing has demonstrated that EHEC has horizontally acquired an extra ~1.5Mb of DNA when compared with its commensal E. coli cousin. The extra DNA has been transferred into the genome on an array of mobile genetic elements including about 24 cryptic and active prophage elements (bacterial viruses integrated into the genome), that carry the lion’s share of virulence genes.
We are interested how bacterial pathogens control the extra genetic information that is transferred on these mobile elements. Much like new hardware requires new software to control how it operates, we are interested in what regulatory information controls the pathogenic hardware transferred between bacteria.
To this end, the lab has is exploring an exciting area of bacterial gene regulation, termed regulatory non-coding RNAs. In essence, these are short (50-500nt), untranslated RNAs that control gene expression post-transcriptionally (after an mRNA is made from the gene). Using high-throughput techniques to study RNA-protein interactions and RNA-RNA interactions, we have shown that the extra ~1.5Mb of DNA in EHEC is rich in regulatory non-coding RNAs. We have also developed a technique for studying their functions within the cell. Using these tools we are dissecting the regulatory software that is “installed” into this important human pathogen and are understanding how it is rewired for pathogenesis.