Non-Coding RNA Regulation of the Whooping Cough Vaccine Antigen, Pertactin

My lab has an ongoing interest in how complex genetic traits such as virulence are regulated and selected in bacterial pathogens. Non-coding RNA (ncRNA) regulation has come to the fore with the advent of RNA sequencing and it has been demonstrated that bacterial pathogens produce hundreds of ncRNAs. However, we have a poor understanding of the function of the majority of these RNA species. The functions of bacterial ncRNAs are likely to be exceptionally diverse, and we are using UV-crosslinking and deep sequencing techniques to study these processes and reveal novel mechanisms of gene regulation.

Bordetella pertussis is the causative agent of whooping cough, a respiratory disease responsible for 200,000 deaths and 40 million cases worldwide. The pertussis acellular vaccine contains three antigens, one of which is the adhesin pertactin, conferring protective immunity. Recently, there has been an increase in the number of cases of whooping cough among vaccinated individuals. Investigation of currently circulating isolates has revealed that a large proportion no longer express the pertactin antigen. Some pertactin deficient isolates still express mRNA, suggesting that expression is silenced post-transcriptionally.

This project will investigate the mechanisms behind silencing of pertactin with an emphasis on understanding the roles of non-coding RNA regulation of this important vaccine antigen. The project will be co-supervised by Associate Professor Ruiting Lan.

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