Interrogating bacteriophages to discover the universal secrets of host-virus and virus-virus warfare

Prophages are the DNA sequences of viruses that have infected bacteria and incorporated their genetic material into the bacterial genome. Temporarily dormant, these prophages co-replicate with the bacterial host for multiple generations.

However, when a cue for reactivation is received, prophages excise themselves from the bacterial chromosome, replicate independently and reassemble the infectious viral particles that burst from the bacterial cell to search for new victims.

In addition to genes that are critical for reassembling the bacterial virus (bacteriophage) when it is activated back into life, prophages carry accessory genes for defending the host against infection by other, rival bacteriophages. Such accessory prophage genes are found on regions that are hot-spots of genetic variability.

In this project, we will discover and validate new phage defence and counter-defence mechanisms via mining virus genomes for variable hot-spots that contain the arsenals of genes for attack and defence.

Through sensitive sequence and structure analysis with state of the art bioinformatics methods, we are able to reveal the true extent of this arsenal, finding related protein domains that are also used in human defence against viruses, and counter-defence systems that allow human-infecting viruses to evade the host immune system.