our research

We are investigating temperate bacteriophages that form cooperative partnerships with their bacterial hosts. We are using several approaches to unveil previously unknown functions.

This work will lead to a better understanding of how bacteria survive in the body and cause disease and may even inform new strategies for treatment.

Lytic bacteriophages could help combat antibiotic resistant bacteria, but temperate phages effect bacterial biology differently and can make them more dangerous. This is an image taken using scanning electron microscopy. It shows a bacterial cell that is inhabited by a temperate phage, which has been triggered into a lytic cycle bursting the bacterium open to release new infectious phages. Find out more in this review (image ref: Future Microbiol. 2007 2(2):165-74. doi: 10.2217/17460913.2.2.165.)

The Two Main Bacteriophage Life Cycles

This diagram summarises what we know about the two main life cycles of bacteriophages. The temperate phages that we work with can switch between the lysogenic and the lytic cycles. Although we know the basics, phages employ different strategies to do this.

By uncovering the function of unknown phage genes we can understand these processes and how they are controlled much better.

Our research approach

The phage genetic code is mostly a mystery (dark matter), including genes unlike any others. We are trying to determine the function of these genes and how they enable phages to act like puppet masters, controlling different bacterial activities. Our work focuses on phages that cohabit within the DNA of Pseudomonas aeruginosa, a bacterium that can cause severe and chronic lung infections, particularly in people with cystic fibrosis. Our strategy for this project is to first identify all the genes in the bacteria and phages that are turned on during lysogeny and during lytic replication. The second step is to map the function of the genes we find expressed by the bacteria to known cell functions to identify traits we can test in the laboratory. The next step is to identify expressed phage genes and test their the ability of select phage genes to drive the bacterial traits we have identified. With further confirmatory experiments we hope to assign function to some of the phage genes we identify, unveiling some important functions of phage dark matter, and gaining a better and deeper understanding of how phages control, or act as puppeteers of their bacterial cells. From this point, we can design new phage-focused strategies to tackle bacterial infections.

**How we work with phages**: We use an experiment called a plaque assay to grow and count active phages. This picture shows phages that have been pipetted onto a bacterial lawn of bacteria to draw a smiley face. The tiny holes are caused by phages killing and replicating in the bacterial cells and bursting them open to then infect more of the surrounding bacteria. Eventually so many bacteria have been burst open that a cleared patch is visible to the naked eye. This is called a plaquewithin that area of the lawn

These are transmission electron microscope generated images of the 3 phages of Pseudomonas aeruginosa that we are focusing on. They co-habit a strain of Pseudomonas aeruginosa called The Liverpool Epidemic Strain (LES).

Our previous research suggests that the LES phages help this strain to survive in the lungs and we are trying to find out how. See our publications to find out more. You can see more information on their genomes and the information we have learned.

Engaging with the data: Computing is an essential part of modern biological research. Often called bioinformatics, this rapidly evolving approach uses computational analysis software to explore big data sets like The Human Genome sequence. A genome is the term used to describe all the genetic code of an organism. It is the entire blue print for what that organism looks like and how it works. The diagrams above represent the genomes of the bacteria we work with and the phages that inhabit them. When a phage genome is incorporated into the genetic code of bacteria, it is becomes a “prophage” and it can fundamentally change the evolutionary trajectory of its bacterial host. Sometimes this can create a more dangerous bacterial pathogen, but there are more subtle changes that can control multiple bacterial functions. This is where the term “Puppet Master” comes from.

The top diagram shows a series of coloured rings. Each represents the genome of one of our model bacteria. The red, blue and green arrows represent the prophages and show the different places where we have found them incorporated. By integrating into different locations on the bacterial chromosome the phages can cause mutations and change how the bacteria behave. The lower diagram shows a series of coloured arrows that represent all the genes of each prophage we are studying. Each colour represents a different type of gene function. Many of the genes are white. This means that their function is unknown. Some are called “hypothetical genes” which have all the hallmarks of a gene but their DNA sequence has never been seen before hence their function has never been determined. This is called “dark matter” and we are working to unveil these functions.