Broad host range bacterial pathogens are bacteria that can cause disease in many different kinds of hosts. The goal of the work in this proposal is to understand how broad host range bacterial pathogens are affected by their interaction with non-human hosts and how this interaction changes their biology in ways relevant to human disease.
This proposal focuses on the interaction of the bacterium Listeria monocytogenes with the fruit-fly Drosophila melanogaster. Drosophila is the best-studied insect, and a great deal is known about its immune response. Listeria is common in the environment, particularly in decaying organic matter, and it interacts with many different animal host species; in humans, Listeria can cause serious food poisoning.
Listeria must survive the immune responses of a variety of hosts. However, this is complex: different animals' immune systems work differently, and mechanisms that allow bacteria to escape killing in one host are often unhelpful in another. We don’t know whether Listeria functions differently in infecting different animals or how the pressures imposed by other hosts will affect the ability of Listeria to infect humans.
We will approach this using experimental evolution. We will infect fruit-flies with Listeria and collect the bacteria that are still present several days later. We will then use these bacteria to infect another set of fruit-flies, again collecting the surviving bacteria. Over time, the bacteria evolve to become more able to survive in fruit-flies. We will then identify the genetic changes in these evolved bacteria using genome sequencing and test their interaction with antibiotics and human immune cells as well as seeing how their ability to infect fruit-flies has changed.
Techniques: Early stages of the project will involve simple microbiology (isolating bacteria from Drosophila) and general Drosophila work. Middle stages will become more technical (generation and analysis of bacterial genome sequence data). The late stages of the project will depend on earlier findings but are likely to include bacterial and/or host genetics, gene expression analysis (qRT-PCR), mammalian tissue culture, and confocal microscopy.
Studentships are expected to last for 36 months, subject to satisfactory progress. A BSc in biological, or related, sciences is required at Upper Second Class level or better and candidates with a Master's degree, in addition to the BSc, might be given preference.