The “superbug”, Methicillin resistant Staphylococcus aureus (MRSA) is a major threat to global health. Bacteria can sense external stresses such as nutrient deprivation, which promotes antimicrobial tolerance and drives chronic infections. The transition from colonisation to infection is exceptionally stressful for bacteria, as is treatment with antibiotics. To cope, they activate complex regulatory circuits controlled by two “alarmone” phospho-nucleotides that signal this stress, regulating bacterial functions in ways that maximise survival. The two nucleotide alarmones are guanosine tetraphosphate and guanosine pentaphosphate, which are produced specifically in response to stress and are responsible for coordinating cellular events that turn off growth and turn on genes for stress adaptation, antibiotic tolerance and survival. Whilst alarmone signalling has been linked to persistent and chronic infections, little is known about how they function to coordinate this adaptation on a molecular level in living animals.
We have pioneered zebrafish as a powerful model for imaging infection and host-pathogen interactions in vivo and have a range of transgenic lines marking immune cell populations. In parallel, we have generated alarmone-deficient S. aureus. You will use these strains in live transgenic zebrafish under high-resolution confocal microscopy to probe the role of alarmone responses in bacterial virulence and antibiotic tolerance. You will define the mechanisms through which alarmones drives adaptation to stress within the host. You will generate fluorescent reporter strains to see bacterial stress responses in vivo for the first time ever. You will make major advances in our understanding of the superbug and help find new ways to treat it.
All the techniques and approaches are established in our groups and we have busy and successful labs with plenty of people to help with your training. All the tools are ready and waiting to go, making a publication within the first half of the PhD a real possibility. We provide training in writing, presenting and science outreach, as well as bench science and you will work in an exciting and thriving community of like-minded scientists in the Florey Institute (http://www.floreyinstitute.com/
A 3.5–year PhD studentship is available. The studentship comes with full tuition fees and is available to UK/EU students. Stipend is at the standard UKRI rate (currently £14,777 pa).
We are looking for an enthusiastic student interested in joining our group at the Florey Institute (View Website). This project is fully funded through a Lister Institute Research Prize.
You should possess a high 2.1 or 1st class degree in microbiology, biochemistry or immunology/cell biology. Relevant laboratory experience is not required, but passion and enthusiasm for making a difference in the field of antimicrobial resistance is a must!