Characterising the mechanisms behind bacterial survival and antimicrobial tolerance in host cells using live-cell imaging
Our work is focused on understanding how the human pathogen Staphylococcus aureus can survive, promote antimicrobial tolerance and chronic infections, when starved of nutrients. Upon infection of host tissues, bacterial cells experience massive changes in environmental conditions. To cope, they possess a complex regulatory circuit controlled by two nucleotides (ppGpp/pppGpp), which maximise survival. (p)ppGpp is responsible for coordinating cellular events that result in the “suppression” of pathways involved in active growth and the expression of genes involved in stress adaptation, antibiotic tolerance and survival. Whilst (p)ppGpp-dependent signalling has been linked to persistent and chronic infections, little is known about how these nucleotides function to coordinate this adaptation on a molecular level. Our previous investigations have generated a strain that cannot generate (p)ppGpp in S. aureus. We will use this strain to probe the role of (p)ppGpp-driven responses in bacterial virulence and antibiotic tolerance by defining the mechanisms through which it drives adaptation to conditions within the host. This work will use live-cell imaging of zebrafish embryos as a model of infection. This will be in combination with genetic manipulations and the construction of fluorescent reporter strains to use in our state-of-the-art microscope facilities. Altogether this work will greatly enhance our understanding of staphylococcal virulence, knowledge that will contribute to the development of novel therapeutics.
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) to help us understand more about host-pathogen interactions. This project is fully funded through a Lister Institute Research Prize. Applicants should possess a high 2.1 or 1st class degree in microbiology, biochemistry or immunology/cell biology.
How good is research at University of Sheffield in Biological Sciences?
FTE Category A staff submitted: 44.90
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