Most antibiotics target rapidly dividing bacteria. However, for the majority of their existence, bacteria grow in conditions where a few or most nutrients are limiting so that very little to no propagation takes place. When resources become available, they rapidly spread, returning to a resting state as soon as nutrients become limiting again. These low metabolic states are important to disease as most antibiotics treat rapidly dividing microorganisms, and bacteria can prolong growth arrest in order to evade antibiotic action.
During growth arrest, very little protein synthesis occurs, as this is one of the most energy-expensive processes in a cell. However, amino acid building blocks are still needed, as some proteins need to be produced, such as chaperones and those that maintain DNA and RNA integrity. My work is focused on Pseudomonas aeruginosa, a human pathogen and a model organism that colonizes diverse environments with the constant need to adapt to changes in nutrient availability.
This project is centred on the following fundamental questions:
1) when nutrient deprived, will bacteria degrade their own proteins so that amino acids can be used as energy source or building blocks?
2) Would they rather degrade extracellular proteins from neighbouring bacteria?
3) How is bacterial “self-sacrifice” regulated, and what is its contribution for population survival?
4) Is there a relationship between protein degradation of intra/extracellular targets and survival?
Broadly, this project will uncover whether bacteria regulate protein degradation, so it occurs in a controlled fashion targeting components inside and/or outside of a cell when nutrient limitation occurs.
To answer these questions, we will study three classes of enzymes that play important roles in protein turnover and homeostasis.
· Enzymes that tag other proteins for degradation.
· Enzymes that remove destabilizing N-terminal residues from proteins, effectively rescuing them from degradation.
· Extracellular proteases.
This project is in collaboration with Dr Bergkessel (University of Dundee, co-supervisor, geneticist) and Dr Shirran (St Andrews, mass spectrometry facility), and will provide training in bacterial genetics, enzymology, and proteomics. Such comprehensive approach is unprecedented and will unveil crucial findings in basic and applied bacterial metabolism.
HOW TO APPLY
Application instructions can be found on the EASTBIO website- http://www.eastscotbiodtp.ac.uk/how-apply-0
1) Download and complete the Equality, Diversity and Inclusion survey.
2) Download and complete the EASTBIO Application Form.
3) Submit an application to St Andrews University through the Online Application Portal
Your online application must include the following documents:
- Completed EASTBIO application form
- 2 References (to be completed on the EASTBIO Reference Form, also found on the EASTBIO website)
- Academic Qualifications
- English Language Qualification (if applicable)
Unfortunately due to workload constraints, we cannot consider incomplete applications. Please make sure your application is complete by the 16th December 2021.
Queries on the project can be directed to the project supervisor.
Queries on the application process can be directed to Jess Fitzgerald at firstname.lastname@example.org
Please refer to UKRI website and Annex B of the UKRI Training Grant Terms and Conditions