PhD -Investigating the role of two-component signalling systems as mediators of adaptive antimicrobial resistance in Pseudomonas aeruginosa
PhD @University of Dundee posted 3 days agoJob Description
- Funding – self-funded/externally sponsored applicants (PhD Fees can be found here)
- Applications are accepted year round
- Standard Entry dates – January and September
- Applicants are expected to have a degree (equivalent of Honours or Masters) in a relevant discipline.
Bacteria sense and respond to their environment via intricate networks of signalling systems. Two-component signalling (TCS) systems comprise a sensor kinase that detects environmental signals and a response regulator that alters gene expression to promote adaptive phenotypic change. This ability to detect and respond to a fluctuating environment underpins adaptive antimicrobial resistance, whereby the susceptibility of a microbe to antibiotics changes as a function of its environment.
Pseudomonas aeruginosa encodes for around 60 TCS systems, affording it phenotypic plasticity that contributes to its success as an opportunistic pathogen in different host tissues. Drug tolerance and resistance in P. aeruginosa is a major barrier to treatment, especially in chronic infection.
This PhD would investigate the contribution of TCS to P. aeruginosa antimicrobial tolerance in different infection contexts. The student will address fundamental questions in infection biology, including:
- Which TCS systems underpin drug tolerance or resistance in different infection environments.
- What are the environmental triggers for TCS-mediated resistance.
- How does TCS-induced microbial physiology determine resistance.
The student will generate P. aeruginosa fluorescent reporter and gene deletion strains for individual TCS genes and will use these in phenotypic screens with an antibiotic panel that includes agents with different modes of action. Screening will be undertaken in environments reflective of various infection contexts. After determining which TCS systems are active in which environments and which contribute to tolerance to each drug class, the student will profile the testing environments to determine the physical or chemical cues for TCS signalling and will characterise bacterial physiology to determine the mechanisms of drug resistance.
Training will be provided in laboratory microbiology and molecular biology. The student will have the opportunity to learn skills in high-throughput compound screening, advanced microscopy and flow cytometry techniques, mutagenesis, phenotypic assays and big data approaches including RNA-seq and proteomics. The project will benefit from the expertise and facilities of the Drug Discovery Unit. Ongoing collaborations with industry on antimicrobial drug development projects offer opportunities for the student to broaden their professional network and to share their findings with key stakeholders.
The PhD offers an opportunity to address a major global health challenge, by contributing to the fight against accelerating antimicrobial resistance. Improved understanding of how TCS systems contribute to phenotypic resistance may uncover new avenues for therapy or help us to make informed choices of which drug to use in which infection contexts.
Our research community thrives on the diversity of students and staff which helps to make the University of Dundee a UK university of choice for postgraduate research. We welcome applications from all talented individuals and are committed to widening access to those who have the ability and potential to benefit from higher education.
How to apply
Please contact the principal project supervisor to discuss your interest further, see supervisor details below.
For general enquiries, contact SLS-PhDAdmin@dundee.ac.uk
