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Genome scale evolution of biofilm contained Klebsiella pneumoniae in response to sub-lethal antibacterial stress exposure - development of novel biomarkers for near-patient testing

Project Description

Project details:

Klebsiella pneumoniae is an opportunistic pathogenic bacterium found in several niches, being often encountered in a biofilm. Infections in at risk populations can result in substantial morbidity and mortality. A mortality rate of around 50% is not uncommon, even with chemotherapeutic intervention. The latter feature may in part be accounted for by the fact that in a biofilm bacterial metabolism slows.

When subjected to sub-inhibitory stresses, K. pneumoniae will respond and evolve. Mutations can include single nucleotide polymorphisms (SNPs), as well as the acquisition of mobile genetic elements (MGE), and these can provide a genetic history that can be exploited for therapeutic purposes. Characterisation of these genes/biomarkers by whole genome sequencing (WGS) offers the prospect of developing precision diagnostic tools that may benefit public health by reducing the risk of therapeutic failure.

Evolutionary studies have rarely been applied to biofilm models due to a lack of validated methods that simulate the adaption in response to stressors in vivo.

This project will - i) develop an in vitro glass bead-based model to study genome scale changes in K. pneumoniae underpinning evolution and adaptation during biofilm development over time in both the presence/absence of sub-inhibitory chemical stressors (including antibacterial agents, biocides and salinity gradients) - ii) characterisation of the observed phenotypes - iii) describe the bacterial transcriptome using RNA-seq - iv) validate a subset of biomarkers using nanopore capture of probe guided DNA duplexes containing SNPs with simultaneous quantification of the mutated bacterial population.

Findings can be translated to provide for near-patient testing in clinical real-time via precision diagnostic tools.

This project will be supervised by Professor Seamus Fanning of Queen’s University School of Biological Sciences/Institute for Global Food Security and Professor Brendan Gilmore of Queen’s University School of Pharmacy/Institute for Global Food Security.

All applications MUST be submitted through https://dap.qub.ac.uk/portal/user/u_login.php.

Specific skills/experience required by applicants:

Any prospective student would need to have a good background in microbiology (or other related discipline) along with some molecular biology laboratory skills, including whole genome sequencing and basic bioinformatics.

All applicants must meet the academic entry requirements: https://www.qub.ac.uk/courses/postgraduate-research/biological-sciences-phd.html#entry

Funding Notes

Only UK and EU students are eligible to apply. Before applying, it is strongly recommended that you read the full information on eligibility criteria available from DfE: View Website.

Please note in particular that not all successful applicants may be eligible to receive a full studentship (i.e. fees and stipend) - please read in detail the Residency and Citizenship requirements in the document linked to above.

How good is research at Queen’s University Belfast in Agriculture, Veterinary and Food Science?

FTE Category A staff submitted: 33.40

Research output data provided by the Research Excellence Framework (REF)

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