Over the last two decades it has become clear that multiple diseases such as lung infections in people with cystic fibrosis are caused by a community of microorganisms (the microbiota), rather than a single pathogen in isolation. These polymicrobial communities
may interact to maintain health, but in the case of cystic fibrosis lung infections drive antimicrobial resistance and disease. This PhD will challenge the dogma of working with one microorganism in isolation in terms of understanding antimicrobial resistance and virulence. We now have the molecular genomic and next-generation sequencing tools to tease apart complex interactions in microbiology.
The overall aim of the research will be to build an integrated molecular understanding of how microbial communities interact to maintain health or drive antimicrobial resistance and disease.
The student will carry out the following objectives:
OBJECTIVE 1. UNDERSTAND HOW SIMPLE MIXED COMMUNITIES INTERACT IN WIDELY USED LABORATORY MODELS.
By mixing a dominant pathogen such as Pseudomonas with a secondary microbiota member such as Candida, we have shown that behaviour in assays such as bacterial motility, biofilm formation, antimicrobial susceptibility, and virulence factor production (eg. lipases and proteases), alter dramatically. Using well characterised panels of resistant pathogens and microbiota, the student will interact them in pairs, and expand this to diverse polymicrobial communities depending on outcomes which drive resistance or disease.
OBJECTIVE 2. MOLECULAR UNRAVELLING OF POLYMICROBIAL INTERACTIONS WHICH MEDIATE GREATER 4 / 15 ANTIMICROBIAL RESISTANCE AND VIRULENCE.
Combinations of dominant and secondary microbiota producing novel interactions such as increased biofilm formation or antimicrobial resistance will be studied in molecular detail. Transcriptomics (RNA-sequencing), proteomics and metabolite production will be used to identify the genomic pathways that facilitate the increases in virulence or antimicrobial resistance within the polymicrobial interaction.
OBJECTIVE 3. DEVELOPING MIXED MODELS OF ANTIMICROBIAL SUSCEPTIBILITY TESTING.
Only a single pathogen in isolation is tested in clinical laboratories to determine which antibiotics should be given for an infection. The outcome of these tests are not useful for treating polymicrobial CF lung infections. Student will use the “mixed” modelling experience from above, in combination with the latest microbiota analysis tools to develop new polymicrobial susceptibility testing assays, ultimately applying these to CF sputum. This will determine if particular antibiotics or combinations of antibiotics perform better on different communities driving antimicrobial resistance.
This studentship is available to UK and EU nationals who have established UK residency (EU nationals must have ordinarily lived in the UK throughout the three years preceding the start of the studentship). Please refer to the DTP eligibility webpage for more details: https://www.swbio.ac.uk/programme/eligibility/
Cardiff University will be able to award up to one fully funded four-year studentship for EU students who do not meet the residency requirements.
Please refer to the DTP eligibility webpage for academic entry requirements: https://www.swbio.ac.uk/programme/eligibility/
If English is not your first language, you will need to achieve an IELTS score of 6.5 with 6.5 in all skills.
How to apply
Make your application to Cardiff University: https://www.cardiff.ac.uk/study/postgraduate/applying/how-to-apply
Please ensure that your application includes:
Two references. Neither of the referees should be part of the supervisory team.
Academic transcripts / degree certificate(s)
Personal statement. Please include supporting evidence for your Maths background.
Curriculum Vitae (CV)
English language certificates (where applicable)
Please refer to the DTP webpage for information about the selection process: https://www.swbio.ac.uk/programme/selection-process/
Applications must be submitted by midnight on Monday 2nd December 2019.