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BBSRC SWBio DTP Studentship: Antimicrobial resistance mechanisms in the presence of sub-inhibitory antibiotics and the microbiome


Cardiff School of Biosciences

About the Project

BACKGROUND.
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 with themselves and with therapeutic antibiotics, but in most polymicrobial diseases end up driving 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. It will harness molecular genomic and next-generation sequencing tools to tease apart the complex interactions that occur between pathogens, microbiota and antibiotics. AIM. The overall aim of the research will be to build an integrated molecular understanding of how microbial communities interact to 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), altered 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 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.

ELIGIBILITY
Applicants for a studentship must have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science or technology. Applicants with a Lower Second Class degree will be considered if they also have a Master’s degree or have significant relevant non-academic experience.

In addition, due to the strong mathematical component of the taught course in the first year and the quantitative emphasis in our projects, a minimum of a grade B in A-level Maths or an equivalent qualification or experience is required.

Applicants must ensure they highlight their Maths background within their application and to upload any supporting evidence.

Funding Notes

A fully-funded four year SWBio DTP studentship will cover:
• a stipend* (at the standard UKRI rate; £15,285 per annum for 2020-2021)
• research and training costs
• tuition fees (at the standard UKRI rate)
• additional funds to support fieldwork, conferences and a 3-month placement


References

HOW TO APPLY
This studentship has a start date of October 2021. In order to be considered you must submit a formal application via Cardiff University’s online application service. (To access the application system, click the 'Visit Institution' button on this advert) 
There is a box at the top right of the page labelled ‘Apply’, please ensure you select the correct ‘Qualification’ (Doctor of Philosophy), the correct ‘Mode of Study’ (Full Time) and the correct ‘Start Date’ (October 2021). This will take you to the application portal. 
In order to be considered candidates must submit the following information: 
• Supporting statement 
• CV 
• Qualification certificates 
• Proof of English language (if applicable)
• In the research proposal section of the application, please specify the project title and supervisors of the project and copy the project description in the text box provided. In the funding section, select “I will be applying for a scholarship/grant” and specify advertised funding from BBSRC SWBio DTP. If you are applying for more than one Cardiff University project, please note this in the research proposal section as the form only allows you to enter one title.

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