2025-26 Project (Lindsay & Knight)

Antimicrobial Resistance (AMR) gene transfer in Methicillin Resistant Staphylococcus aureus (MRSA): mechanisms and dynamics using clinical isolates

SUPERVISORY TEAM

Supervisor

Professor Jodi Lindsay at City St George’s
Email: jlindsay@sgul.ac.uk

Co-Supervisor

Dr Gwen Knight at LSHTM
Email: Gwen.Knight@lshtm.ac.uk

PROJECT SUMMARY

Project Summary

Antimicrobial resistance (AMR) is a growing global problem that requires innovative, cross-disciplinary solutions. Despite this, the genetic mechanisms and dynamics that underpin the transfer and stability of resistance genes within bacterial population are poorly understood.  In this project, we will use clinical strains of methicillin resistant Staphyloccocus aureus (MRSA), the most important global AMR pathogen, to measure and then characterise the genetic components behind gene transfer of resistance. 

Paired with bioinformatic analysis, and mathematical modelling, this project will have direct translational impact on clinical practice and will inform our understanding of the underlying evolutionary drivers and how these can be optimally harnessed for AMR control.

Project Key Words

Antimicrobial resistance, MRSA, evolution, mathematical modelling

MRC LID Themes

  1. Infectious Disease
  2. Translational and Implementation Research
  3. Global Health
  4. Health Data Science

Skills

MRC Core Skills

  1. Whole organism physiology
  2. Interdisciplinary skills
  3. Quantitative skills

Skills we expect a student to develop/acquire whilst pursuing this project

Antimicrobial resistance, microbiology, mathematical modelling

Routes

Which route/s are available with this project?

  • 1+4 = Yes
  • +4 = Yes

Possible Master’s programme options identified by supervisory team for 1+4 applicants:

  • City St George’s – MRes Biomedical Science – Antimicrobial Resistance
  • City St George’s – MRes Biomedical Science – Infection and Immunity
  • LSHTM – MSc Medical Microbiology

Full-time/Part-time Study

Is this project available for full-time study? Yes
Is this project available for part-time study? Yes

Location & Travel

Students funded through MRC LID are expected to work on site at their primary institution, meeting – at the minimum – the institutional research degree regulations and expectations. Students may also be required to travel for conferences (up to 3 over the duration of the studentship), and for any required training (for research degree study). Other travel expectations and opportunities highlighted by the supervisory team are noted below.

Primary location for duration of this research degree: City St George’s, London

Travel requirements for this project: Opportunities to attend and present at national and international conferences.

Eligibility/Requirements

Particular prior educational requirements for a student undertaking this project

  • Minimum City St George’s institutional eligibility criteria for doctoral study.
  • Good undergraduate degree in biological sciences with laboratory experience.
  • Post-graduate research degree in microbiology, genetics or a quantitative field may be an advantage.

Other useful information

  • Potential Industrial CASE (iCASE) conversion? = No

PROJECT IN MORE DETAIL

Scientific description of this research project

MRSA is the most common cause of AMR death, and affects all branches of human medicine. In this project we will use microbiology and mathematical modelling techniques to investigate how clinical isolates exchange AMR genes, leading to infections that are harder to prevent and treat.

MRSA resistance genes are often carried on mobile genetic elements and transfer using endogenous bacteriophage.  We have built laboratory and mathematical models of transfer, incorporating antimicrobial exposure and using  epidemiologically successful MRSA isolates. The dynamics of gene exchange are complex, but tractable, and improving our understanding of the drivers and barriers to AMR gene exchange and how they can be manipulated in evolving  MRSA populations will lead to better targeted interventions. 

Project objectives 
– Using newly discovered genes demonstrated to be involved in MRSA gene transfer, determine their distribution and role in gene transfer in a collection of  epidemiologically successful vs unsuccessful MRSA 
– Investigate environmental conditions or external interventions that control AMR gene transfer in clinical isolates 
– Model how genes and environmental interventions may contribute to AMR spread in MRSA populations. 

Techniques to be used 
– Microbiology laboratory assays of AMR gene transfer, including confirmation using molecular methods 
– Microbial bioinformatics 
– Mathematical modelling, building on established models. 

Resources 
All of the methods, equipment and materials for this project are currently available in our laboratory. This project is  building on a series of successful MRC-LID DTP projects and an experienced team of supervisors, collaborators and  externally funded projects. 
– MRSA laboratory with all assays and resources for studying and characterising resistance available at St George’s as well as data from past experiments 
– A comprehensive set of clinical MRSA isolates from the UK and Europe are already available and characterised with  WGS. 
– Mathematical modelling framework, with training and support available within CMMID at LSHTM  New MRC grant award will see a new post-doc and RA start in the lab in early 2025 for 3 years.

Further reading

Relevant preprints and/or open access articles:
(DOI = Digital Object Identifier)

Additional pre-application materials:

  • The strain collection we will use is here  10.1016/j.cmi.2023.05.015

Additional information from the supervisory team

The supervisory team has provided a recording for prospective applicants who are interested in their project. This recording should be watched before any discussions begin with the supervisory team.

Lindsay-Knight recording

MRC LID LINKS

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