PhD Internship in Lethal Zygosis, AMR Plasmids and Bacterial Defence

Project: Mechanism and Consequences of Lethal Zygosis in Bacteria Restricting AMR Plasmids Supervisors: Dr Tatiana Dimitriu and Prof M.

F. White

The University of St Andrews is inviting applications for a funded PhD project investigating how bacterial defence systems influence the spread of antimicrobial resistance (AMR).

Antimicrobial resistance is one of the major challenges facing modern medicine. A significant proportion of AMR genes are carried on conjugative plasmids, mobile DNA elements that can move between bacteria and help resistance traits spread through bacterial populations.

This PhD will investigate an intriguing consequence of bacterial defence against these plasmids: lethal zygosis.

Lethal zygosis occurs when bacteria that are unable to successfully accept a conjugative plasmid become damaged or die as a result of repeated plasmid transfer attempts. Understanding this process could provide new insights into how bacterial defence systems shape AMR transmission and bacterial competition.

The project will also examine how these interactions influence phage infection and phage therapy, making the research relevant to both antimicrobial resistance and bacteriophage biology.

The successful PhD candidate will investigate three main areas:

The research will examine how lethal zygosis occurs and how its effectiveness changes depending on the characteristics of the AMR plasmid and the bacterial defence system involved.

The project will investigate lethal zygosis across a collection of environmental and clinical

E. coli strains to understand how widespread and variable this phenomenon is.

The candidate will study how lethal zygosis affects plasmid transmission and bacterial susceptibility to phage infection. This could provide valuable insights into the relationship between bacterial defence systems, AMR plasmids and phage therapy.

The successful candidate will:

• Design and carry out experiments in molecular and evolutionary microbiology.
• Investigate bacterial defence systems and AMR plasmid interactions.
• Study the mechanisms underlying lethal zygosis.
• Work with clinical and environmental
  
  E. coli strains.
• Perform bacterial genetics and mutant construction.
• Use molecular biology techniques to investigate plasmid and bacterial interactions.
• Apply flow cytometry and microscopy to analyse bacterial responses.
• Investigate interactions between plasmid transmission and phage infection.
• Analyse and interpret experimental data.
• Present research findings through scientific presentations, reports and publications.
• Participate in the interdisciplinary training offered through the EASTBIO Doctoral Training Partnership.
• Complete a three-month placement in a non-academic organisation.

Depending on their interests, the successful candidate may also have opportunities to develop skills in bioinformatics, mathematical modelling and experimental evolution.

Applicants should have, or expect to obtain, a strong degree in a relevant subject such as:

• Microbiology
• Molecular Biology
• Biotechnology
• Genetics
• Biomedical Sciences
• Biological Sciences
• A related discipline

The ideal candidate will have:

• A strong interest in microbiology, bacterial genetics and antimicrobial resistance.
• An interest in molecular mechanisms underlying bacterial adaptation and defence.
• Good laboratory and experimental skills, or a willingness to develop them.
• An ability to analyse scientific data critically.
• Good written and verbal communication skills.
• The ability to work independently as well as collaboratively within a research team.
• Enthusiasm for interdisciplinary research.

Previous experience in bacterial genetics, molecular microbiology, plasmid biology, phage biology, bioinformatics or experimental evolution would be advantageous.

The PhD will be based primarily within the Biomedical Sciences Research Complex at the University of St Andrews and will be supervised by Dr Tatiana Dimitriu.

The successful candidate will become part of the EASTBIO Doctoral Training Partnership, providing access to interdisciplinary training, a wider doctoral research community and professional development opportunities.

The program also includes a three-month non-academic placement, giving the student an opportunity to gain experience outside the university…