Developing CRISPR-Cas antimicrobials to tackle antibiotic resistance spread in Klebsiella pneumoniae. MRC GW4 BioMed DTP PhD studentship for 2026/27 Entry, Department of Ecology and Conservation (Penryn) Ref: 5624

Supervisors

Lead Supervisor:  Professor Stineke van Houte - University of Exeter - Faculty of Environment, Science and Economy

Co-Supervisors:

Dr David Sünderhauf - University of Exeter - Faculty of Environment, Science and Economy

Professor Ed Feil - University of Bath

The GW4 BioMed2 MRC DTP is offering up to 17 funded studentships across a range of biomedical disciplines, with a start date of October 2026.

These four-year studentships provide funding for fees and stipend at the rate set by the UK Research Councils, as well as other research training and support costs, and are available to UK and International students.

About the GW4 BioMed2 Doctoral Training Partnership

The partnership brings together the Universities of Bath, Bristol, Cardiff (lead) and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities, with opportunities to participate in interdisciplinary and 'team science'. The DTP already has over 90 studentships over 6 cohorts in its first phase, along with 80 students over 4 cohorts in its second phase.

The 122 projects available for application, are aligned to the following themes;

• Infection, Immunity, Antimicrobial Resistance and Repair

• Neuroscience and Mental Health

• Population Health Sciences

Applications open on 1 September 2025 and close at 5.00pm on 20th October 2025.

Please note that we may close the application process before the stated deadline if an unprecedented number of applications are received– check our website for details.

Studentships will be 4 years full time. Part time study may also be available.

Project Information

Research Theme:  Infection, Immunity & Antimicrobial Repair

Summary:

Antimicrobial resistance (AMR) poses a major threat to human health, which is for a large part driven by plasmids (mobile pieces of DNA) that facilitate AMR gene spread between bacteria. In this project you will develop new tools based on CRISPR-Cas to stop the spread of AMR- carrying plasmids in the important pathogen Klebsiella pneumoniae. 

Proof-of-concept work shows that this is theoretically possible, but challenges remain in discerning drivers of plasmid competition. This interdisciplinary project integrates microbiology, genomics, and synthetic biology to tackle one of the most urgent challenges in infectious disease, providing training in leading-edge approaches with real-world impact. 

Description:

Widespread antibiotic use has made modern healthcare possible, and treatment of bacterial infections accessible and cheap. However, recent decades have seen a rise of antimicrobial resistant (AMR) bacterial infections which cannot be treated by conventional means, and finding a solution to this AMR crisis is urgently needed. Bacteria frequently take up AMR genes through a process called horizontal gene transfer – the transfer of genetic material between bacterial strains and species.

Mobile genetic elements such as plasmids are an important vector of AMR genes, and these are particularly relevant to the opportunistic human pathogen Klebsiella pneumoniae and close relatives. K. pneumoniae has a particular propensity to cause hospital- or community-acquired AMR infections including pneumonia, urinary tract, and bloodstream infections. Extended-spectrum-beta-lactamase- producing and carbapenem-resistant K. pneumoniae infections account for nearly 100,000 infections and >7000 deaths annually within Europe. Mobile genetic elements are abundant in environmental and clinical strains of K. pneumoniae and often carry clinically relevant genes, including virulence factors and AMR. Beyond being an opportunistic pathogen of humans, K. pneumoniae is also associated with plants, animals, and the environment. K. pneumoniae is known to capture AMR genes and plasmids from environmental bacteria and act as a conduit to pass these elements on into other human pathogens, thus building a link between environmental reservoirs of AMR and the clinic through plasmid transfer.

The fact that many AMR genes are carried by plasmids provides an opportunity to control their spread: bacteria have evolved a wide range of defence systems to selectively associate with mobile genetic elements. A well-known example of this is the CRISPR-Cas defence system. Many defences are themselves carried by mobile genetic elements, including plasmids – and it is hypothesized such mobile defences are important in competition between plasmids. Recently, we have shown that the effectivity of CRISPR-Cas carried by a plasmid is determined by the mobility of the plasmid, and that the strength of

CRISPR-Cas can influence the outcome of competition between plasmids (Sünderhauf et al. 2025 bioRxiv). Furthermore, we have been able to harness the ability of CRISPR-Cas to specifically cleave a sequence in order to target AMR genes carried by plasmids, which allows us to resensitise pathogens to make them susceptible to antibiotics (Sünderhauf et al. 2023 Microbiology).

The successful candidate will use a collection of human-associated K. pneumoniae isolates collected in clinical settings and from the wider community in Thailand and Italy to identify the role that plasmid- encoded microbial defences such as CRISPR-Cas play in plasmid competition, and how other competitive plasmid genes can modulate this interaction. By first describing which plasmids, resistance genes, and virulence genes are most commonly found amongst diverse K. pneumoniae isolates, the project will aim to develop a CRISPR-Cas9- based technology to stop their transfer. Plasmid transfer rates from human-associated K. pneumoniae isolates into laboratory strains, and between isogenic K. pneumoniae and E. coli strain backgrounds will be measured (objective 1). These data will be considered in the context of the presence of relevant plasmid-borne genes, including AMR, virulence, microbial defences, counter-defences, and other genes which may influence the plasmids’ competitive ability. Having identified targets for a CRISPR-Cas AMR resensitisation treatment, molecular cloning techniques will be used to generate CRISPR-Cas plasmids which can target and remove K. pneumoniae AMR plasmids (objective 2). Finally, plasmid competition experiments will be carried out with natural and fluorescently labelled plasmids to identify whether plasmid genes involved in competition are more effective when static or mobile, and to discover under which conditions a CRISPR-Cas plasmid can outcompete K. pneumoniae AMR and virulence plasmids and thus prevent their transfer (objective 3).

The successful applicant will take an active role in developing new bioengineering approaches to remove AMR genes from clinically relevant bacterial strains, and provide helpful insights to discern which plasmid genes influence the outcome of plasmid competition. We are excited to work with a student who is willing and able to take ownership of the project, and steer the direction based on data generated within earlier objectives. K. pneumoniae isolates carry many diverse plasmids and other mobile genetic elements with many types of AMR, virulence, and defence genes, and the student will be encouraged to choose their own focus within the second part of their PhD.

The student will be based at the Cornwall campus of the University of Exeter, within the Environment and Sustainability Institute under the supervision of Prof Stineke van Houte and Dr David Sünderhauf. They will work closely with members of the van Houte group of all career stages and will be part of the Penryn Microbiology Early Career Researcher network at the University of Exeter (~ 100 members).

Bioinformatic aspects of the PhD will be supervised by Prof Ed Feil at the Milner centre at the University of Bath and can be carried out remotely or during research visits to Bath.

Funding

This studentship is funded through GW4BioMed2 MRC Doctoral Training Partnership. It consists of UK tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£20.20780 p.a. for 2025/26, updated each year).

Additional research training and support funding of up to £5,000 per annum is also available.

Eligibility

Residency:

The GW4 BioMed2 MRC DTP studentships are available to UK and International applicants. Following Brexit, the UKRI now classifies EU students as international unless they have rights under the EU Settlement Scheme. The GW4 partners have agreed to cover the difference in costs between home and international tuition fees. This means that international candidates will not be expected to cover this cost and will be fully funded but need to be aware that they will be required to cover the cost of their student visa, healthcare surcharge and other costs of moving to the UK to do a PhD.  All studentships will be competitively awarded and there is a limit to the number of International students that we can accept into our programme (up to 30% cap across our partners per annum).

Academic criteria:

Applicants for a studentship must have obtained, or be about to obtain, a first or upper second-class UK honours degree, or the equivalent qualification gained outside the UK, in an appropriate area of medical sciences, computing, mathematics or the physical sciences.  Applicants with a lower second class will only be considered if they also have a Master’s degree. Please check the entry requirements of the home institution for each project of interest before completing an application. Academic qualifications are considered alongside significant relevant non-academic experience.

English requirements:

If English is not your first language you will need to meet the English language requirements for the University of Exeter by the start of the programme. Please refer to the details in the following web page for further information https://www.exeter.ac.uk/study/englishlanguagerequirements/

Please check the relevant English Language requirements of the university that will host the PhD project.  

Data Protection

If you are applying for a place on a collaborative programme of doctoral training provided by Cardiff University and other universities, research organisations and/or partners please be aware that your personal data will be used and disclosed for the purposes set out below.

Your personal data will always be processed in accordance with the General Data Protection Regulations of 2018. Cardiff University (“University”) will remain a data controller for the personal data it holds, and other universities, research organisations and/or partners (“HEIs”) may also become data controllers for the relevant personal data they receive as a result of their participation in the collaborative programme of doctoral training (“Programme”).

Further Information

For an overview of the MRC GW4 BioMed programme please see the website www.gw4biomed.ac.uk

Entry requirements

Academic Requirements

Applicants for a studentship must have obtained, or be about to obtain, a first or upper second-class UK honours degree, or the equivalent qualification gained outside the UK, in an appropriate area of medical sciences, computing, mathematics or the physical sciences. Applicants with a lower second class will only be considered if they also have a Master’s degree. Please check the entry requirements of the home institution for each project of interest before completing an application. Academic qualifications are considered alongside significant relevant non-academic experience.

English Language Requirements

If English is not your first language you will need to meet the English language requirements for the University of Exeter by the start of the programme. Please refer to the relevant university website for further information.  This will be at least 6.5 in IELTS or an acceptable equivalent.  Please refer to the English Language requirements web page for further information.

Please check the relevant English Language requirements of the university that will host the PhD project. 

How to apply

A list of all the projects and how to apply is available on the DTP’s website at gw4biomed.ac.uk.  You may apply for up to 2 projects and submit one application per candidate only.

Please complete an application to the GW4 BioMed2 MRC DTP for an ‘offer of funding’.  If successful, you will also need to make an application for an 'offer to study' to your chosen institution.

Please complete the online application form linked from our website by 5.00pm on Monday, 20th October 2025.  Please note that we may close the application process before the stated deadline if an unprecedented number of applications are received– check the DTP’s website for details and updates

If you are shortlisted for interview, you will be notified from Tuesday, 23rd December 2025.  Interviews will be held virtually on 27th and 28th January 2026.  

Further Information

For informal enquiries, please contact GW4BioMed@cardiff.ac.uk

For project related queries, please contact the respective supervisors listed on the project descriptions on our website.

Summary