About the Project
Microorganisms grow as biofilms on surfaces, from teeth to surgical implants or even the lining of the lungs. Biofilms are dense cell aggregates embedded in a complex matrix of molecules that surrounds and protect the cells. Critically, this matrix confers resistance to antimicrobial treatments with both chemical (e.g. antibiotics) and physical (e.g. acidic/basic conditions, detergents) mechanisms of action, with the matrix eventually sacrificing only the external layers, leaving the underlying…
microbes unharmed. Complex carbohydrates have long been recognised as key components of the biofilm matrix and therefore viable targets for therapeutic strategies to combat biofilm formation. However, such approaches have been hindered by the fact that these carbohydrates are traditionally difficult to recognise and bind, meaning that they effectively provide a shielding effect similar to the glycan coverage of viruses. In this project, we will address this issue by leveraging our expertise in the design of proteins that can bind specific carbohydrates to effectively hijack the protective biofilm matrix and use it to facilitate delivery of agents that will trigger biofilm matrix degradation and improve access by antimicrobial treatments.
To deliver this proof-of-concept project, three major bacterial pathogens have been selected for which biofilm formation is a key virulence factor: Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus mutans. P. aeruginosa and S. aureus are also high priority pathogens on the World Health Organization 2024 list because of their global threat due to antimicrobial resistance (AMR). P. aeruginosa is notorious for causing chronic lung infections in immunocompromised individuals, patients suffering from burn wounds or cystic fibrosis patients. It produces three distinct extracellular polysaccharides (EPS): Psl, Pel, alginate. Psl is a neutral repeating pentameric saccharide built up from D-mannose, L-rhamnose and D-glucose. Pel is a cationic linear homopolymer of partially de-N-acetylated α-1,4-GalNAc built up from predominantly dimeric repeats of α-1,4-linked galactosamine and N-acetylgalactosamine. Alginate is an anionic polymer composed of β-1,4linked D-mannuronic and α-L-guluronic acids on which the C-2 and C-3 hydroxy groups of the mannuronic acid residues can be acetylated to a varying degree. S. aureus is responsible for a range of conditions, including bacteraemia, infective endocarditis, osteomyelitis, and skin and soft tissue infections. Its predominant EPS is partially deacetylated poly-β-1,6-N-acetylglucosamine (dPNAG). S. mutans is a leading cause of dental caries, a global disease that affects 3.1 billion people worldwide, with major impacts on quality of life. Its key biofilm constituent is a polymer of α-1,3-linked glucose, with an increase in 3-linked branch points (e.g. 2,3-, 3,4-, 3,6- and 3,4,6-linked glucose) when formed on a surface.
The project will proceed through the following objectives:
- Analysis of designability for targets. Student will explore available literature and investigate the structural characteristics of candidate EPS to identify the requirements for protein design and to prioritise the targets.
- Computationally design novel protein carbohydrate-binding domains. Student will learn and further develop physics-based and machine-learning tools in molecular docking, structure prediction and protein design (e.g. Autodock Vina, Rosetta, RFdiffusion).
- Selection of binders. Student will subject the pool of designed proteins to selection processes (e.g. yeast display) to identify binding candidates.
- Expression and characterisation of selected clones. Student will express the selected clones in Escherichia coli, purify and biophysically characterise the proteins, and assess binding to carbohydrates in vitro via fluorescence polarisation and isothermal titration calorimetry.
- Binding to biofilms. Student will use established biofilms models for each bacterium and assess binding of the designer proteins labeled with fluorophores.
- Biofilm degradation. Proteins that display the most effective binding will be fused with exo- and endo-glucanases and these fusion proteins then tested for their capacity to degrade carbohydrate and disrupt bacterial biofilms.
- Improved antimicrobial activity. Fusion proteins will be applied to bacterial biofilms in combination with existing antimicrobial treatments (e.g. antibiotics) to assess if the fusion proteins can enhance antimicrobial penetration into the biofilms and thus improve biofilm sensitivity.
Eligibility
Residency: GW4 BioMed3 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 will be required to personally 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.
English requirements: If English is not your first language you will need to meet the English language requirements by the start of the programme. Link
How to Apply
A list of all the projects and how to apply is available on the GW4 BioMed website at gw4biomed.ac.uk. You may select up to 2 projects and submit one application per candidate only.
Please complete an application to the GW4 BioMed3 for an ‘offer of funding’. If successful, you will also need to make an application for an 'offer to study' to your chosen institution later.
Please complete the online application form linked from our website by 5.00pm on Wednesday, 21st October 2026. Please note that we may close the application process before the stated deadline if an unprecedented number of applications are received– check the GW4 BioMed website for details and updates.
If you are shortlisted for interview, you will be notified from Tuesday, 22nd December 2026. Interviews will be held virtually on 26th and 27th January 2027. Studentships will start on 1st October 2027.
For informal enquiries, please contact GW4BioMed@cardiff.ac.uk
For project related queries, please contact the respective supervisors listed on the project descriptions on the GW4 BioMed website.
Funding Notes
These studentships are funded through GW4 BioMed3 MRC Doctoral Landscape Programme and consist of UK tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£21, 805 p.a. for 2026/27, updated each year).
Additional research training and support funding of up to £5,000 per annum is also available.
GW4 BioMed3 studentships are available to UK and International applicants
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