Preventing Infections

Starting in October 2026!

Supervisors: Manish Tiwari, Shervanthi Homer-Vanniasinkam

Overivew: Medical device-associated infections (MDAIs) are a major clinical and economic burden, particularly in orthopaedics where implant-related infections can lead to severe complications, including implant failure and limb amputation. Current antimicrobial coatings often rely on antibiotics or metallic agents, which may contribute to antimicrobial resistance (AMR) or cytotoxicity. This project aims to develop nanoengineered, slippery surface coatings that prevent bacterial adhesion and biofilm formation on orthopaedic implants without relying on antibiotics or toxic metals. By precisely tuning surface chemistry and nanoscale structure, these coatings will offer long-term, biocompatible protection against infection. The project will involve materials design, fabrication, characterisation, and biological testing, with clinical input from RNOH to ensure translational relevance

Approach and Methods: 

• Design and fabricate porous, nanoengineered surfaces with anti-adhesive, slippery properties
• Characterise surface morphology, chemistry, and mechanical durability
• Conduct biological assays to assess bacterial adhesion, biofilm formation, and cytocompatibility
• Collaborate with RNOH for clinical insight, testing platforms, and regulatory guidance Evaluate long-term performance and potential for clinical translation 

Impact and Outlook: This project addresses a critical unmet need in orthopaedic surgery by developing infection-resistant implant coatings that do not contribute to AMR. The technology has the potential to reduce infection rates, improve implant longevity, and lower healthcare costs. The approach may also be extended to other medical devices, supporting 

Starting in October 2026!

Supervisors: Dr. Michele Crotti, Dr. Martyna Michalska

Overview: Biofilm-associated infections account for nearly 80% of human microbial infections and are notoriously resistant to antibiotics and disinfectants. With antimicrobial resistance (AMR) on the rise, there is an urgent need for non-antibiotic strategies to prevent and control biofilm formation on medical devices. This PhD project proposes a novel approach: integrating mechanical and enzymatic antibiofilm mechanisms into medical-grade polymers to create next-generation single-use medical consumables with built-in, robust antibiofilm properties. By combining micro/nanopatterned surfaces with immobilised enzymes that degrade biofilms and disrupt microbial communication, the project aims to overcome the limitations of each individual strategy and deliver synergistic, resistance-proof infection prevention technologies.

Approach and Methods:

• Select, clone, and purify a library of antibiofilm enzymes (e.g., quorum-quenching oxidoreductases, acylases, lactonases).
• Design and fabricate patterned surfaces optimised for enzyme immobilisation.
• Assess synergistic antibiofilm efficacy under static and dynamic (flow-based) biofilm models.
• Apply advanced microscopy, protein engineering, and nanofabrication techniques.
• Test materials against clinically relevant pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus.

Impact and Outlook: This project will deliver a new class of hybrid antimicrobial materials with potential for real-world application in healthcare settings. By addressing the limitations of current antibiofilm strategies, the research could lead to safer, more effective medical devices and reduce reliance on antibiotics, contributing to global AMR mitigation efforts.

Starting in October 2026!

Supervisors: Duygu Dikicioglu, Eli Keshavarz-Moore 

Overview: Antifungal resistance is a growing and under-recognised global health threat. Fungal infections affect over a billion people annually, with life-threatening consequences for immunocompromised individuals. With few antifungal drugs available and resistance on the rise, this project explores a novel strategy: engineering the fungal microenvironment to weaken resistance mechanisms and enhance the efficacy of existing treatments. By manipulating stress responses in fungi such as Saccharomyces cerevisiae and Aspergillus nidulans, the project aims to “trick” resistant strains into becoming drug-sensitive. This interdisciplinary research combines synthetic biology, molecular biology, and biochemical engineering to pioneer sustainable, non-pharmacological antifungal therapies.

Approach and Methods:

• Develop and optimise laboratory models of fungal growth and resistance.
• Investigate how environmental stress factors (e.g. osmotic and nutrient stress) alter resistance mechanisms.
• Use high-throughput screening and biofilm models to identify conditions that reduce multidrug resistance (MDR).
• Build a systems-level understanding of how these mechanisms could be applied in biotechnology, healthcare, and environmental contexts.
• Employ synthetic and molecular biology tools to design and test new methods of controlling fungal behaviour.

Impact and Outlook: This project aims to pioneer a sustainable approach to combating antifungal resistance by enhancing the effectiveness of existing treatments. The findings could inform the development of innovative, non-pharmacological therapies and have broad applications in healthcare, biotechnology, and environmental microbiology.

Starting in October 2026!

Supervisors: Maximilian Besenhard and Maryam Parhizkar

Overview: Antimicrobial peptides (AMPs) are natural molecules produced by the immune system and represent one of the most promising avenues for developing new treatments against drug-resistant infections. Their rapid action and ability to target bacteria in several ways make it difficult for antimicrobial resistance to emerge. Despite this promise, AMPs have proven challenging to turn into effective medicines, as they are fragile, easily broken down, and prone to losing their activity before reaching the site of infection.

Encapsulating AMPs within nanoparticles can protect them and help deliver them precisely where they are needed. However, designing suitable AMP-nanoparticle combinations is complicated. Many formulation ingredients, concentration ratios, and processing conditions influence their behaviour, creating a vast and complex landscape that traditional experimentation cannot navigate efficiently.

This project addresses this challenge by bringing together I) microfluidic/flow-based nanoparticle synthesis, which underpins modern nanoparticle drug delivery systems including the Pfizer–BioNTech COVID-19 vaccine, together with II) high-throughput experimentation via laboratory automation and III) AI navigation of the complex landscape described.

This powerful combination not only supports the creation of AMP based nanomedicines, but also addresses a central challenge in modern medicine: many promising drugs lack effective delivery systems. Hence, this project not only allows the student to make a real-world impact, but also provides, through our strong network of industry and healthcare partners, a rare opportunity to develop a highly sought-after interdisciplinary skill set that is in demand across both academia and industry. 

Approach and Methods:

• Formulate model antimicrobial peptides using microfluidic flow reactors
  Using our established microfluidic nanoprecipitation platforms, the student will learn to formulate key AMPs such as LL-37, Melittin, and Temporin B into polymeric and lipid nanoparticles. This flow-based approach is widely used in modern nanomedicine development and provides precise, scalable control over nanoparticle synthesis.
• Automate synthesis and characterisation using robotics
  By integrating automated microfluidic reactors with our robotic systems for sample handling and analysis, the student will work with a platform that performs nanoparticle synthesis and characterisation autonomously. This setup enables fast, reproducible, and high-throughput experimentation while giving the student hands-on experience with state-of-the-art automation.
• Generate rich, large-scale formulation datasets to leverage AI technologies
  Using this automated platform, the student will produce hundreds to thousands of AMP-nanoparticle formulations. Each experiment will capture key variables such as formulation components, process conditions, particle size, stability, loading efficiency, and antimicrobial activity, creating a dataset suitable for data-driven optimisation.
• Apply user-friendly AI tools for data analysis and guided optimisation
  The student will apply, not develop, AI methods using easy-to-use platforms such as AMLearn®. These tools will help identify correlations, determine the most influential formulation parameters, and guide iterative optimisation decisions.
• Evaluate biological performance of optimised formulations
  The student will test the most promising formulations for antimicrobial activity, stability, and functionality to identify candidates with strong therapeutic potential.
   

Impact and Outlook: The integration of flow-based nanoparticle formulation, high-throughput automation, and AI-guided optimisation creates a powerful platform with impact far beyond AMP nanomedicines. These technologies address one of the most persistent challenges in modern drug development as many promising therapeutics lack suitable delivery systems. By providing a blueprint for accelerated and systematic formulation, this approach can support a wide spectrum of emerging treatments, including cancer immunotherapies, nucleic acid-based medicines (not only vaccines), and other complex biological therapeutics.

The project also offers substantial long-term value in training the next generation of researchers. Working across chemical engineering and the School of Pharmacy, and engaging directly with industrial and healthcare partners, the student will develop a rare interdisciplinary skill set that spans nanoparticle design, flow chemistry, automation, and applied AI. Such a combination is increasingly sought after in modern pharma and biotech environments, where digital, data-driven, and autonomous approaches are rapidly reshaping research and manufacturing. This training will therefore equip the student with a flexible and competitive career profile, opening pathways in academia and industry such as pharmaceutical R&D, and other emerging technology sectors. Together, these impacts support the development of new medicines while providing lasting benefits for the student’s career.

 

Starting in October 2026!

Supervisors: Darren Nesbeth and Eli Keshavarz-Moore

Overview: Horizontal gene transfer via conjugative plasmids is a major but underexploited driver of antimicrobial resistance (AMR) spread. These mobile genetic elements autonomously transfer between bacteria, disseminating resistance genes across microbial populations. Recent advances have demonstrated the potential of “counter-plasmids” that can propagate through bacterial communities while deactivating AMR genes. However, current designs are limited by scalability and complexity. This project aims to overcome these limitations by integrating large language model (LLM)-based genome design tools with bioprocess engineering to create next-generation therapeutic conjugative plasmids. These engineered plasmids will be optimised for industrial-scale production and capable of suppressing AMR gene dissemination in clinical and environmental settings

Approach and Methods:

• Synthetic biology: Construct modular conjugative plasmids with engineered payloads targeting AMR gene suppression
• AI-driven genome design: Use LLM tools (e.g. PlasmidGPT, Evo2) to refactor plasmid genomes for enhanced manufacturability, safety, and performance
• Microbial validation: Test plasmid efficacy against WHO-priority AMR gene analogues in relevant bacterial hosts
• Bioprocess optimisation: Develop high-cell-density cultivation protocols in bioreactors, addressing plasmid stability, host stress, and yield bottlenecks
• Data-driven design iteration: Integrate empirical data to refine AI-generated plasmid designs

Impact and Outlook: This project will deliver scalable, deployable countermeasures against AMR by engineering conjugative plasmids that can suppress resistance gene spread. Mid-term applications include GMP-grade oral formulations as adjuncts to antibiotic therapies. Long-term, environmental deployment could mitigate AMR in agriculture and wastewater systems. The integration of AI with synthetic biology and bioprocess engineering represents a transformative approach to tackling AMR at scale

Student: 

Lillian Wang

Supervisors

Diego Lopez Barreiro 

Jack Jeffries

Project details:

Nature has evolved structural protein biopolymers that self-assemble into complex and functional materials such as bone, collagen fibres, or silk webs [1]. These materials exhibit impressive mechanical properties, hierarchical structure, dynamic responsiveness, and environmental adaptability — all encoded in the amino acid sequences of their constituent proteins. Nature has also developed a wide range of short antimicrobial peptides (AMPs) and antimicrobial compounds (AMCs) that protect organisms from microbial threats [2].

Inspired by these natural systems, this project is developing synthetic self-assembling protein-based materials with antimicrobial properties. Traditional protein sources, often animal-derived, pose challenges including batch variability, contamination risks, and ethical concerns. Advances in recombinant DNA technology and bioprocess engineering now allow for the biomanufacture of non-animal-derived proteins and the exploration of novel sequences beyond those selected by evolution [3–5].

The team is identifying AMPs and AMCs from online databases and in-house metagenomic datasets. These are being integrated into recombinant structural proteins designed to combine the mechanical properties of natural biopolymers (e.g. silk’s strength, elastin’s responsiveness, collagen’s stiffness) with antimicrobial functionality. Proteins are being produced via microbial fermentation and cell-free expression systems.

Current work involves synthesising protein films and characterising their mechanical, structural, and antimicrobial properties. Antimicrobial testing includes assays against gram-negative and gram-positive organisms such as Bacillus subtilis and Escherichia coli, as well as clinically relevant ESKAPE pathogens including Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae.

The project is based at the Manufacturing Futures Lab (MFL) at UCL East, home to the Lopez Barreiro and Jeffries research groups. MFL is a 1500 m² multidisciplinary space focused on sustainable, knowledge-based manufacturing. The lab hosts several AMR-focused groups working on approaches such as antimicrobial nanotopographies and bioproduction of antimicrobial agents, offering rich opportunities for collaboration and knowledge exchange.

Researchers involved in the project are gaining hands-on experience in metagenomics, recombinant biopolymer production, materials synthesis, and antimicrobial testing techniques including zone of inhibition and MIC assays. Dissemination activities include conference presentations, publications, and engagement with the wider UCL and AMR research communities.

References: 

[1] YJ Yang, AL Holmberg, BD Olsen, Artificially Engineered Protein Polymers, Annu Rev Chem Biomol Eng, 8, 549–575, 2017. https://doi.org/10.1146/annurev-chembioeng-060816-101620 

[2] M Magana, The value of antimicrobial peptides in the age of resistance. Lancet Infect. Dis. 20, e216–e230, 2020. https://doi.org/10.1016/s1473-3099(20)30327-3 

[3] E Shire, AAB Coimbra, C Barba-Ostria, L Rios-Solis, D López Barreiro, Molecular design of protein-based materials – state of the art, opportunities and challenges at the interface between materials engineering and synthetic biology, Mol Syst Des Eng, 2024. https://doi.org/10.1039/D4ME00122B 

[4] D López Barreiro, A Folch-Fortuny, I Muntz, JC Thies, CMJ Sagt, GH Koenderink, Sequence Control of the Self-Assembly of Elastin-Like Polypeptides into Hydrogels with Bespoke Viscoelastic and Structural Properties, Biomacromolecules, 24, 489–501, 2023. https://doi.org/10.1021/acs.biomac.2c01405 

[5] A da Costa, R Machado, A Ribeiro, T Collins, V Thiagarajan, MT Neves-Petersen, JC Rodríguez-Cabello, AC Gomes, M Casal, Development of Elastin-Like Recombinamer Films with Antimicrobial Activity, Biomacromolecules, 16, 625-635, 2015. https://doi.org/10.1021/bm5016706 
 

Student:

Kisa Fatima

Supervisors:

Martyna Michalska

Morgan Barnes

Project details:

Uncontrolled microbial accumulation, especially of antibiotic-resistant strains, remains a major societal challenge. Antifouling and antimicrobial surfaces are a key line of defence. Recently, bioinspired nanopatterned surfaces have emerged that kill or repel bacteria through mechanical interactions without promoting antimicrobial resistance [1, 2]. However, synthetic analogues often show variable efficacy across strains and lose effectiveness over time due to cellular debris buildup.

To address these limitations, this project is developing dynamic topographies for long-term infection prevention using liquid crystal elastomers (LCEs), smart materials capable of muscle-like actuation with reversible strains up to 100 percent [3]. Building on advances in static mechano-bactericidal surfaces [1] and magnetically driven elastomers [4], the team is creating micro and nano-topographies that can dramatically change shape to repel bacteria, stretch cell envelopes, disrupt biofilms, and remove debris. This approach also enables fundamental studies into how soft solids in nature prevent or remove biofilms.

The first phase of the project focused on identifying optimal pattern geometries and mechanical properties for antibacterial effects under static conditions. Lithographic techniques such as soft and nanoimprint lithography were used to fabricate test surfaces, which were evaluated using antibacterial assays. Based on these findings, the team is now developing LCE-based surfaces with varied compositions and actuation strategies, probing resolution limits and dynamic performance.

Short and long-term antibacterial and antifouling tests are underway, including dynamic flow experiments. The project is also exploring applications in peripherally inserted central catheters (PICC lines), leveraging thermal fluctuations during use to trigger passive self-cleaning via LCE actuation.

Researchers are gaining expertise in polymer synthesis, smart materials, nanoengineering, and material characterisation, alongside advanced biointerface studies. Antibacterial testing is conducted in collaboration with NHS partners, using biochemical assays, fluorescence and electron microscopy, and flow cytometry to investigate bacterial killing mechanisms.

The project is embedded within a multidisciplinary team across UCL and UCL Hospital (UCLH). Supervision is provided by Dr Martyna Michalska, an expert in nanomanufacturing and mechano-bactericidal surfaces, and Dr Morgan Barnes, an expert in smart soft materials, both from UCL Mechanical Engineering and members of the £15 million Manufacturing Futures Laboratory (MFL). The PhD student is primarily based at MFL in UCL East, with additional characterisation work at UCL Bloomsbury and UCLH under Dr Shanom Ali, Director of the UCLH Environmental Research Laboratory.

[1] Michalska M. et al. Adv Mater 2021, 33, 2102175 Link 

[2] Michalska M. et al. Nanoscale, 2018,10, 6639 Link 

[3] Barnes M. et al. Soft Matter, 2019, 15, 870 Link 

[4] Gu H. et al. Nat Commun 2020, 11, 2211 Link  

Student

Maria-Otilia Casuneanu

Supervisors

Philip Pearce

Shervanthi Homer-Vanniasinkam

Project details:

This PhD project brings together experts in mathematical modelling, clinical practice, and biotech innovation to reduce bacterial attachment and colonisation of medical devices through advanced modelling approaches.

Bacterial infections in implanted medical devices such as catheters, arterial stents, and bone grafts account for nearly half of all healthcare-associated infections and cost the NHS an estimated £1 billion per year [1]. Once bacteria colonise these devices, they form dense biofilms that promote resistance to antibiotics [2], making infections extremely difficult to treat.

Mathematical modelling plays a vital role in understanding how bacteria colonise medical devices. Models help generate testable experimental hypotheses and guide improvements in device design to minimise colonisation. Existing models often treat bacteria as passive particles in flow [3], but recent findings show that bacterial swimming can significantly alter attachment patterns [4]. The link between swimming behaviours, surface interactions, and attachment remains unclear, limiting our ability to optimise smart materials for infection prevention.

The project is currently focused on developing experimentally validated cell-based and continuum models for bacterial attachment to clinically relevant surfaces, including smart antimicrobial materials provided by Bonalive Biomaterials. These models are being applied to optimise medical device design with the goal of reducing bacterial attachment and infection risk in patients.

The supervisory team includes Philip Pearce, a UKRI Future Leaders Fellow with expertise in modelling bacterial populations. Shervanthi Homer-Vanniasinkam, a Consultant Vascular Surgeon and Professor of Engineering and Surgery at UCL, provides clinical insight and leads collaboration with Bonalive Biomaterials. Edwina Yeo, a National Fellow in Fluid Dynamics, contributes expertise in simulation and mathematical upscaling. Manish Tiwari supports the project with materials science and experimental validation.

Bonalive Biomaterials is providing smart biomaterials designed to inhibit bacterial growth for model testing. The student may have the opportunity to visit Bonalive on an industrial placement later in the project.

Simulations are being developed using existing code from co-supervisor Edwina Yeo. Bayesian inference and optimisation techniques are being applied using PyAdjoint for partial differential equation optimisation to guide device design.

References: [1] VanEpps & Younger. "Implantable device-related infection." Shock, 2016. [2] Savage V.J., et al. Staphylococcus aureus biofilms promote horizontal transfer of antibiotic resistance. Antimicrob. Agents Chemother. 2013. [3] Bull et al., “Urine production rate is critical in a model for catheter-associated urinary tract infection” bioRxiv, 2022. [4] Secchi, et al. “The effect of flow on swimming bacteria controls the initial colonization of curved surfaces” Nat. Comm., 2020 

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