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Preventing Infections

The prevention of infections theme of the CDT will focus on the development and testing of technologies that eliminate or reduce the presence of pathogens on surfaces, in air and in water.

EPSRC and BBSRC Centre for Doctoral Training in Engineering Solutions for Antimicrobial Resistance

Pathogens can persist on surfaces, in water and in air and can be transmitted from one host to another via these environments. Pathogens can also multiply and form biofilms on the surfaces of medical devices (e.g., catheters or implants), thereby causing severe infections, treatment failure and high costs to health services. The prevention of infections theme of the CDT will focus on the development and testing of technologies that eliminate or reduce the presence of pathogens on surfaces (both external and internal to the body), in water and in air.

To achieve this, we will deliver research training via, e.g., • studies on how infection-control practice and building design impact on the distribution and spread of AMR pathogens via surfaces, via water, heating and ventilation systems in healthcare environments; • novel technologies/materials for decontamination and (their use in) building design; • development and testing of novel surfaces with antimicrobial properties (e.g., antibiofouling) to use for medical devices, preventing biofilm formation and infection. 

Research Theme Contacts:

Richard Beckett & Lena Ciric

 

2025 Projects

Strategies to improve the antimicrobial properties of protein-based medical materials

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 display impressive mechanical properties, a hierarchical structure, dynamic responsiveness and environmental adaptability that are encoded in the amino acid sequence of their constituent proteins. Additionally, nature has also developed a broad range of short antimicrobial peptides (AMPs) or antimicrobial compounds (AMCs) that protect organisms from the attack from harmful microbes [2]. 

Inspired by this, scientists are increasingly using proteins to manufacture synthetic self-assembling materials with antimicrobial properties. Proteins are normally harvested from animal sources, but these sources suffer from batch-to-batch variability, presence of contaminants, and cultural or ethical concerns that limit their commercialisation potential. Fortunately, developments in recombinant DNA technology and bioprocess engineering allow us to biomanufacture non-animal-derived proteins. Furthermore, we can now explore protein sequences beyond those selected for by evolution [3-5]. This enables us to manufacture new protein-based multifunctional materials that combine the structural properties of Nature’s protein-based materials (e.g., the strength of silk, the stimuli-responsiveness of elastin, the stiffness of collagen) with the effectiveness of AMPs/AMCs. 

In this project, novel AMPs/AMCs will be identified from online databases or from in house metagenomes. You will then develop new antimicrobial materials by designing recombinant structural proteins that integrate selected AMPs/AMCs. These proteins will be produced via microbial fermentations or cell-free expression systems. Finally, you will synthesise protein films and test their mechanical, structural and antimicrobial properties. Specifically, the antimicrobial properties will be tested against gram negative and gram positive organisms such as B. subtilis and E. coli, as well as a number of clinically relevant ESKAPE pathogens such as S. aureus, P. aeruginosa and K. pneumonia. 

In this project, you will gain experience in metagenomics, recombinant biopolymer production and a range of materials synthesis and characterisation techniques. You will also be trained on standard methods for testing antimicrobial properties, such as zone of inhibition testing on agar plates and MIC testing in liquid culture. The project will be based at the Manufacturing Futures Lab (MFL) in UCL East, where the Lopez Barreiro and Jeffries research groups are based. MFL is a multidisciplinary 1500 m2 collaborative research space at the UCL East campus with a focus on knowledge-based manufacturing to deliver the sustainable products and processes of the future. Several groups at MFL are active in the area of AMR using different approaches, such as antimicrobial nanotopographies, or (bio)production of antimicrobial chemicals/biologicals… This will provide you with ample opportunities to network with other researchers active in the AMR field. You will also attend international conferences, publish the outcomes of the project, and interact with colleagues at UCL and beyond to disseminate your work.  

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 
 

Passive dynamic topographies for long-term infection prevention

Supervisors:

Martyna Michalska

Morgan Barnes

Project details:

Uncontrolled accumulation of microorganisms, especially ones with antibiotic-resistance, is becoming an immense societal challenge in which antifouling and antimicrobial surfaces are at the frontline. Recently, a new class of materials has emerged based on bioinspired nanopatterns [1-2], which repel or kill bacteria upon contact by imparting mechanical that should not induce AMR. Despite the effort to create synthetic analogues, their killing ability varies greatly across bacterial strains and is deemed short-lived due to accumulation of cellular debris. 

To address the issues, this PhD will develop dynamic topographies for long-term infection prevention using liquid crystal elastomers (LCEs) – a novel smart material capable of muscle-like actuation with stimuli-responsive reversible strains up to 100% [3]. Building on recent advances in static rigid mechano-bactericidal nanopatterns [1], and magnetically driven elastomers [4], we will employ the latest innovations in LCE manufacturing to create diverse micro/nano-topographies with dramatic shape changes to either repel, stretch bacterial envelope, and/or disturb and remove biofilms. This will also enable fundamental structure-property studies to probe how natural soft-solids achieve biofilm preventions/removal. We also hypothesise that such dynamic system will aid cellular debris removal and pattern self-healing, assuring sustainability of the approach. 

The first objective of the project will be to identify an optimal combination of pattern geometry-mechanical properties to achieve an antibacterial effect under static conditions (no flow, no actuation). The student will be introduced to various lithographic techniques (soft/nanoimprint etc.) to produce a range of materials as well as to antibacterial tests to evaluate their performance. Informed by the first task, various methods of patterning with LCEs of different composition will be employed probing the resolution limits and actuation strategies. Finally short- and long-term studies on antibacterial/antifouling efficiencies will be performed including dynamic tests under flow, followed by exploration of PICC lines (catheters), where the regular thermal fluctuations during usage will be exploited to actuate our LCE topographies for passive self-cleaning.  

During this project, the PhD student will develop skills in both materials development and studying the biointerface and antibacterial activity. The former includes polymer synthesis, smart materials, nano-engineering and nanomanufacturing, as well as material characterisation. The latter covers standard and elaborated antibacterial tests in collaboration with our NHS partner and methods to elucidate the killing pathways by means of biochemical assays and techniques such as fluorescence microscopy, electron microscopy, and flow cytometry.  

The student will be embedded in a multidisciplinary team across UCL and UCL Hospital (UCLH). The supervisory team includes  Dr. Martyna Michalska, an expert in  nanomanufacturing and mechano-bactericidal surfaces, and  Dr. Morgan Barnes, an expert in smart soft materials, who are from UCL’s Department of Mechanical Engineering. They are also members of the cutting-edge £15 million Manufacturing Futures Laboratory (MFL), which launched in 2023 and houses the state-of-the-art facilities for materials manufacturing and microbiological work. The PhD Student will primarily work in the MFL labs at UCL East in Olympic Park with occasional characterisation preformed at UCL’s central campus in Bloomsbury and UCLH under the supervision of Dr Shanom Ali (Director of 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  

Developing a standard testing methodology to detect droplet and aerosol generation from healthcare sanitaryware to support risk management for better infection prevention and control

Supervisors:

Lena Ciric

Elaine Cloutman-Green

Project details:

A cloud of droplets and aerosols is created every time a basin is used or a toilet flushed, carrying microorganisms which are then deposited on surfaces or linger in air posing an infection risk. These risks are recognised in healthcare guidance due to the presence of antibiotic-resistant pathogens and the vulnerable status of patients. The design of sanitaryware (e.g. shape, water flow rate and angle) impacts the quantity of droplets/aerosols generated, however neither manufacturers nor infection prevention and control (IPC) teams have a means by which to test this. Research in the area is sparse, outdated and inconsistent.1-5 A standard method is lacking to inform better design, manufacture, healthcare purchasing and IPC practice.  

This project aims to develop and validate a standardised quantification method for droplet/aerosol generation from sanitaryware to be used by manufacturers and within healthcare, through the following objectives:  

O1. In an environmental chamber, quantify droplet/aerosol generation in air and deposition on surfaces using: 

  • different handwash basin designs (various combinations of taps and basin shape) 
  • different toilet designs (various combinations of flush volumes, bowl shape and mechanics, presence of lid)  
  • a variety of quantification methods (e.g. viable microorganisms, surrogates, particle counters, etc.) 

O2. Assess the quantification methods from O1 for utility in field studies in healthcare and manufacturing premises 

O3. Using selected method(s) from O2, carry out testing at healthcare and manufacturing premises 

O4. Disseminate testing method to healthcare and manufacturing teams and assess usability through qualitative research methods.

The project will involve the use of microbial culture and molecular biology methods (e.g. qPCR, sequencing) to enumerate and identify microorganisms aerosolised through sanitaryware use. You will also use surrogates (e.g. fluorescent markers, DNA oligonucleotides) to monitor dispersal, and particle counters to quantify droplets/aerosols of different sizes. You will gain important insights into the design and manufacture of healthcare sanitaryware, and NHS purchasing and infection control guidance and policy. Through working with industry, the NHS and academia, you will gain important communication skills enabling you to achieve real impact with your research results.  

This project will develop a practical solution that will improve design and manufacture, NHS purchasing, IPC risk assessment and practice, and ultimately patient outcomes. We will disseminate the resulting test method through industry and healthcare, with the ultimate aim of having it imbedded in the NHS England Health Building Notes (HBN 00-01) and Health Technical Memoranda (HTM 04-01) which inform hospital design, building and maintenance.  

This project comes from an industry need identified by Ideal Standard, the UK’s biggest supplier of healthcare sanitaryware, who will be involved in project supervision. At UCL, you will join Prof Lena Ciric’s Healthy Infrastructure Research Group made up of seven researchers of diverse backgrounds and skill sets. Most of the work will take place in Prof Ciric’s BSL II laboratory including a walk-in environmental chamber. Prof Elaine Cloutman-Green is a Consultant Clinical Scientist and Infection Control Doctor at Great Ormond Street Hospital and will provide infection control expertise and access to NHS premises.  

References: 

1Schreck et al. (2021). Phys Fluids. 33.3. 2Kotay et al. (2019). Appl Environ Microb. 85: e01997-18. 3Yui et al. (2019). J Hosp InfectI. 103: e110-e114. 4Gerba et al. (1975). Appl Microb. 30: 229-237. 5Johnson et al. (2013). Am J Infect Control. 41: 254-258

 

Reduction of bacterial attachment to medical devices via mathematical modelling

Supervisors

Philip Pearce

Shervanthi Homer-Vanniasinkam

Project details:

In this PhD project, the student will collaborate with leading experts in mathematical modelling, clinical practice and biotech innovation to reduce bacterial attachment and colonisation of medical devices through mathematical modelling. 

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]. Bacteria that colonise implanted devices eventually form dense colonies known as biofilms that promote resistance to antibiotics [2]; these infections are extremely difficult to treat clinically. 

Mathematical modelling is a vital aspect of understanding how bacteria colonise medical devices – models allow us to generate testable experimental hypotheses, and eventually to improve device design to minimise colonisation. Existing models of bacterial attachment treat bacteria as passive particles in a flow [3]. However, bacterial swimming has recently been found to qualitatively alter attachment patterns [4]. It is not known how attachment links to specific swimming behaviours and surface interactions; this limits our ability to leverage the benefits of newly developed smart materials to minimise colonisation of medical devices. 

The aims of this PhD project are to: 

1) Develop experimentally validated cell-based and continuum models for attachment of bacteria to clinically relevant surfaces, including smart antimicrobial materials developed by Bonalive Biomaterials. 

2) Apply these models to optimise the design of medical devices to minimise bacterial attachment and infection in patients.  

Supervisors: Philip Pearce (lead supervisor), a UKRI Future Leaders Fellow, has significant experience of cell-based and continuum modelling of bacterial populations. Shervanthi Homer-Vanniasinkam (secondary supervisor) is a Consultant Vascular Surgeon at Leeds Teaching Hospitals NHS Trust, the Founding Professor of Surgery at the University of Warwick Medical School & University Hospitals Coventry and Warwickshire, and the first Professor of Engineering & Surgery at University College London. She will provide expertise in clinical relevance to medical devices and lead interactions with Bonalive Biomaterials (see Industrial Collaborators). Edwina Yeo (co-supervisor), a National Fellow in Fluid Dynamics, will provide experience in simulations and mathematical techniques for upscaling from microscale to macroscale models. Manish Tiwari (co-supervisor) will provide expertise in materials science and experimental validation of cell colonisation. 

Industrial Collaborators: Bonalive Biomaterials will provide unique smart biomaterials designed to inhibit bacterial growth, for testing models; the student may be able to visit Bonalive on an industrial placement later in the project. 

Methods: Simulations will be performed by building on existing code developed by cp-supervisor Edwina Yeo. Bayesian inference and optimisation to guide device design will use PyAdjoint for PDE optimisation. 

The student will integrate into PP’s research group at UCL Mathematics, a vibrant and highly diverse team that includes undergraduate/graduate students and postdoctoral researchers from various academic and cultural backgrounds. We run weekly group meetings for group members to present and receive feedback on work in progress, and wider Mathematical Biology Seminars with speakers from across the world presenting their research. Group members are active in promoting equality, diversity and inclusion within and outside the department. 

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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Novel ultrasound assisted antimicrobial strategies for dental biofilm infections

Supervisors:

Stavroula Balabani

Prof Panagiota Angeli

Project details:

Bacterial biofilms thrive in oral cavities and are the leading cause of most tooth and gum diseases. For example, one in two people worldwide is affected by endodontic disease (Tiburcio-Machado et al., 2021) caused by biofilms located in the root canal system.  If left untreated they can lead to dental caries, the most common noncommunicable disease worldwide (WHO.int, 2017). Antimicrobial resistance and the complex and confined environment of the oral cavity (e.g. root canal, dentinal tubules) makes eradicating oral infections challenging.  

To control oral bacterial infections and improve clinical outcomes new and more effective antimicrobial technologies are required. Ultrasonic instruments are commonly utilised in dentistry for biofilm removal. The physical processes induced by ultrasound (acoustic streaming and cavitation) can stimulate new antibiotic controlled drug release platforms, targeting localised biofilm infections and reaching difficult to access microscopic dental cavities.  

This studentship project aims to develop an ultrasound assisted antimicrobial nanoparticle technology for controlled drug release and localised biofilm removal from confined dental cavities such as dentinal tubules. To achieve this aim, the project will seek to: 

 a) engineer in vitro bacterial biofilm microenvironments mimicking oral cavities and dentine tubules,  

b) characterise the ultrasound assisted flow environment and drug particle transport therein and  

c) examine the controlled drug release mechanisms with a view to optimise particle characteristics and their stimuli response.  

The project  builds on from previous EPSRC Healthcare Technologies funded research (SONATA, EP/V028626/1) in collaboration with the University of Birmingham, Departments of Chemistry and Dentistry. It will leverage expertise from engineers, chemists, dentists and microbiologists to develop a novel targeted drug delivery platform  to eliminate oral bacteria,  transforming  the treatment of persistent dental infections and imprοving patient outcomes.  

The prospective student will join a vibrant research group environment with expertise in microfluidics,  complex and multiphase fluids, and  complex flows in biological and healthcare systems  across the scales (Flume, ThAMeS). The group is  equipped with state of the art flow diagnostics and characterisation facilities and also benefits from access to Manufacturing Futures Lab as well UCL Hawkes  Institute.  

The student will develop skills in microfabrication,  laser  based flow diagnostics, ultrasound induced flows , cell culturing as well as nanoparticle synthesis. They will have an opportunity to engage in truly interdisciplinary research and training working as part of a multidisciplinary  team to develop antimicrobial solutions.  There will be opportunities for secondments to collaborating labs in Birmingham (Chemistry, dentistry), as well as industry (e.g. Halyon-oral health and  BAM-materials, Germany) and collaboration with the UCL Eastman Dental Institute. 

Selected references 

Tibúrcio-Machado CS,  Michelon C,  Zanatta FB,  Gomes MS,  Marin JA,  Bier CA.  The global prevalence of apical periodontitis: a systematic review and meta-analysis. International Endodontic Journal,  54,  712–735, 2021. 

Koulogiannis, A., Walmsley, A.D., Angeli, P. et al. Ultrasonic irrigation flows in root canals: effects of ultrasound power and file insertion depth. Sci Rep 14, 5368 (2024). https://doi.org/10.1038/s41598-024-54611-x 

Van Der Sluis, L.W.M., Versluis, M., Wu, M.K. and Wesselink, P.R. (2007), Passive ultrasonic irrigation of the root canal: a review of the literature. International Endodontic Journal, 40: 415-426. https://doi.org/10.1111/j.1365-2591.2007.01243.x 

Boutsioukis, C.,  Arias-Moliz, M.T. &  Chávez de Paz, L.E. (2022)  A critical analysis of research methods and experimental models to study irrigants and irrigation systems. International Endodontic Journal,  55(Suppl. 2),  295–329. Available from: https://doi.org/10.1111/iej.13710 

Danielle S. W. Benoit , Kenneth R. Sims Jr., David Fraser, Nanoparticles for Oral Biofilm Treatments, ACS Nano 2019, 13, 5, 4869–4875 https://doi.org/10.1021/acsnano.9b02816 

Guo, J., Wang, P., Li, Y. et al. Advances in hybridized nanoarchitectures for improved oro-dental health. J Nanobiotechnol 22, 469 (2024). https://doi.org/10.1186/s12951-024-02680-5 

Thamires C. Miranda, Jayanaraian F.M. Andrade, Guilherme M. Gelfuso, Marcilio Cunha-Filho, Laudimar A. Oliveira, Tais Gratieri, Novel technologies to improve the treatment of endodontic microbial infections: Inputs from a drug delivery perspective, International Journal of Pharmaceutics, 635, 2023,122794, https://doi.org/10.1016/j.ijpharm.2023.122794 

Asier R. Muguruza, Maria L. Odyniec, Menisha Manhota, Zaina Habib, Knut Rurack, Jessica M.A. Blair, Sarah A. Kuehne, A. Damien Walmsley, Zoe Pikramenou, 

Antibiotic entrapment in antibacterial micelles as a novel strategy for the delivery of challenging antibiotics from silica nanoparticles, Microporous and Mesoporous Materials, 363,2024,112841, https://doi.org/10.1016/j.micromeso.2023.112841.