Overview
Chronic lung infections caused by Pseudomonas aeruginosa are a defining feature of diseases such as cystic fibrosis and bronchiectasis. These infections are notoriously difficult to treat due to biofilm formation, high bacterial densities, and the rapid evolution of antimicrobial resistance, all of which severely limit the effectiveness of conventional antibiotics. There is an urgent need for alternative antimicrobial strategies that are effective under clinically realistic conditions.
About this opportunity
Bacteriophage (phage) therapy is a promising alternative, offering targeted antibacterial activity and the potential to overcome antibiotic resistance. However, despite strong laboratory evidence, clinical translation has been slow. Key barriers include challenges in delivery, dosing, and achieving predictable efficacy in complex biological environments. In particular, most phage studies assume high-dose, immediate exposure—conditions that rarely reflect real clinical use.
This PhD project addresses these challenges by focusing on how bacteriophages perform when delivered using long-acting drug delivery technologies. Dissolvable microneedle patches, a rapidly developing platform in long-acting therapeutics, offer a potential route to sustained systemic exposure while improving patient adherence. For phages, however, such delivery routes impose non-traditional biological constraints, including drying and encapsulation stresses, delayed and repeated low-dose exposure, and transport through tissue- and blood-like environments before reaching the lung. How phages survive, move, and retain efficacy under these constraints remains poorly understood.
The overall aim of this project is to understand and engineer bacteriophage survival, transport, and antibacterial efficacy under long-acting, transdermal-style delivery constraints relevant to chronic P. aeruginosa lung infection. Using P. aeruginosa and its phages as a model system, the project combines laboratory microbiology, biofilm biology, and microbial bioengineering.
The research will progress through four interconnected aims. First, the student will determine how microneedle-relevant formulation stresses—such as drying, polymer encapsulation, and rehydration—affect phage survival and infectivity. Second, phage transport and persistence will be quantified using in vitro skin-to-blood mimicking systems that model the journey from the delivery site to systemic circulation. Third, phage–bacteria infection dynamics will be defined under delivery-imposed constraints, including low multiplicity of infection, delayed exposure, and repeated low-dose dosing designed to mimic sequential patch application. Finally, based on identified limitations such as resistance emergence or poor low-dose performance, phages will be engineered to improve robustness, host range, or resistance suppression, and benchmarked directly against natural phages.
The project offers extensive interdisciplinary training across microbiology, biofilms, phage biology, in vitro delivery models, and phage engineering, supported by a multidisciplinary supervisory team and strong national collaborations. The student will also benefit from interactions with major funded programmes in phage therapy and long-acting therapeutics, including Trailfinder-CF, HALO and SafePhage, as well as opportunities for collaborative research and training at partners at Queen’s University Belfast and the University of Manchester.
This PhD will generate foundational knowledge required to translate phage therapy into long-acting delivery formats and directly addresses a major barrier in antimicrobial innovation. It is ideally suited to candidates with a strong interest in microbiology, antimicrobial resistance, and translational biomedical engineering.