Delivery Strategies in Phage Therapy: Balancing Host Responses and Th

Description

Cystic fibrosis (CF) is the most common inherited genetic condition in the UK, affecting over 11,000 individuals. For people with CF (pwCF), protecting lung health throughout their lives is essential. Recent modulator therapies have brought significant improvements in quality of life for many with the condition. Nevertheless, chronic, drug-resistant respiratory infections remain a serious issue for pwCF across all age groups, and some people cannot use modulators.

Respiratory infections are a primary cause of illness and death in CF, with antibiotics widely used to manage these infections. However, over time, the efficacy of these drugs is diminished by growing antimicrobial resistance (AMR), as well as increasing toxicity and side effects. For some pwCF, treatment options are severely limited or even unavailable. This problem is part of a broader trend of rising global AMR, reducing effective therapeutic choices. The development pipeline for new antimicrobials is limited, even for priority pathogens identified by the World Health Organization, such as Pseudomonas aeruginosa. The TRAILFINDER innovation hub is focused on translational innovation and is funded by the CF Trust and LifeArc as 1 of 4 hubs in the UK. The TRAILFINDER hub will address key challenges relevant to pwCF including access to the novel treatment, phage therapy.

Bacteriophage (or phage) therapy is considered safe¹ and has the flexibility to be tailored for a range of bacterial species. For pwCF, phage therapy has been successfully applied to manage, and in some cases, resolve chronic lung infections^2-4. Despite these successes, case studies are still limited, and although the clinical trial results are encouraging, there is still limited guidance on best practices. Additionally, little is known about optimising routes of delivery and the potential variations in host responses.

Whilst certain routes such as nebulisation may be preferable to reduce treatment burden, little is known about the impact of delivery route on phage efficacy against respiratory infection. Building on our existing published data⁵, we will seek to administer phage by preferred routes if possible, however other routes may show greater efficacy. Furthermore, therapeutic phage application leads to direct contact between phage and eukaryotic cells. Phage can cross epithelial barriers, suggesting the possibility of penetration into unintended tissues and interaction with immune cells. This exciting project will investigate these interactions using a suite of validated and experimental assays.

This PhD student will join a vibrant lab at the University of Liverpool and be part of a cohort of students, many funded by the TRAILFINDER Hub. We are committed to fostering PhD students in all aspects of development and training. The student will be based within the Dept of Clinical Infection, Microbiology and Immunology and will get the opportunity to collaborate with the wider Hub including researchers at the University of Manchester and UKHSA. Shortlisted applicants will get the opportunity to visit the laboratories and meet the wider group.

Applications should be made to Prof Aras Kadioglu (ak68@liv.ac.uk) and include a CV and cover letter with the subject heading “Phage PhD Application”. Candidates should have a degree in a relevant Life Sciences discipline and outline any experience that makes them the ideal candidate for the position. The applications deadline is 25/11/24.