Funded MSc: Exploring target site blockers as a novel therapeutic strategy for rare cystic fibrosis mutations

• Principal investigator(s) Dr Chiara De Santi, Petra Bencurova
• Research theme Respiratory Medicine

CF is a genetic disease caused by mutations in the CFTR gene. While highly effective treatments are now available for many people with CF, some patients with rare mutations still have limited therapeutic options and continue to have an unmet clinical need.

The approach is based on target site blockers (TSBs), a type of nucleic acid therapy that interferes with microRNAs, natural regulators of gene expression. Previous studies from the group showed that TSBs can increase CFTR expression and function in other forms of cystic fibrosis, but their potential in rare CF mutations remains largely unexplored.

During this two-year, full-time MSc, you will use a range of advanced human cellular models, including gene-edited airway epithelial cells and induced pluripotent stem cell (iPSC)-derived airway organoids, to investigate whether TSBs can enhance the effects of existing and experimental CF therapies.

The main aim of the project is to determine whether a novel microRNA-targeting approach can increase CFTR protein expression and improve CFTR function in laboratory models of cystic fibrosis carrying rare disease-causing mutations.

This project offers the opportunity to work at the interface of molecular biology, RNA therapeutics and respiratory medicine. You will gain hands-on experience in a broad range of contemporary research techniques, including cell culture, organoid models, gene expression analysis, microscopy, protein analysis and functional assays.

You will also learn how potential therapies are evaluated in preclinical models and how laboratory discoveries can inform future treatment strategies. The project is particularly suited to students interested in translational biomedical research, as it combines fundamental questions about gene regulation with practical approaches to addressing an important challenge in cystic fibrosis research.

This research project is funded by Vertex Pharmaceuticals.

Key objectives

• Characterise the expression of CFTR-regulating microRNAs in cellular models of rare CF mutations.
• Test combinations of TSBs with approved and experimental CF therapies to identify the most promising treatment strategy.
• Evaluate the effects of these treatments on CFTR protein expression and function in advanced airway cell and organoid models.

Tenure: Two years

Start date: January 2027

Specification

Minimum requirements

• Lower second class (2.2) honours degree (or equivalent) in biomedical sciences, molecular biology, genetics, cellular biology, physiology, biotechnology or similar.
• English language requirement is IELTS 6.5–7.0 or equivalent.

Desirable candidate specifications

• Strong background in molecular biology, cell biology, genetics, or a related discipline.
• Demonstrated interest in experimental laboratory research and willingness to learn new techniques.
• Previous experience in mammalian cell culture, gene expression analysis, western blot or microscopy is desirable.
• Good interpersonal skills and a strong collaborative spirit.
• Excellent organisational and communication skills

Application process

Please apply for the research project through the link below.