| Abstract |
Cystic fibrosis (CF) is the most common life-limiting inherited disease in the United Kingdom (UK). Over 9,000 people have CF and it affects around 1 in 2,500 newborn babies. CF is a chronic condition that is associated with significant medical problems that occur from an early age and may present at birth. Living with CF necessitates a daily burden of treatment, including oral medications, nebulisers, physiotherapy and a special diet, plus frequent clinic visits and prolonged hospital admissions. Progressive lung disease is the most important problem in CF and regularly leads to premature death in young adulthood. The median life expectancy for people with CF in the UK is 34 years. Although we know that CF is a condition that is inherited and involves problems with an ion channel in cells the exact cause of the lung disease is not fully understood. Current treatments do not cure patients, all of whom get progressive complications, most notably recurrent lung infections and inflammation leading to gradual loss of lung function and ultimately respiratory failure. Many patients require assessment for lung transplantation although this is not a viable option for everyone and there is a severe shortage of donor organs. A major problem with CF research is that it has traditionally been difficult to obtain highly relevant cells from inside the lungs of people with CF. My previous work performed during my PhD funded by a Medical Research Council (MRC) and CF Trust Training Fellowship identified a reliable way to do this by growing the cells directly from the diseased lungs removed when people with CF undergo lung transplantation at the Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne. I was also able to collect lung tissue for a research archive during this work. Recently researchers have found increased levels of a fat called 'ceramide' in lung tissue from a CF mouse model. This accumulation was associated with lung infection and inflammation - as we see in people with CF. In this current project I aim to use the valuable human CF cells and tissue to measure the levels of ceramide present. I will then investigate why ceramide may accumulate in CF cells, how it may cause lung inflammation and importantly a potential novel treatment to try and reduce ceramide levels. I will visit and collaborate with centres of excellence in Cambridge, Paris, Essen and New York to perform this work and will bring back knowledge and experience gained in these centres to further develop research in Newcastle. |
