Skip to Content

CF-LID (Cystic Fibrosis - Lung infection Discovery) Study– ‘Lifting the LID’ on respiratory pathogens in patients with Cystic Fibrosis

School of Medicine, Dentistry and Biomedical Sciences | PHD

Applications are now CLOSED
Funding
Funded
Reference Number
SMED-2241-1009
Application Deadline
14 February 2024
Start Date
1 October 2024

Overview

Cystic Fibrosis (CF) is a lung disease caused by a defective gene, affecting over 10,000 people in the UK. In people with CF, the lungs become clogged with thick mucous that results in chronic infection and inflammation, causing lung damage. Therefore, it is vital to detect which pathogens (e.g. bacteria) are causing infection in the lungs, so that the correct treatment can be given. To do this, usually mucous (sputum) coughed up from the lungs is tested using microbial culture. However, important new medications to treat CF, called cystic fibrosis transmembrane conductance regulator modulators reduce the amount of sputum a person with CF produces. In addition, some people with CF, especially children, are unable to cough up sputum. In these people, it is very difficult to detect lung pathogens, making it harder to adequately treat any infection present, which may lead to lung damage. The CF-LID (Cystic Fibrosis Lung infection Discovery) study aims to develop and test novel ways of detecting lung pathogens independent of traditional sputum culture methods. This project will develop assay techniques for detecting genetic material of lung pathogens in blood and in other types of respiratory samples as an alternative to testing in sputum.

As detailed in the project overview, there is urgent unmet need to establish new methods for detecting lung pathogens in patients with CF. This project will build on established links between research teams in Belfast and international researchers in Canada to develop novel culture-independent assays for pathogen detection in lung infections in CF.

The project will begin with a comprehensive literature review to identify existing culture-independent techniques for lung pathogen identification. Next the project will aim to use Delphi Survey methodology to reach a consensus list of priority lung pathogens to detect in people with CF. Given the importance of antimicrobial resistance (AMR) in treatment of lung infections, a consensus list of priorities for AMR detection will also be developed. As part of this Delphi survey, the research team in Belfast will arrange consensus meetings based on the team’s existing connections, with the aim of including patient representatives, CF healthcare clinicians and researchers across the UK and Europe. Based on the consensus list developed by the Delphi survey, molecular assays will be then developed to detect listed pathogens in both blood and non-sputum respiratory samples as detailed below.

Blood sample analysis: Liquid biopsy is a new approach developed from cancer diagnosis work that utilises next-generation sequencing (NGS) of cell-free DNA (cfDNA) from distant cells recovered in the blood. cfDNA has also been identified as a potential means of diagnosing infectious diseases, including to identify pathogens in patients with CF. In this project, protocols for molecular detection of cfDNA in blood, initially designed from simulated specimens, will be optimised by testing on clinical samples from both children and adults with CF. Methods to improve diagnostic yield will be explored as part of the molecular assay development in available clinical samples. The developed assays will also be evaluated in blood samples from children with lung infection who do not have CF to determine the potential validity of detecting pathogens in non-CF lung infections as well.

Alternative respiratory sample analysis: NGS detection assays will be developed for use in alternative respiratory samples such as, for example, cough swabs, breath analysis and near-source breath testing. Assay performance will be determined by testing of clinical samples from both paediatric and adult patients with CF.

Additional project opportunities: This project presents an exciting opportunity to investigate a very important area of research need for people with CF. Throughout the project, there will also be opportunity to interact with CF clinicians and patients, to build connections with local and international researchers, and to present work at national and international conferences.

Second Supervisor: Dr Deirdre Gilpin. Tertiary Supervisor: Damian Downey

Funding Information

Funded by the Department for the Economy (DfE). For UK domiciled students the value of an award includes the cost of approved tuition fees and maintenance support the 2024/25 rates are still to be confirmed (current rates for 2023/24 are Fees £4,712, Stipend £18,622). To be considered eligible you must have been ordinarily resident in the UK for the full 3-year period prior to the start of the studentship and you must be ordinarily resident in Northern Ireland on the first day of the start of the studentship. For further information about eligibility criteria please refer to the DfE Postgraduate Studentship Terms and Conditions at https://www.economy-ni.gov.uk/publications/student-finance-postgraduate-studentships-terms-and-conditions

Project Summary
Supervisor

Dr Helen Groves

Research Profile

Mode of Study

Full-time: 3 Years

Funding Body
DfE This project will also be supported by fundi
Apply now Register your interest