Answering questions about lung inflammation in CF to design future treatments

Lung inflammation remains a major concern for everyone with CF. However, we need better and more specific anti-inflammatory treatments. Led by Professor Robert Gray at the University of Glasgow, researchers within the DEFINE-CF Strategic Research Centre (SRC) programme will apply cutting-edge new techniques, alongside existing methods of analysis to find and test possible new ways to treat inflammation.

Summary of the research

Cystic fibrosis (CF) lung disease is characterised by repeated cycles of infection and inflammation that cause lung damage. CF modulator drugs have improved the lives of many people living with CF. But airway infection and inflammation persist and remain a concern for everyone with CF.

Anti-inflammatory treatments are an important part of managing lung health in people with CF, alongside treatments for infections. However, we need better and more specific anti-inflammatory treatments. To develop these treatments, we need a better understanding of when inflammation occurs and what happens when it does. With this new information, treatments can be more precisely designed and developed. 

During inflammation, a range of chemical messengers co-ordinate reactions within the cells that line the lungs and the actions of many different immune (defence) cells. The way inflammation is currently detected and monitored provides ‘circumstantial evidence’ – such as changes to immune cells and levels of chemicals in the blood – rather than direct evidence of what happens in inflammation. 

New techniques mean that it is now possible to study lung inflammation from a different perspective and more directly. Researchers within this SRC programme will apply these new techniques, alongside existing methods of analysis, to find and test possible new chemicals or proteins to ‘target’ and treat inflammation. 

For example, the CFTR protein is a ‘target’ for medicines such as Kaftrio, where the medicine improves how the protein works. Sometimes medicines work by stopping or reducing how their ‘target’ works.

By the end of the SRC programme, the researchers hope to have identified new targets for anti-inflammatory medicines that can be used in the future to develop new medicines.

An explanation of the research in more detail is given below:

  • Work package 1 Collecting samples for research

    Researchers will collect bronchoscopy samples from people with CF and from healthy controls, as well as collect blood samples from participants at the same time. They will also have access to lung tissue removed during lung transplant through a Newcastle University biobank.

  • Work package 2 Analysing the samples using spatial biology techniques

    An innovative technique called spatial biology will be used to analyse the new samples and re-analyse stored samples.

    They will study whether inflammation in the lungs of people with CF on modulators is different to inflammation in those who are not taking these medicines. They will also investigate whether inflammation is different in the lungs of people with CF in comparison to the lungs of people who don’t have CF.

  • Work package 3 Analysing the same samples using proteomic and metabolomic analysis

    Using the same samples, researchers will analyse the different proteins present during inflammation (the collective name for a group of proteins is a proteome) and also analyse the smaller chemicals that work alongside the proteins (the metabolome). This analysis will take place at the University of Indiana. Researchers in Indiana will also develop software to allow the analysis of all three sets of data together (ie the spatial biology together with the proteomics and metabolomics).

  • Work package 4 Refining possible drug targets using other methods

    Colleagues in Newcastle, Leeds and Glasgow will investigate whether specific proteins in different types of immune cells could be targeted as a potential treatment for lung cell inflammation, based on results from earlier work packages. Studies will be performed in the presence and absence of modulators, to understand whether these approaches could work for everyone.

Who is involved?

Principal investigator

Professor Robert Gray, University of Glasgow

 

Co-investigators

Professor Nigel Jamieson, University of Glasgow 
Dr Nicola Robinson, University of Glasgow 
Dr Malcolm Brodlie, University of Newcastle
Dr Iram Haq, University of Newcastle 
Professor Daniel Peckham, University of Leeds 
Professor James Chmiel, Indiana University, US
Prof Gang Bao, Rice University, US

Thank you

Thank you to Mr and Mrs Reid for their generous legacy towards the cost of the DEFINE-CF SRC programme, given in loving memory of their sons Stuart and Scott who both had CF.