Spatial transcriptomics of lung tissue (IRAS 324567)

Persistent lung infections are a major challenge for people with cystic fibrosis because the bacteria can survive treatment for many years. We want to understand how these bacteria interact with the body's cells and avoid being cleared by the immune system or antibiotics. By analysing donated lung tissue using advanced techniques that measure gene activity in both human cells and bacteria, we hope to uncover how these infections become established and persist. Our findings could help guide the development of better treatments for chronic lung infections in cystic fibrosis.

People with cystic fibrosis are highly susceptible to chronic bacterial lung infections, many of which are resistant to treatment and can persist for decades. We aim to improve understanding of the interactions between human cells and disease-causing bacteria that enable these infections to survive and evade treatment.

We will analyse retrospectively collected lung tissue from transplant recipients using spatial transcriptomics to examine gene expression in both human cells and bacterial pathogens. Tissue samples obtained from the Duke University tissue bank will undergo DNA and RNA extraction and sequencing at the Wellcome Sanger Institute. The study uses existing donated tissue samples only and involves no participant interventions or identifiable patient information.

Rationale

Cystic Fibrosis (CF) is a life-limiting disease that causes infections and inflammation in the airways and lungs, which affects 10,000 people in the UK alone. In recent years, therapies have been introduced that lengthen and improve the quality of life of people with CF by correcting a misformed protein. Despite this, there are certain pathogens that still remain a significant issue within CF and in other lung diseases. The longevity of these pathogens in patients enables them to form drug resistance or evade treatments.

This research will give a rare insight into host-pathogen interactions within patients and will be the first of its kind to apply new spatial transcriptomics. This work will look at both host cell type and microbial diversity to see what links there are between host-pathogen interactions and different pathways of disease progression, which could lead to new therapies for CF.

Aims

The study aims to identify novel host-pathogen interactions in the context of chronic lung disease which will lead to the development of new therapies.

Primary Outcome

Identification of human RNA transcripts that are differentially expressed between uninfected and infected parts of tissue

Key Secondary outcome(s)

Identification of bacterial RNA transcripts that are differentially expressed in different parts of the lung from the same individual.

Study Type

Observational

Participant and Sample Information

Populations involved:

Individuals with Cystic Fibrosis.

Countries of recruitment:

International

Approximate participant or sample numbers (if applicable):

10

Key inclusion criteria:

• Samples that been have donated to Duke University.
• Samples from adult male and female patients with cystic fibrosis at the time of lung transplantation.
• Samples from individuals who previously had respiratory colonisation with M. abscessus or P. aeruginosa.

Key exclusion criteria:

Samples which do not meet the criteria above.

Recruitment status:

Non-recruiting: Pre-collected samples only.

Governance and Ethical Approval

Governance and oversight:

Study Sponsor: Wellcome Sanger Institute

All work conducted at the Wellcome Sanger Institute is reviewed and overseen by institutional Research Governance processes, ensuring compliance with ethical, legal, and regulatory requirements.

Ethical approval:

This study has been reviewed by the South Central – Berkshire NHS Research Ethics Committee. The study received REC approval on 8 February 2023.

IRAS 324567

REC reference: 23/SC/0061

Data and Sample Use

Data sharing:

Anonymised DNA sequence data are stored in the European Genome-Phenome Archive (EGA) and made available to bonafide researchers via managed access, subject to data access agreements. Anonymised samples and cultured cells may also be shared with other legitimate research organisations under appropriate legal agreements.

IPD sharing statement

Deidentified individual participant-level data (IPD) will not be shared as part of this study.

Completion date

Ongoing

Further Information

For enquiries about the scientific aims of this study or potential collaboration, please contact the Bryant group.

For enquiries relating to research governance, ethics, or regulatory oversight, please contact the Research Governance team at researchgovernance@sanger.ac.uk.