Chronic obstructive pulmonary disease (COPD) is a lung disease affecting 10% of adults in the UK. It causes symptoms of breathlessness, cough and sputum production. COPD endotypes include eosinophil-mediated inflammation, which indicates an increased risk of cardiovascular disease (CVD). Eosinophils are a type-2 mediated inflammatory cell with a range of effects including allergic and host immune responses. The mechanism by which eosinophils confer an increased cardiovascular risk in COPD is unknown. This project will seek to understand this.
1. Investigate the interaction effects of platelets and eosinophils from patients with COPD
2. Determine the signalling pathways that are dependent on platelet-eosinophil aggregation
3. Understand how corticosteroid treatment in COPD may have therapeutic protection from cardiovascular disease
This work is translational. Patients with COPD, with or without cardiovascular disease will be sampled for experiments and conditions compared to controls. You will be competent in sample preparation, cell isolation, co-culture, flow cytometry, microscopy, molecular techniques, ELISA, statistical analysis, and the understanding of COPD in humans. You will present your data to the group, nationally and internationally and critique the work of others in the same field.
Year 1. Establish essential methodologies such as sample preparation (sputum and whole blood), cell isolation, cell counting, co-culture experiments and ELISA. Obtain Good Clinical Practice competencies, work in a team, attend COPD clinics as an observer
Year 2. Develop flow cytometry techniques and derive antibody-flow panels that can investigate the function and interaction of eosinophils and platelets in conditions of i) health; ii) COPD-CVD+ and iii) COPD-CVD-. Determine sample size to power your experimental plan
Year 3. Determine the effect on common COPD treatment (corticosteroids) on eosinophil-platelet interactions in groups i-iii described above
Year 4. Investigate molecular pathways that confer increased risk of CVD in patients with COPD.