Chronic obstructive pulmonary disease (COPD) is a prevalent inflammatory disease characterized by irreversible airflow obstruction as well as skeletal muscle wasting. The disease has high morbidity and mortality, and with more than 300 million deaths yearly, it is the 3rd leading cause of death worldwide. Disturbed damage and repair responses have been implicated in both lung and muscle pathology in COPD, resulting in airway disease, alveolar tissue destruction (emphysema) and skeletal muscle weakness. The tissue damage in COPD is severe and irreversible. Therefore, there is an urgent need to understand and target the mechanisms leading to impaired tissue regeneration in COPD. Emerging evidence implicates a role for mitochondrial impairment in lung and muscle pathology in COPD. Funded by a ZonMW-Open consortium grant, we will address this in our project.
Our project MITOREG aims to reveal the intricate interplay between MITOchondrial function and tissue REGeneration. We will investigate a novel concept on the crosstalk between lung and muscle. We will examine whether COPD-related mitochondrial dysfunction can be restored by stimulation of local and systemic mitochondrial rejuvenation in order to reinforce the regenerative capacity of muscle and lung.
Within the UMCG, the PhD student who will work on the lung epithelial cell culture studies, comparing mitochondrial function in primary epithelial cells from well-characterized COPD and control subjects and relating this to abnormal repair and regenerative responses, using advanced, patient-specific models including organoids and organ-on-chip. In addition, the PhD student will collaborate with the PhD student from Maastricht on lung-muscle interaction and potential interventions, using the organ-on-chip model set-up by a post-doc working in Verpoorte’s group.
Techniques to be used will be e.g. cell culture, using air-liquid interface and organoid models, electrical resistance measurements, mitochondrial respiration (Oroboros/Seahorse analyzer), qPCR, flow cytometry, ELISA, immunofluorescent staining, potentially mass spectrometry.