Exploring the role of the LRRK2 kinase during infection
Research type
Research Study
Full title
Exploring the role of the Leucine-rich repeat kinase 2 (LRRK2) and its role in infection
IRAS ID
259992
Contact name
Esther Sammler
Contact email
Sponsor organisation
University of Dundee
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
Hyperactivating genetic changes in the Leucine rich repeat kinase (LRRK2) cause Parkinson’s disease. The physiological role of LRRK2 is poorly understood, but there is emerging data that that LRRK2 signaling is involved in immune defence mechanisms. The LRRK2 protein is highly expressed in immune cells, in particular neutrophils, which are the most abundant immune cell type within human peripheral blood. Neutrophils are also the major inflammatory cell population that infiltrate and accumulate within the airways of cystic fibrosis (CF) and bronchiectasis (BE) patients. These conditions promote airway colonization by several pathogens, such Pseudomonas aeruginosa leading to repeated respiratory tract infections that often require antibiotic treatment. We have robust assays to isolate neutrophils from peripheral blood as well as from sputum for measuring LRRK2 kinase pathway activity. We have pilot data demonstrating that the LRRK2 kinase can be activated by an ex vivo infection of human peripheral blood neutrophils with pathogens such as Pseudomonas aeruginosa. The current study aims to explore LRRK2 kinase pathway activity in vivo in patients with CF and BE throughout the course of an infect exacerbation and subsequent clearance with antibiotic treatment in sputum and peripheral blood neutrophils. The results of this study are expected to provide insight into the role of the LRRK2 kinase during infection in 2 different pools of neutrophils, blood vs sputum.
REC name
Wales REC 7
REC reference
19/WA/0035
Date of REC Opinion
6 Feb 2019
REC opinion
Favourable Opinion