Understanding the role of ionocytes in a cystic fibrosis (CF) context using human induced pluripotent stem cell (hiPSC)-derived airway epithelial cells (AECs). (360G-Wellcome-218663_Z_19_Z)

Cystic Fibrosis (CF) affects over 10000 people in the UK. It is a recessive monogenic disease caused by a double mutation in the gene encoding for CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) and it affects multiple tissues, especially the lung. There is still no cure for this disease and patients require life-long treatment and eventually lung transplantation. This projects aims to study a newly discovered cell type in the human airway epithelium. These cells have been called pulmonary ionocytes because of their ion-exchange function and their similarity to ionocytes in Xenopus and zebrafish. Because they express high levels of CFTR, they have been proposed to have a key role in CF. I will derive airway epithelial cells, including ionocytes, from iPSCs from healthy and CF patients. I will do an extensive characterisation of the cells and I will study their role in the healthy and diseased epithelium using approaches such as single cell RNA-seq and assessment of cilia dynamics and mucus clearance. Overall, this project will shed light into the role of pulmonary ionocytes in the epithelium and into the pathophysiology of CF. This will lead to the identification of potential therapeutic targets and future treatments for the disease.