Drug Modulated Dynamics of Macrophage Surface Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Protein

Abstract

Cystic fibrosis (CF) is one of the common genetic autosomal diseases that is caused by a genetic mutation of the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel. The available treatments that target CFTR protein have shown effectiveness in the reduction of symptoms in patients, thus, increasing their life expectancy. Despite drugs being vital for CF, the availability of clinically approved ones that target CFTR is limited and this is partially due to drug testing limitations and clinical trials (being expensive and time-consuming). Hence there is a dire need for effective drug testing strategies that allow for both high throughput and high content studies. This research proposed the development of a toolkit using microfabrication approaches and bioelectronics (Lab-on-chip) to enhance current in vitro assays by combining state-of-the-art (endpoint) techniques (i.e., immunofluorescence) with new assays (i.e., electrochemistry) to test CFTR dynamics. The developed Cystic Fibrosis LoC demonstrated a remarkable sensitivity in detecting cell adhesion to the surface of the electrode and detecting the effects of channel blocking. Our work and the tools we have developed will lay the foundation for enhancing cell-based assays for ion channel testing such as the case of CFTR and cystic fibrosis.

Date of Award	21 Dec 2023
Original language	American English
Supervisor	Herbert Jelinek (Supervisor)