Project descriptionCystic fibrosis (CF) is a genetic disorder caused by mutations in a gene called CFTR. This gene produces a protein (also called CFTR) that is an ion channel in the epithelial cells that line all the tubes in the body other than blood vessels. While lots of organs are affected, it is the airway disease that causes poor quality of life and early death. The CFTR ion channel defect results in dehydration of the airway surface liquid (ASL) and the inability to clear mucus via the normal clearance mechanism called mucociliary clearance (MCC). This creates the perfect environment for inhaled bacteria to grow in, causing a cycle of infection and inflammation that destroys lung tissue. One approach to treating CF airway disease is by using gene therapy. We have developed a lentiviral gene vector system that can add the CFTR gene into airway cells, producing long-term correction. However, one challenge is that when the vector fluid is delivered to the airways it naturally distributes rapidly into the alveoli, rather the conducting airways where it is needed. To overcome this we have conjugated our gene vector to magnetic particles (MP) that can be directed onto the airways with a magnetic field, increasing vector residence time. In studies at the SPring-8 Synchrotron in Japan, and our laboratory at the WCH we have shown proof of concept of this approach with a NdFeB rare-earth magnet. However, electromagnet approaches may result in better targeting. The aim of this project is to design, build and test an electromagnet system that could generate magnetic fields for accurately targeting MP deposition in live airways.
Assumed knowledgeA strong understanding of the physics of magnetic fields would be valuable.
Supervisors research focusThe Cystic Fibrosis Airway Research Group (CFARG) and Respiratory X-ray Imaging Laboratory (ReXIL) are located in Respiratory Medicine in the Gilbert Building at the Women’s and Children’s Hospital. We are dedicated to developing gene-based therapies for CF lung disease, as well as novel imaging-based methods for assessing the effectiveness of therapies.
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