• Darren Wilson - PhD Student

     

    Project: Investigating cardiomyocyte rigidity sensing and ion channel function in iPSC-CMs and dysfunction in dilated cardiomyopathy associated with muscular dystrophies

    Changes to cardiomyocyte mechanosensing are especially important in cardiomyopathies and specific examples of this is the dilated cardiomyopathy (DCM) occurring in muscular dystrophies, caused by mutations in the dystrophin (DMD) or fukutin-related protein (FKRP) gene. Dystrophin and its associated glycoprotein complex (DGC) connect the intracellular actin cytoskeleton to ECM ligands through highly glycosylated cell-surface receptor dystroglycan. FKRP is required for functional glycosylation of dystroglycan. In addition to progressive skeletal muscle wasting, muscular dystrophy patients also frequently suffer from DCM, characterised by an enlarged heart, poor contractile function and fibrosis. Development of DCM is a significant cause of death. Based on our preliminary data, we hypothesise that cardiomyocytes mechanosensing is dysfunctional in iPSC-CMs with DMD or FKRP mutations, as these will break the linkage between ECM and cytoskeleton.

    My project aims at developing in vitro human-specific cardiac models that will be then used to investigate the role of the DGC for mechanical sensing in cardiomyocytes using nanopillars, nanoindentation and electrophysiology studies.

     

    (Co-supervised by Andy Tinker & Yung-Yao Lin)