Modelling Dystrophic Cardiomyopathy with iPSCs
If you have any partnering opportunities for Regener8 members, please contact us.
NESCI would be interested in funding / studentship opportunities for the following proposal.
NESCI are interested in industrial partners who may like to collaborate in one of these fields (for a CASE studentship or other awards), or in anyone who is interested in these areas of research (including other academic groups). For further details, please contact Helen Clamp from NESCI.
Project: Modelling Dystrophic Cardiomyopathy with iPSCs
Lead: Professor Hanns Lochmüller
A substantial proportion of Duchenne Muscular Dystrophy (DMD) patients develop dilated cardiomyopathy which becomes a life-limiting condition. However, very little is known regarding the phenotype of dystrophic cardiomyocytes, despite much work being done on skeletal muscle. Recent work has shown that cells with a pluripotent, embryonic stem (ES) cell phenotype can be derived from fibroblasts (induced pluripotent cells or iPSCs). This provides a unique opportunity to develop a model system for dystrophic cardiomyocytes, since ES cells can readily be differentiated into cardiomyocytes.
The student will derive fibroblast cultures from DMD patient skin biopsies, as well as control fibroblasts, and use them to derive iPSC lines which will be differentiated into cardiomyocytes. These will be used to examine the impact of dystrophin deficiency on cell viability, calcium handling properties, susceptibility to mechanical and osmotic stress and differentiation potential. Where dystrophic cardiomyocytes display aberrant properties, for example showing an increased propensity towards a fibrotic fate under stressful conditions, these properties will form the basis of novel intervention strategies designed to ameliorate the cardiac phenotype in DMD.
