Molecular Physiology & Biophysics

Titin, the largest known protein, is indispensable for the structural integrity and function of the cardiac sarcomere. Yet, how such a massive ~3 mDa structural protein is maintained within the highly ordered sarcomere complex, while under continuously alternating tension, is unknown. My thesis focuses on elucidating the mechanisms mediating sarcomere homeostasis in human induced pluripotent stem cell-derived cardiomyocytes. Using CRISPR/Cas9 gene editing, I generated a novel model in which I can directly visualize sarcomeric titin in order to address fundamental questions regarding titin turnover, which is critical for sarcomere homeostasis.