Research profile
Research at the Institute of Molecular and Cellular Physiology focuses on the physiological and pathophysiological mechanisms of striated muscle. Studies of the molecular aspects of contraction and motility range from the cellular and subcellular levels to the investigation of motor proteins at the single-molecule level. A particular focus is on researching the pathomechanisms of hypertrophic cardiomyopathy (HCM).
Main research topics
Research into the pathomechanisms of hypertrophic cardiomyopathy (HCM) at multiple levels, with a focus on the fundamental functional mechanisms of cardiomyocytes and the myocardium.
The focus here is on in-depth investigations of our “contractile imbalance” hypothesis. We hypothesize that the observed, highly variable spatial (and temporal) expression of mutated and wild-type protein within individual cardiomyocytes of heterozygous HCM patients leads to a functional imbalance among the cardiomyocytes in the cardiac muscle syncytium. This could contribute significantly to the development of characteristic features of HCM, such as disarray (cellular and myofibrillar disorganization), hypertrophy, and fibrosis. The goal is to contribute to the development of new therapeutic approaches. Read more....
Current Questions:
Is the stochastic, independent burst -like transcription of wild-type and mutated alleles—and the resulting functional imbalance (contractile imbalance) between neighboring cardiac muscle cells—a key basis for the pathogenesis of HCM? Does this also apply to mutations in other sarcomeric proteins? Read more ...
What cellular mechanisms underlie the maturation of hPSC-CMs with regard to the expression of sarcomeric proteins, sarcomere function, and electromechanical coupling? How can these mechanisms be activated to optimize the functionality of hPSC-CMs as test systems and disease models, as well as in regenerative medicine? How do hPSC-CMs continue to develop within tissue constructs in terms of maturation and integration, and how can integration be optimized? Read more ...
What role does the differing expression of cardiac and non-cardiac isoforms of sarcomeric proteins in hPSC-CMs and cardiomyocytes in the adult heart play in the function of myofibrils, isolated cells, and cells within tissue constructs? What can we infer from this regarding our understanding of cardiac contraction mechanisms and changes associated with cardiac diseases? Read more ....
Characterization and further maturation of cardiomyocytes derived from human pluripotent stem cells (hPSC-CMs) in direct comparison with human adult cardiomyocytes, with the aim of developing cell-based disease models for cardiomyopathies and new pharmacological intervention strategies for HCM.
Current Questions:
What cellular mechanisms underlie the maturation of hPSC-CMs with regard to the expression of sarcomeric proteins, sarcomere function, and electromechanical coupling? How can these mechanisms be activated to optimize the functionality of hPSC-CMs as test systems and disease models, as well as in regenerative medicine? How do hPSC-CMs continue to develop within tissue constructs in terms of maturation and integration, and how can integration be optimized? Read more....
What role does the differing expression of cardiac and non-cardiac isoforms of sarcomeric proteins in hPSC-CMs and cardiomyocytes in the adult heart play in the function of myofibrils, isolated cells, and cells within tissue assemblies? What can we infer from this regarding our understanding of cardiac contraction mechanisms and changes associated with cardiac diseases? Read more....
Characterization of molecular mechanisms of contraction and the function of motor proteins involved in intracellular transport and cellular motility, down to the single-molecule level, particularly in the context of cardiac physiology and pathophysiology.
Current Research Questions:
What effects do different isoforms and post-translational modifications of contractile proteins, as well as HCM-associated mutations in sarcomere proteins, have on actin-myosin interaction and sarcomere function? This is being investigated at the level of isolated sarcomere proteins in reconstituted systems and in cell culture models. Read more....
Another focus is the elucidation—down to the single-molecule level—of molecular mechanisms and their disease-associated alterations with regard to intracellular transport processes and cell movements, which are mediated by myosins and motor proteins of the kinesin and dynein families and regulated by microtubule-associated proteins such as Alzheimer’s-associated tau. In the long term, bio-hybrid constructs with potential applications in nanotechnology will also be developed based on these single-molecule studies. Read more....
Regulation of Skeletal Muscle Organization and Muscular Dystrophy by Small Ubiquitin-like Modifiers (SUMO).
