Research profile
Research at the Institute of Molecular and Cellular Physiology focuses on molecular aspects of contraction and motility.
The research spectrum ranges from physiological and pathophysiological functional principles of heart muscle cells and skeletal muscle fibers to the investigation of isolated motor proteins at the single molecule level. A special focus is on the investigation of pathomechanisms of hypertrophic cardiomyopathy (HCM)
Main research topics
Research on pathomechanisms of Hypertrophic Cardiomyopathy (HCM) at several levels including analysis of basic functional mechanisms of the cardiomyocytes and the myocardium.
The focus here is on in-depth investigations of our "contractile imbalance" hypothesis. We assume that that the observed, spatially (and temporally) highly variable expression of mutated and wild-type protein in the individual cardiomyocytes of heterozygous HCM patients leads to a functional imbalance between the cardiomyocytes in the syncytium of the heart muscle. This could contribute significantly to the development of characteristic features of HCM such as disarray (cellular and myofibrillar disorder), hypertrophy and fibrosis. The aim is to contribute to the development of new therapeutic approaches.
Current questions:
- Is the stochastic, independent, burst-like transcription of wild-type and mutant alleles that we have observed for HCM mutations in β-cardiac myosin, cardiac troponin I (cTnI) and cardiac myosin-binding protein C (cMyBP-C) and the resulting functional variability of neighboring cardiomyocytes a major trigger for the development of HCM? Does this also apply to mutations in further sarcomeric proteins? find out more ...
- What role does the different expression of cardiac/non-cardiac isoforms of sarcomeric proteins in hPSC-CMs versus cardiomyocytes in the adult heart play for the function of myofibrils, isolated cells and cells in tissue? What can we derive from this for the understanding of cardiac contraction mechanisms and for changes observed in cardiac diseases? find out more ....
Characterization of molecular mechanisms of muscle contraction and function of motor proteins that are involved in intracellular transport and cellular motility, especially in the context of physiology and pathophysiology of the heart all the way to the single molecule level.
Current questions:
- What are the primary effects of HCM-associated mutations in sarcomeric proteins, of isoforms of contractile proteins, and of post-translational modifications such as phosphorylation and sumoylation on acto-myosin interaction and sarcomere function? This is being studied on isolated sarcomeric proteins in reconstituted systems and in cell culture models? find out more ....
- What can be deduced from this for cardiac contraction in HCM, or the loss of skeletal muscle function in cachexia? find out more ....
- Further points are the elucidation of mechanisms at the single molecule level of disease-associated changes in intracellular transport processes and movements of cells, 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 protein. In the long term, based on the single-molecule studies, development of bio-hybrid constructs with possible applications in nanotechnology is planned. find out more ....
Characterization and further maturation of human, stem cell-derived cardiomyocytes (hPSC-CMs) in direct comparison with human, adult cardiomyocytes, aiming at cell-based disease models for cardiomyopathies and development of new pharmacological intervention options in HCM.
Current questions:
- Which cellular mechanisms underlie the maturation of sarcomeric proteins and function as well as excitation-contraction coupling of hPSC-CMs? How can these mechanisms be activated in order to optimize the physiological functionality of hPSC-derived cardiomyocytes as test systems and disease models as well as in regenerative medicine? How do hPSC-CMs develop in surrounding tissue in terms of maturation and integration and how can integration be optimized? find out more ....
- What role does the different expression of cardiac/non-cardiac isoforms of sarcomeric proteins in hPSC-CMs versus cardiomyocytes in the adult heart play for the function of myofibrils, isolated cells and cells in tissue? What can we derive from this for the understanding of cardiac contraction mechanisms and for changes observed in cardiac diseases? find out more ...