KFO 192: Regulation und Fehlregulation von Muskelwachstum
Biologie
Zusammenfassung der Projektergebnisse
Skeletal muscle is the largest organ of the body. Fragility due to muscle weakness is a major health problem in the elderly and subsequent costs for hospitalization, rehabilitation and support are enormous. Accelerated degeneration of skeletal muscle is the hallmark of a large group of inherited muscular dystrophies and also of acquired myopathies. Inability to walk, respiratory failure and concomitant cardiac failure are typical in the course of these diseases. There is no treatment. The major aim of KFO192 “Regulation and dysregulation of skeletal muscle growth” was to bring together clinician and basic scientists from different specialties into a coordinated program of “Muscle Sciences”. At that time, a similar focus of any coordinated DFG programs did not exist in Berlin or in Germany. The team of researchers consisted of neurologists, pediatric neurologists, endocrinologists, anesthesiologists, physiologists and molecular biologists. During the first funding period we attemted to understand the role of a number of muscle proteins such as titin (TP1), dysferlin (TP6) ahnak (TP8) on muscle growth and metabolism and also studied severe muscular atrophy in clinical settings (TP2, cardiac cachexia; TP3, intensive care unit-acquired muscle weakness and atrophy (CIM)). During the second funding period the scientific focus of KFO192 shifted towards two highly successful areas in whom the combined effort of the majority of KFO-groups clearly demonstrated the benefit of a coordinated research program. To elucidate the pathophysiology of muscle wasting during critical illness TP3 (Weber-Carstens, Assmann), TP6 (Spuler), TP7 (Schülke), TP9 (Boschmann) TP12 (Spranger, Mai) and TP13 (Fielitz) closely cooperated from understanding molecular mechanisms of early muscle loss in CIM to clinical trials to prevent CIM. Skeletal muscle harbors its own pool of stem cells, satellite cells. Without these cells muscle cannot grow or regenerate. In a collaboration between TP11 (Birchmeier) and TP6 (Spuler) we investigated mechanisms of satellite cell quiescence in murine and human satellite cells. The possibility to apply the findings on human satellite cells for a future use as an ATMP (Advanced Therapeutic Medicinal Product) is currently explored and has led to further combined projects with additional grant support. Structurally, the integration of the KFO192 within the “Experimental and Clinical Research Center”, a cooperation of the Charité Universitätsmedizin Berlin and the Max Delbrück Center for Molecular Medicine within the Helmholtz Society has been somewhat unusual for a clinical research group, but proved to be institutionally and scientifically a foresightful and wise decision. However, it was the establishment of the International Research Training Group IGK1631 “MyoGrad” that helped to focus the science of KFO192 and delivered international visibility at the same time.
