SARCOSI · Sarcomere based Signals in Muscle Remodelling

The sarcomere is the structural unit of striated muscle tissues where thick and thin filaments cooperate to achieve muscle contraction. Recently it is becoming increasingly clear that sarcomeres have in addition to muscle contraction also important signaling functions: Stretch and strain sensing signalosomes are assembled by the giant muscle proteins titin and nebulin, that in turn are embedded into the sarcomere. Thereby, titin and nebuliun with dual structural scaffold and biosensing functions intricately connect the sarcomere to muscle remodelling.Molecular progress on titin- and nebulin based sarcomeric signalosomes has been accelerated during recent years, and the next step require is a functional understanding regarding how titin and nebulin and associated signaling complexes generate biochemical signals, and how these signals in turn, control muscle trophicity and remodelling. This network addresses this issue by bringing together teams leading in titin and nebulin muscle biology from America, Japan, and the US. Each team will contribute specific resources to study titin- and nebulin-based muscle remodelling, including transgenic animal models, compounds from high-throughput screens, and intricate myofibril mechanics. Importantly, SARCOSI will provide the European researchers resources that are otherwise not available.While the participants have collaborated and published together occassionally in the past, the SARCOSI network will establish long-term strategic EU transcontinental partnerships by staff exhanges and joint mentoring of thesis and postdoctoral projects. The exchange of staff will enhance the transfer of technologies and models between participating laboratories. By working close together and sharing resources, progress will be achieved much faster than working separately in the clinically important field of pathological muscle remodelling that contributes to both chronic heart failure and to skeletal muscle sarcopenia