SARCOSI

Sarcomere based Signals in Muscle Remodelling

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 Obiettivo del progetto (Objective)

'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'

Introduzione (Teaser)

A multidisciplinary consortium is investigating muscle signalling in health and disease. The generated information should improve our understanding of various primary and secondary myopathies.

Descrizione progetto (Article)

Skeletal and cardiac muscles have a distinct structure known as the sarcomere, which is responsible for a muscle's ability to contract. Accumulating evidence indicates that the sarcomere also has signalling functions partly mediated by two of its key proteins, titin and nebulin.

In addition, it is becoming increasingly apparent that impaired muscle contractility is a frequently observed phenomenon in various diseases. This impairment could be secondary, such as in the case of metabolic disorders or chronic heart failure, or could be the direct cause of physical inactivity. Taken together, these observations portray a complex interconnection between muscle activity state, metabolism, life style and chronic disease, calling for further investigation.

With this in mind, scientists on the EU-funded 'Sarcomere based signals in muscle remodelling' (http://sarcosi.org/ (SARCOSI)) project have set out to understand how impaired muscle contractility develops in disease states and how this further contributes to pathology. The consortium consists of multidisciplinary research teams and clinical experts in the field from Brazil, Japan and the United States, aiming this way to overcome research fragmentation.

Special focus is given to the role of nebulin, which is critical for the sarcomere structure and myofibril force production. By studying patients with nemaline myopathy, who lack the protein nebulin, the consortium hopes to deliver a potential therapeutic approach. To study the underlying mechanism and screen the therapeutic efficacy of various drugs, researchers have developed novel mouse models for the disease.

Another important project feature is its coordination of muscle research and fundraising. It has so far worked as a platform for intercontinental collaborations and for obtaining long-term research funding.

Collectively, work by the SARCOSI initiative is expected to have an extensive translational impact and provide answers for various conditions associated with pathological muscle remodelling.