MUZIC · Muscle Z-disk Protein Complexes: from atomic structure to physiological function

Muscle Z-disk Protein Complexes: from atomic structure to physiological function

The heart is an essential organ in higher vertebrates and humans and its requirements for continuous operation are directly coupled with the total life span of these organisms. Temporary failure or even termination of its operation leads inevitably to death. Because of the strict requirement for durable and continuous operation it is not surprising that cardiac diseases are one of the top global killers, seriously threatening the present and future health status of the global community. The problem is further compounded by such negative factors as pollution, malnutrition, obesity, stress, drug consumption, and so on. To deal with this escalating problem there need to be new avenues of treatment, which in turn demands training of new generations of researchers through state-of-the-art research projects. MUZIC (http://www.fp7-muzic.eu) addressed this by creating an interdisciplinary training and research program, which focused on functional and structural studies of a specific muscle sarcomere compartment, the Z-disk. The Z-disk provides the attachment region for neighbouring sarcomere units and therefore plays a pivotal role in maintaining muscle architecture. Since sarcomeres from the heart and from skeletal muscles share many biologically similar functions, we have selected both cell types for functional and structural investigations. The main objectives of the MUZIC network are: • To bridge the gap between cellular and structural biology by creating a training program that will incorporate both disciplines in the study of molecular components and the cellular mechanisms of the muscle Z-disk. • To advance knowledge in the area of muscle Z-disk protein complexes, interactions and functions in healthy and diseased cells at molecular and cellular level. A large body of information has already been generated on the structure and function of the muscle Z-disk as a result of highly specialised and sometimes fragmented research, which has concentrated on either the molecular or cellular aspects. MUZIC is adopting a novel approach that integrates this knowledge into a larger context. The aim is to generate a comprehensive spatio-temporal picture of the muscle Z-disk interactome through use of an integrated, multidisciplinary analysis of its molecular components and the cellular mechanisms that are involved in its function, dynamics, and regulation, addressing the different levels of complexity, organisation, and cellular contexts, from the atomic structure to its physiological function. By synergising complementary state-of-the-art know-how from different MUZIC partners addressed the project aims by: • Sharing a pool of targets for different MUZIC projects goals. • The MUZIC project synergistically combines a set of leading structural and cellular biology methods. • Muscle Z-disk research– the research focus of MUZIC - is a bright example of a trans-disciplinary field that demands a new, versatile research profile at the interface of two disciplines – cellular and structural biology. MUZIC has provided a unique mix of cellular and structural biology laboratories with a focus on muscle research and combines a series of complementary state-of-the art know-how and technologies. The overall training aim is to enable a limited number of researchers to receive a career profile of a “Cellular Structural Biologist”. In order to train Cellular Structural Biologists and to achieve our scientific goals we designed the program to address the questions at different levels of complexity, organisation and cellular context: from atomic structure to physiological function, as depicted in Figure below. Figure 1. Programme design In the course of the project we filled 12/13 positions (8 ESRs and 4 ERs) through competitive selections by individual partners proceeded by joint advertisements. All ESRs but two, one of which had been on maternity leave, have received their doctoral degrees and most of them published their results in internationally peer-reviewed journals. The training programme has started timely, and all planned scientific workshops (Cloning, Expression and Purification of Eukaryotic Proteins and Protein and Biophysical characterisation and crystallisation, X-ray structure determination, Proteopedia of muscle Z-disk proteins, Electron microscopy, Effects of gene-silencing by genomic technologies, Protein-protein interactions, Atomic Force Microscopy and Molecular Mechanics) together with the summer school in Basic Fluorescence Microscopy) were offered to the trainees, flanked by the network meetings that took place approximately every 6 months and were composed of presentations of ESRs and ERs, principal investigators from Partner laboratories and invited speakers. All complementary skills workshops (Time and project management, Oral communication skills, Communication with public, Scientific English skills) have been performed as well. The project concluded with an international Conference "Myofibrillar Z-disk Structure and Dynamics" (www.fp7-muzic.eu/index.php?id=141&tx_ttnews[tt_news]=68&tx_ttnews[backPid]=1&cHash=a090217220). The conference was organised by the MUZIC scientist, who managed to invite a number of renowned international speakers, which in turn attracted an international pool participants.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз