Muscle proteins under surveillance

The Head of the Department of Structural and Computational Biology, Kristina Djinovic-Carugo, coordinates the EU project MUZIK, which is funded under the seventh framework programme. Eight partner universities and laboratories combine cellular and structural biology approaches to investigate the proteins of the muscle cell at different levels of complexity – from atomic structure to physiological function. The insights the scientists gain will help to understand the molecular processes in the muscle cell and could furthermore lead to novel treatment of muscular diseases. An important part within the project is to train young researchers as "Cellular Structural Biologists".

A muscle cell is a highly complicated and complex system. The structural biologist Kristina Djinovic-Carugo and her eight European partners are studying – within the EU project MUZIK (Muscle Z-disk Protein Complexes: From atomic structure to physiological function) – an even smaller part of the muscle cell, the so called Z-disk. "What makes the Z-disk so remarkable is that in this small part of the muscle cell the proteins are particularly densely packed. We are interested in these proteins and their specific structures and functions within the cell", Djinovic-Carugo explains.

The complexity of muscle cells

Muscles – both skeletal and heart muscles – are made of bundles of fibres and one of these fibres is a muscle cell. But it goes further down the scale: one muscle cell is itself made of identical building blocks, called sarcomeres, lined one beside the other. The "meeting point" of these sarcomeres is called the Z-disk, which again is a highly complex system in the cell because of the many different proteins and their versatile functions within it. "Even today scientists find new proteins in the Z-disk and also, as of today, not all the functions of the known proteins have been identified ", project leader Kristina Djinovic-Carugo says.

X-ray diffraction

Within the MUZIK network the scientists are looking into the structures of the Z-disk in order to understand the molecular processes going on. The main method they are using is crystallography: "We shine X-rays on the crystals of the molecule we want to determine the structure of and then we analyse the X-rays that are diffracted on the crystal", the project leader explains: "From the analysis of the X-rays diffracted on the crystal we can finally determine the structure of the molecule, meaning we are able to locate the position of the atoms of which the molecule is composed."

Of structure and functioning

At the same time the scientists of the MUZIK project are studying the functions of the different molecules in the Z-disk. Simply said, they not only want to know where the proteins are located within the Z-disk, their atomic composition and structure, but also what exactly they are doing there. "Therefore we also have several cell biologists in this network who are studying the function of the proteins on the one hand and, on the other, discovering proteins – this is not a finished story."

This kind of analysis – the combination of structure and function – can also explain the nature of various diseases. There are many muscle diseases which have to do with mutations of the proteins and by combining structural and functional studies can then understand the dysfunction. "Underlying every function is the structure of the proteins. Only if you really know the details of the structure of the proteins will you really understand its function", biologist Djinovic-Carugo explains.

The training of "Cellular Structural Biologists"

Closely connected to the research is the training of young scientists within the MUZIK project. This particular programme is called "Marie Curie Action: 'Networks for Initial Training'": Each of the eight partners within the network has at least one PhD student, some also have an additional postdoc to work with. "We want to generate a new, very versatile and marketable profile of scientists, namely cellular structural biologists", Kristina Djinovic-Carugo says: "Each student is closely involved in the research. Additionally, they all have a specific training package, including eight workshops and a complementary skills training, for example time management, project management or communication skills."

Many scientists know that it is not that easy to get funding from the European Union. This was actually the third attempt by Kristina Djinovic-Carugo to get this funding within the seventh frame programme. "It is very competitive, only about ten percent of applications are successful. We were really happy to finally get it. Beside the research and the training programme it is important for me to bring the community working in that field together, discuss problems and get new ideas." (td)

The EU project MUZIK (Muscle Z-disk Protein Complexes: From atomic structure to physiological function) funded under the seventh framework programme and also including Marie Curie Action: "Networks for Initial Training" started in November 2009 and will be finished in October 2013. Project leader and coordinator is Univ.-Prof. Dipl.-Ing. Dr. Kristina Djinovic-Carugo, Head of the Department of Structural and Computational Biology at the Centre for Molecular Biology and Max F. Perutz Laboratories, University of Vienna. The project partners are: University of Bonn, University of Padova (Italy), European Molecular Biology Laboratory (Germany), University of Jyväskylä (Finland), University of Leeds, King's College London, Technical University of Munich, Evitraproteoma AB (Sweden).