
COSS - Center for Optimized Structural Studies
- Head: Univ. Prof. Mag. Dr Kristina Djinovic-Carugo, Centre for Molecular Biology
- Grant recipient: Max F. Perutz Laboratories
- Partners: Intercell AG | Research Institute of Molecular Pathology | University of Vienna, Department of Structural and Computational Biology
Proteins in the third dimension
Being able to decode the structure of proteins means a better understanding of numerous processes in the body. Kristina Djinovic-Carugo, Head of the Department of Structural and Computational Biology at the University of Vienna’s Max F. Perutz Laboratories, investigates methods to chemically synthesise proteins and to examine their spatial dimension in the Laura Bassi Centre COSS.
Proteins are the building blocks of life and can be found in every cell: they transport endogenous substances and control the dynamics of cell reaction. They thus contribute significantly to the structure and the functioning of living organisms, controlling photosynthesis in plants, and metabolism as well as all biochemical reactions in humans. Knowing the spatial structure of a protein means a better understanding of numerous biological processes, which in turn makes disease research much more efficient. A human being is made up of 40,000 proteins, several thousands of which are known today. Once the structure of a protein is decoded it can be represented in colourful pictures, such as interwoven helices, folded spirals and globular chains. The majority of proteins have not been decoded yet because a single protein molecule consists of thousands of atoms and is so small that it cannot be detected even under the most exact microscopes.
Turning proteins into crystals
So other methods of visualisation must be applied. However, the so-called X-ray diffraction analysis requires proteins to be transformed into crystals first. Crystallisation research is the point of departure of the COSS research project because with many proteins it takes a great deal of effort to get them to crystallise. It involves numerous preliminary experiments to determine the optimal crystallisation conditions for every protein. Some proteins crystallise after a few experiments, others only after two to five years of intensive work. And then there are some proteins that never crystallise, despite decades of efforts in many laboratories. It is difficult to produce the large quantities of pure protein required by research for these experiments. This is why COSS researches innovative methods to produce sufficient quantities of high-quality protein that can be used for the crystallisation process.
Exposing proteins to radiation
To do so, COSS has chosen the following approaches: on the one hand, the team selects individual protein sequences to draw conclusions about their stability and the crystallisation requirements. On the other hand, Kristina Djinovic-Carugo attempts to increase the stability of the proteins through systematic reduction so as to enhance the probability of crystallisation. This is done to select the proteins that can be used best. When the crystallisation has been successful, the so-called X-ray diffraction analysis is carried out: the protein crystals are bombarded with X-rays. When a ray hits a crystalline atom grid, it is scattered according to the atomic structure, and the structure of the protein can be made visible atom by atom. The protein can then be displayed three-dimensionally on a screen, rotating it and zooming in. Today, teams of experts like COSS research the decoding of protein structures around the world.
Uncovering the structure of proteins
Kristina Djinovic-Carugo was born in Slovenia and studied Chemistry at the University of Ljubljana. While working on her master’s thesis she was the first to discover the structure of a certain molecule compound. This incident was pivotal in the further development of her career as a molecular biologist. Later, she did research in Pavia (Italy) and at the renowned European Molecular Biology Laboratory (EMBL) in Heidelberg, as well as in Trieste with the Research Group for Structural Biology and Crystallography at the ELETTRA Synchrotron Radiation Facility. In 2004, the University of Vienna appointed her professor of Macromolecular Crystallography at the Max F. Perutz Laboratories at the Campus Vienna Biocenter. The Max F. Perutz Laboratories, established in 2005, are a joint venture between the University of Vienna and the Medical University of Vienna. The collaboration between the two universities is a new and innovative approach to strengthen research and teaching at both universities. With regard to her Laura Bassi Centre, Kristina Djinovic-Carugo comments: “Excellence must always be the most important criterion in science. The Laura Bassi Centres promote excellent women on account of their excellent research achievements and not because they are women. As far as I’m concerned, that’s the way to do it.”
