Molecular Biotechnology: from Dynamics of Biological Systems to Applications

Life sciences experience the transition from molecular to the systemic level, fostering the development of a new quality in our understanding of complex biological systems such as immune and metabolic system. Program connects basic research with application in the areas of research, which have primarily relevance to the health. The emphasis of the program is on the understanding of the response of the human organism to bacterial infections and conformational diseases at the molecular level and understanding of the microbial metabolism directed towards the improvement of the various pharmaceutically interesting products. Within the research of the LPS receptors we will investigate the extracellular (MD-2, TLR4, CD14) as well as intracellular receptors. Understanding of interactions at the molecular level can lead to new compounds, which might be used to neutralize the excessive immune response. The aim of this research is to elucidate the biochemical specificity of the so called “PAMP receptors”, i.e. receptors that recognize the molecular patterns of pathogenic microorganisms. Based on the structure-activity relationship (SAR) we plan to develop new (lipo)peptides and establish the differences in the selectivity between bacterial and eukaryotic membranes. In the area of health we are also investigating diseases, particularly transmissible spongiform encephalopathies (TSE) connected to conformational changes of proteins. Monoclonal antibodies have been established as diagnostic tool as well as for the therapy. By the combination of immunochemistry with methods of protein and structural biochemistry we made the first step analyzing the specificity of antibodies that recognize the pathogenic form of prion protein (PrPSc), linked to Creutzfeld-Jakob disease. This and other tools will allow us to improve the detection and early diagnostics of disease and in parallel to contribute to the understanding of the infectivity of TSE. Program also involves the research of primary metabolism of industrial microorganisms, particularly 6-phosphofructo-kinase (pfkA), whose properties significantly change during the posttranslational modification. We intend to transfer the shortened gene encoding more active enzyme into other commercially important microorganisms. We will develop the new fluorescent intracellular biosensors to monitor the events particularly in eukaryotic cells. We will put the emphasis on the analysis of Ca, cAMP and pH inside of living cells.

Achievements of the program Molecular Biotechnology represent an important contribution of science in understanding the molecular mechanism of innate immunity signaling, which advanced significantly in the last decade. In addition to understanding the basic mechanisms of recognition and signaling the results are relevant for a wide range of pathological phenomena from infections, chronic inflammation to cancer and for understanding and improving the treatment of these diseases. Members of the program group significantly shaped the development of synthetic biology in the world in recent times. The group introduced a concept of designable modularity, which means the use of protein domains that can be prepared in a number of variants, with the help of which one can make a new modular structures or introduce the cell logic. Such modular building components are coiled-coil dimers for the preparation of new types of protein folding process which defines the topology, which is probably the most original contribution of this group to science in the last period. Preparation of protein tetrahedron experienced a remarkable recognition in the scientific community. The second group of modular building blocks are DNA binding proteins based on TALE domains, which enabled preparation of orthogonal NOR gates and bistable gene switch. Additionally, we can highlight the design of biosynthesis frame on the substance of DNA and DNA binding domain which improved the production of three reactions and has been followed by other scientists.

Research program Molecular Biotechnology is important for Slovenia because it is among the leading groups in research of innate immunity and synthetic biology. The program allows contact with the cutting edge science on these two areas, which are important for health as well as the increasingly important for the technology. The program group has the important role in training qualified researchers who are able to solve complex scientific and developmental problems. The success of the group in the field of science and higher education and intensive international involvement are important for the promotion of Slovenia as a developed country and an important partner. Cooperation with companies in the field of high technology allows the transfer of scientific advances in industrial applications with partners in Slovenia and around the world. The group is also important for the promotion of science as a key factor in the successful development and part of the intellectual identity in Slovenia at the level of secondary school students, their mentors, students, researchers, politicians and the general public.