Molecular biotechnology: from dynamics of biological systems to applications
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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.
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