Topics proposed for cooperation

CIPKEBIP Principal investigators prepared some topics for cooperation at different kind of calls (national and international ones) for project proposals. If your organisation is willing to cooperate with CIPKEBIP researchers, please contact the management of the centre of excellence or directly the researcher who proposed the topic.

Prof.Dr. Dušan Turk

Affiliation: Department of Biochemistry and Molecular Biology B1 at Jožef Stefan Institute, Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, Scientific Director and Principal Investigator Dusan Turk

Keywords: vaccine discovery, immune system response, antigenic targets, endosomal degradation

Research interest: The group has a long term interest in unraveling molecular mechanisms of antigen presentation at “in vitro” level. We think that understanding of endosomal degradation of protein samples is one of the key issues in vaccine discovery. For this purpose we study and characterize endosomal enzymes (proteases, hydrolases, reductases), their protein inhibitors, MHC class II molecules, and antigenic proteins and their interactions. Characterization of players and their interactions is biochemical (kinetics, protein stability) and structural (crystal structure determination).

We think that the generated antigenic peptides are a result of competitive assays performed within the antigen presented cells, where a number of endosomal compartments with a variable enzyme and inhibitor composition tries to generated antigenic peptides by degradation of foreign molecules. Only successfully processed peptides are loaded to MHC class II molecules and presented at the cell surface.

Research goal: Produce a system for in vitro generation of antigenic peptides. The experiments will take into account also the time component. We are setting up a robotic system to perform automated sample mixing and analysis of hydrolized products. The assay ingredients are enzymes and antigenic proteins. Enzymes are mixed in a combinatorial setup. The expected outcomes of this analysis are identification of potential antigenic determinants (peptides, carbohydrates) and ranking of antigenic proteins for their suitability for antigenic peptides generation. Ranking may assist in screening of proteins to be used for vaccination.

Technological expertise: Protein expression is based on a medium throughput approach using tools for parallel and continuous expression efforts developed by the “structural genomics” consortia. Four systems are used: E. Coli, pychia (in lesser extent), insect and mammalian cells. The system has the capacity to deal with protein expression and purification approximately 100 targets simultaneously, each at different level of expression.
We have a working platform for crystal structure determination from crystallization onwards.

Two recent publications:

Mihelic, M, Doberšek, A, Guncar, G., Turk, D. (2008) Inhibitory fragment from the p41 form of invariant chain can regulate activity of cysteine cathepsins in antigen presentation
J Biol Chem. 2008 May 23;283(21):14453-60.

Renko M, Sabotic J, Mihelic M, Brzin J, Kos J, Turk D. (2010) Versatile loops in mycocypins inhibit three protease families. J Biol Chem. 285(1):308-16.

Back to the top

Prof. Dr. Igor Križaj

Affiliation: Department of Molecular and Biomedical Sciences at Jozef Stefan Institute (, Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, Principal Investigator: Igor Križaj

Keywords: secreted phospholipases A2, neuromuscular communication, lipid signalling, lipid-associated disorders, cancer, haemostasis, protein structure

Research interests: The main research topic of the group are secretory phospholipases A2 (sPLA2s), originating from either animal venoms or mammalian tissues. Secretory PLA2s are esterases that hydrolyze the sn-2 ester bond of glycerophospholipids. Products of their enzymatic activity, fatty acids and lysophospholipids, and also sPLA2s acting as ligands for tissue receptors are involved in numerous physiological and pathological processes in organisms. We are particularly interested in explaining the molecular mechanisms underlying (patho)physiological effects of neurotoxic and anticoagulant snake venom sPLA2s. The mammalian genome encodes for ten enzymatically active sPLA2s and two sPLA 2-related proteins devoid of lipolytic activity, homologous and highly similar to snake venom sPLA2s. The mammalian genome encodes also several types of sPLA2-binding proteins. These proteins are crucially involved in many aspects of cell signalling, immunity and an array of pathologies including atherosclerosis, cancer, obesity, diabetes, inflammation and neurodegenerative disorders. We are mainly focused on the role of sPLA2s in breast, prostate and colorectal cancers, peroxisome and mitochondrial function. We are also interested in the mechanisms of cell response to perturbation of biological membranes.

Research goal: By deepening our understanding of how snake venom sPLA2s endowed with presynaptic neurotoxicity influence the nerve function and haemostasis we are looking forward to develop innovative molecular tools to study nerve function (e.g. exo- and endocytosis) and dysfunction (neurodegeneration and regeneration), haemostasis (diagnosis and treatment of blood coagulation disorders), and to develop more efficient envenomation protection and therapy procedures. We are trying to explain the role of endogenous sPLA2s in cell proliferation and apoptosis, specially focusing on their function in breast cancer.

Technological expertise: Besides standard protein biochemistry and enzymology, standard molecular biology, protein engineering, immunology and cell biology, the group has more than twenty years of tradition in the protein primary structure analysis. We are equipped and trained to study interfacial enzymology on membrane surfaces, to perform membrane and protein-protein binding studies (SPR), to radiolabel proteins, to study protein secondary structure, to perform fluorescence microscopy, transcriptomics, yeast molecular biology and high-throughput genetics studies (SGA, SDL and chemical genomics), proteomics, standard evolutionary genomics and bioinformatics.

A few selected recent publications:

Mattiazzi, M., Jambhekar, A., Kaferle, P., DeRisi, J.L., Križaj, I. and Petrovič, U. (2010): Genetic interactions between a phospholipase A 2 and the Rim101 pathway components in S. cerevisiae reveal a role for this pathway in response to changes in membrane composition and shape. Mol. Genet. Genomics 283, 519–530.

Logonder, U., Jenko-Pražnikar, Z., Scott-Davey, T., Pungerčar, J., Križaj, I. and Harris, J. (2009): Ultrastructural evidence for the uptake of a neurotoxic snake venom phospholipase A2 into mammalian motor nerve terminals. Exp. Neurol. 219, 591–594.

Kovačič, L., Novinec, M., Petan, T., Baici, A. and Križaj, I. (2009): Calmodulin is a non-essential activator of secretory phospholipase A2. Biochemistry 48, 11319–11328.

Jenko Pražnikar, Z., Kovačič, L., Rowan, E.G., Romih, R., Rusmini, P., Poletti, A., Križaj, I. and Pungerčar, J. (2008): A presynaptically toxic secreted phospholipase A2 is internalized into motoneuron-like cells where it is rapidly translocated into the cytosol. Biochim. Biophys. Acta – Mol. Cell Res. 1783, 1129–1139.

Back to the top

Prof. Dr. Marjan Slak Rupnik

Affiliation: Institute of Physiology at the Faculty of Medicine (http://, Centre of excellence for integrated approaches in chemistry and biology of proteins, Principal Investigator: Marjan Rupnik

Keywords: beta-cell physiology, tissue slice, patch-clamp, multi-photon imaging, diabetes mellitus

Research interest: The group has a long term interest in unraveling physiology of endocrine pancreas which is important in regulation of human body metabolism. Particularly we would like to discover molecular mechanisms controlling the late stages of intracellular vesicular trafficking underlying exocytotic process in calcium-dependent insulin release from beta-cells.

Research goal: The primary research goal of our laboratory is to assess the role of protein kinases, like PKA, PKC, Cdk5 on the calcium-dependent secretory activity in cells of endocrine pancreas. Our previous studies on the diabetic animal models showed that hyperactivity of PKC leads to glucose intolerance and diabetes mellitus; however this status could be rescued by activation of PKA. Due to epidemic dimensions of diabetes mellitus in the human population, detailed knowledge about the physiology and pathophysiology of the hormone secretion from pancreas should have a significant socio-economic impact.

Technological expertise: Our laboratory has a background in endocrine physiology and is a global reference laboratory for endocrine tissue slice approaches, particularly the whole pancreas slices. We use advanced approaches in electrophysiology and combine them with state-of-the-art confocal and multi-photon microscopy.

A few publications:

Skelin M, Rupnik M. cAMP increases the sensitivity of exocytosis to Ca(2+) primarily through protein kinase A in mouse pancreatic beta cells. Cell Calcium. 49(2):89-99.

Huang YC, Rupnik M, Gaisano HY Unperturbed islet -cell function examined in mouse pancreas tissue slices. J Physiol. 2011 Jan 15;589(Pt 2):395-408.

Paulmann N, Grohmann M, Voigt JP, Bert B, Vowinckel J, Bader M, Skelin M, Jevsek M, Fink H, Rupnik M, Walther DJ. Intracellular serotonin modulates insulin secretion from pancreatic beta-cells by protein serotonylation. PLoS Biol. 2009 Oct;7(10):e1000229.

Rose T, Efendic S, Rupnik M (2007) Ca2+-secretion coupling is impaired in diabetic Goto Kakizaki rats. J Gen Physiol. 129(6):493-508.

Speier S, Gjinovci A, Charollais A, Meda P, Rupnik M (2007) Cx36-Mediated Coupling Reduces beta-Cell Heterogeneity, Confines the Stimulating Glucose Concentration Range, and Affects Insulin Release Kinetics. Diabetes. 56(4):1078-86.

Meneghel-Rozzo, T., Rozzo, A., Poppi, L., Rupnik M. (2004) In vivo and in vitro development of mouse pancreatic β-cells in the organotypic slices. Cell Tiss Res, 316:295-303.

Speier, S, Rupnik M. (2003) A novel approach to in situ characterization of pancreatic b-cells. Pflugers Arch-Eur J Physiol 446(5) 553-558.

Back to the top

Prof. Dr. Sašo Džeroski

Affiliation: Department of Knowledge Technologies ( at Jožef Stefan Institute, Centre of excellence for integrated approaches in chemistry and biology of protein, Principal Investigator: Sašo Džeroski.

Keywords: machine learning, equation discovery, structure prediction, bioinformatics

Research interest: The group performs research in advanced information technologies, aimed at managing knowledge to be used in the development of knowledge-based applications. Established areas of knowledge technologies include intelligent data analysis (machine learning, data mining, knowledge discovery in databases), text and web mining, semantic web, social network analysis, language technologies, decision support and knowledge management. We apply these technologies to practical problems in the areas of environmental and life sciences, medicine and health care, economy and marketing.

Research goal: The availability of new, highly effective tools for biological exploration is dramatically changing the way one performs research. The amount of available experimental data is not a limiting factor any more and the challenge has shifted towards identifying the relevant pieces of information and making sense out of it (a "data mining" issue). Machine learning naturally appears as one of the main drivers of progress in this context, where most of the targets of interest deal with complex structured objects: sequences, 2D and 3D structures or interaction networks. At the same time biology has already induced significant new developments in machine learning, for example in the context of learning with structured data, graph inference, semi-supervised learning, system identification, and novel combinations of optimization and learning algorithms. We will develop machine learning approaches for structure prediction and integrative data analysis and use them on problems of protein structure and function prediction.

Technological expertise: The group has ample experience in development and use of machine learning and data mining approaches and techniques. These include approaches for modelling dynamics and structure prediction, such as equation discovery, relational data mining (inductive logic programming), and decision trees/rules for structure prediction. These techniques have been applied to practical problems in the area of environmental sciences (e.g., modelling the co-existence of conventional and genetically modified crops), environmental epidemiology and life sciences/systems biology (e.g., finding biomarkers for embryonal tumors, genome-wide gene/protein function prediction for bacterial pathogens).

A few publications:

S. Džeroski, L. Todorovski. Equation discovery for systems biology: finding the structure and dynamics of biological networks from time course data. Current Opinion in Biotechnology, 19: 360-368, 2008.

S. Džeroski, and L. Todorovski, editors. Computational Discovery of Scientific Knowledge. Springer, Berlin, 2007. Lecture Notes in Artificial Intelligence, Volume 4660.

L. Schietgat, C. Vens, J. Struyf, H. Blockeel, D. Kocev, S. Džeroski. Predicting gene function using hierarchical multi-label decision tree ensembles. BMC Bioinformatics, 11:2, 2010.

Back to the top

Prof. Dr. Maja Rupnik

Affiliation: Institute of Public Health Maribor (, Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, Principal Investigator: Maja Rupnik

Keywords: Cellular microbiology, molecular typing, bacterial pathogenesis, toxins, microbiota, virulence factors

Research interests: The main research topic of the group are virulence properties of pathogenic bacteria, in particular Clostridium difficile and Staphylococcus aureus, such as toxins and their interactions with host cell, adhezins, biofilm formation, hypermutable phenotype, antibiotic resistance, colonization resistance and composition of normal host microbiota in health and disease. By using molecular typing methods we follow the epidemiology of nosocomial pathogens.

Research goal: To understand differences between microorganisms causing mild or severe forms of disease and to use such differences as diagnostic markers or therapeutic targets. Clostridia and staphylococci associated with more severe forms of the disease could have variations in some antigens (surface adhesions, toxins) that cause differential processing and hence different development of immune response. Also, novel virulence properties such as new toxic or new immunomodulatory molecule could be expected. Strains with increased virulence could in addition better avoid colonization resistance provided by normal human microbiota (e.g. in the gut).

Technological expertise: The group has modern molecular biology equipment (real-time and conventional PCR, DGGE, pulse field electrophoresis), denaturing high performance liquid chromatography for analysis of complex DNA mixtures (DHPLC), MIDI system for semi automatic identification of bacteria, and cell culture lab.

A few selected recent publications:

Greco A, Ho JG, Lin SJ, Palcic MM, Rupnik M, Ng KK. (2006) Carbohydrate recognition by Clostridium difficile toxin A. Nat Struct Mol Biol., 13: 460-461.

Reineke J, Tenzer S, Rupnik M, Koschinski A, Hasselmayer O, Schrattenholz A, Schild H, Von Eichel-Streiber C. (2007) Autocatalytic cleavage of Clostridium difficile Toxin B. Nature, 446: 415-419.

Rupnik M . (2008) Heterogeneity of large clostridial toxins: importance of Clostridium difficile toxinotypes. FEMS Microbiol Rev., 32(3): 541-555.

Pokorn, M., Radšel, A., Čižman, M., Jereb, M., Karner, P., Kalan, G., Grosek, Š., Andlovic, A., Rupnik M. (2008) Severe Clostridium difficile associated disease in children. Pediatr Infect Dis J 27: 944-946.

Rupnik M , Wilcox MH, Gerding DN. (2009) Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nature Rev Microbiol. 7(7):526-36. Review.

Zemljič M., Rupnik M, Scarpa M, Anderluh G, Palu G, Castagliuolo I. (2010) Repetitive domain of Clostridium difficile toxin B exhibits cytotoxic effects on human intestinal epithelial cells and decreases epithelial barrier function. Anaerobe, 16: 527-532.

Janezic S., Rupnik M., (2010) Molecular typing methods for Costridium difficile: pulsed-field gel electrophoresis and PCR ribotyping. V: Mullany P, Roberts A (Eds.), Clostridium difficile, Methods and Protocols; Springer Protocols – Methods in Molecular Biology (Walker JM, Series Ed.), vol. 646, Humana Press, 2010, pg. 55-66.

Rupnik M. (2010) Clostridium difficile : (re)emergence of zoonotic potential. Clin. Infect. Dis., 51: 583-584.

Bauer M. P., Notermans, D. W., Benthem B. H.B. van, Brazier J. S., Wilcox M., Rupnik M., Monnet D. L., Dissel J. T. van, Kuijper E. J. (2011) Clostridium difficile infection in Europe : a hospital-based survey. Lancet 377(9759):63-73.

Back to the top

Prof. Dr. Nina Gunde-Cimerman

Affiliation: University of Ljubljana, Biotechnical Faculty, Department of Biology; Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, Principal Investigator: Nina Gunde Cimerman

Keywords: extremotolerance, stress tolerance, fungi, stress adaptation mechanisms, evolution of stress tolerance

Research interest: The aim of the research group is a significant advancement in knowledge in the field of adaptation to stressful conditions in eukaryotic cells. By using stress-tolerant fungi as new model organisms for studying extremotolerance, we are studying molecular mechanisms enabling survival in extremely stressful conditions. We are also interested in evolution of life under stress and the resulting biodiversity in natural as well as man-made extreme environments.

Research goal: We are trying to identify the genetic/genomic background of extremotolerance by using various approaches from classical genetics to genomics and transcriptomics. Our ultimate goal is to associate the resulting knowledge with the research on evolution and diversity in extremely stressful environments and apply it for solving important problems of the modern world: (a) climate changes result in frequent droughts and salinization of the agricultural land; subsequent loss of productivity could be overcome with engineering crops with increased drought and salt tolerance by transferring the appropriate genes; (b) emerging fungal pathogens represent a significant medical challenge; our recent data suggest that adaptation to stressful environments may be tightly linked with the evolution of virulent factors required for human pathogenesis; (c) extreme environments are significantly affected by global climate changes; according to our data this may lead to disruption of a rich diversity and very specific evolutionary processes in these environments.

Technological expertise: general molecular biology techniques; molecular and microbiological techniques for handling non-conventional fungi; fungal genomics, transcriptomics and lipidomics; analyses in fungal phylogeny, taxonomy and molecular evolution

Selected publications:

Butinar, L., Spencer-Martins, I., and Gunde-Cimerman, N. (2007) Yeasts in high Arctic glaciers: the discovery of a new habitat for eukaryotic microorganisms. Antonie Van Leeuwenhoek 91: 277-289.

Gostinčar, C., Grube, M., Hoog, S.d., Zalar, P., and Gunde-Cimerman, N. (2010) Extremotolerance in fungi: evolution on the edge. FEMS Microbiology Ecology 71: 2-11.

Gunde-Cimerman, N., Zalar, P., de Hoog, S., and Plemenitaš, A. (2000) Hypersaline waters in salterns - natural ecological niches for halophilic black yeasts. FEMS Microbiol Ecol 32: 235-240.

Kogej, T., Stein, M., Volkmann, M., Gorbushina, A.A., Galinski, E.A., and Gunde-Cimerman, N. (2007) Osmotic adaptation of the halophilic fungus Hortaea werneckii: role of osmolytes and melanization. Microbiol 153: 4261-4273.

Sonjak, S., Frisvad, J.C., and Gunde-Cimerman, N. (2006) Penicillium mycobiota in arctic subglacial ice. Microb Ecol 52: 207-216.

Turk, M., Abramovic, Z., Plemenitas, A., and Gunde-Cimerman, N. (2007) Salt stress and plasma-membrane fluidity in selected extremophilic yeasts and yeast-like fungi. FEMS Yeast Res 7: 550-557.

Back to the top

Prof. Dr. Nataša Poklar Ulrih

Affiliation: Chair of Biochemistry and Food Chemistry at Department of Food Science and Technology at Biotechnical Faculty, University of Ljubljana (, Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins (, Principal Investigator: Nataša Poklar Ulrih

Keywords: bioactive compounds, interactions of polyphenolic compounds with proteins, membranes and DNA, extremophilic archaea, thermally stable enzymes, archaeosomes, protein aggregations

Research interests: The main research topic of the research group are phenolic compounds and other secondary metabolites in plants. Physicochemical characterization of food additives (sweeteners, antioxidants). Influence of environmental factors on polyphenolic compounds and antioxidant activity. Comparison of model systems (interaction of flavonoids with model cell membrane) for the study of antioxidant activity of plant extracts. By-products of plant processing as a sources of bioactive compounds: oil meals (solid residues in oil production), hop leafs. Bioavailability of the phenolic compounds and their effect on health. Hyperthermophilic acrhaea as a source of thermally stable antioxidants, enzymes and archeosomes – systems for encapsulation of bioactive components.

Research goal: One of our primary research goals is to study the bioavailability of different phenolic compounds (from different plant extracts) through their interactions with blood proteins, cell membranes and DNA. Additionally, we would like to increase the bioavailability of phenolic compounds by encapsulation them into new delivery systems including archaeosomes; to investigate the effect of phenolic compounds on protein aggregations (involved into development of neurodegenerative diseases) and to study the structure-function relationship of thermally stable proteins.

Technological expertise: Besides standard physicochemical measurements (water activity, densitometry, viscosity, dielectric constants and conductivity), the antioxidative activity and polyphenolic compounds characterization, protein biochemistry and enzymology, we are equipped and trained to study the thermal stability of biological molecules by differential scanning calorimetry (DSC), fluorescence and UV-vis spectroscopy.

A few selected recent publications (2005-2010):

BERNE, Sabina, SEPČIĆ, Kristina, ANDERLUH, Gregor, TURK, Tom, MAČEK, Peter, POKLAR ULRIH, Nataša. Effect of pH on the pore forming activity and conformational stability of ostreolysin, a lipid raft-binding protein from the edible mushroom Pleurotus ostreatus. Biochemistry (Easton). [Print ed.], 2005, vol. 44, str. 11137-11147.

PAŠIĆ, Lejla, GALÁN BARTUAL, Sergio, POKLAR ULRIH, Nataša, GRABNAR, Miklavž, HERZOG-VELIKONJA, Blagajana. Diversity of halophilic archaea in the crystallizers of an Adriatic solar saltern. FEMS microbiol. ecol., 2005, vol. 54, str. 491-498.

POKLAR ULRIH, Nataša, SKRT, Mihaela, VERANIČ, Peter, GALVANI, Vesna, VRANAC, Tanja, ČURIN-ŠERBEC, Vladka. Oligomeric forms of peptide fragment PrP(214-226) in solution are preferentially recognized by PrPSc-specific antibody. Biochem. biophys. res. commun., 2006, vol. 344, str. 1320-1326.

POKLAR ULRIH, Nataša, LANIŠNIK-RIŽNER, Tea. Conformational stability of 17ß-hydroxysteroid dehydrogenase from the fungus Cochliobolus lunatus. FEBS journal, 2006, vol. 273, no. 17, str. 3927-3937.

POKLAR ULRIH, Nataša, ADAMLJE, Urška, NEMEC, Marjanca, ŠENTJURC, Marjeta. Temperature- and pH-induced structural changes in the membrane of the hyperthermophilic archaeon Aeropyrum pernix K1. J Membr Biol, 2007, issues 1/3, vol. 219, str. 1-8.

POKLAR ULRIH, Nataša, BARRY, Christopher H., FINK, Anthony L. Impact of Tyr to Ala mutations on [alpha]-synuclein fibrillation and structural properties. Biochim. biophys. acta, Mol. basis dis.. [Print ed.], 2008, issue 10, vol. 1782, str. 581-585.

POKLAR ULRIH, Nataša, OTA, Ajda, ŠENTJURC, Marjeta, KURE, Sandra, ABRAM, Veronika. Flavonoids and cell membrane fluidity. Food chem.. [Print ed.], 2010, issue 1, vol. 121, str. 78-84, doi: 10.1016/j.foodchem.2009.12.006.

OTA, Ajda, ABRAMOVIČ, Helena, ABRAM, Veronika, POKLAR ULRIH, Nataša. Interactions of p-coumaric, caffeic and ferulic acids and their styrenes with model lipid membranes. Food chem.. [Print ed.], 2011, vol. 125, issue 4, str. 1256-1261, doi: 10.1016/j.foodchem.2010.10.054.

Back to the top

Prof. Dr. Stojan Stavber

Affiliation: Laboratory of Organic and Bioorganic Chemistry, Department of Phisical and Organic Chemistry at Jožef Stefan Institute (, Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, Principal Investigator: Stojan Stavber

Keywords: green chemistry, halogenation, fluorination, organic reactions in water, aerobic oxidation

Research interest: Concern over environmental pollution, risks to human health and sustainable development has prompted chemists to search for more environmentally friendly methods to replace traditional ones. The concept of green chemistry emerged a decade ago and it has become increasingly important to apply such principles every area of science. Among some of the major challenges includes organic chemists reactions involving the principle of atom economy, efficient catalytic methodologies compared to stoichiometric reagents, suitability of a safer alternative reaction media (ionic liquids, fluorous liquids or water in place of volatile organic solvents, and reactions under solvent-free reaction conditions. Bearing this in mind, the programme of the group mainly deals with problems in "green organic chemistry" and “low carbon organic chemistry”. The main scope of our is the invention and development of chemical processes, which as much as possible mimic the analoque natural non-encimatic processes, are performed in aqueous or some other alternative media, and are leavig behind low waste. In one sentence: we are discovering and developing environmentally benign organic chemistry; organic chemistry for sustainable development.

Research goal: Halogenation of organic compounds in aqueous media is an open issue in the field of organohalogen chemistry requiring intensive research. In our continuing efforts we are investigating selective halogenation of organic compounds in aqueous media, with the special attention to oxidative halogenation, which is the most similar to analoque natural processes. As a source of halogen atoms halogenides are mainly be used, while air oxygen or aqueous hydrogen peroxide as biomimetics oxidants is applied. Our further investigations of the reactions of N-F reagents with organic compounds in aqueous media is performed. Aerobic and other biomimetic oxidation of organic compounds in water or under solvent-free conditions. Oxidation is one of the basic transformation of organic compounds and use of air oxygen or aqueous hydrogen peroxide for these reactions represents an eco-friendly protocol deminishing carbon content of overall process. The use of metalic (Ce(IV); Re(VIII); oxymetalates..) or no-metalic (NaNO2, HNO3, flavone...) catalysts are investigated for the use of aerobic oxidation of alcohols, aldehydes, ketones, and sulfides, in the later case also in a stereospecific way. Organic peroxides are important bioactive compounds as they release active oxygen species in the organism and thus generate radicals. Research is focused on structure/activity studies on antimalarial cyclic peroxides (1,2,4,5-tetraoxanes), while they poses also antiproliferative properties. Our continuing research in the field of organic peroxides is oriented into new synthetic methods for selective preparation of various classes of peroxides directly from carbonyl compounds and hydrogen peroxides.

Technological expertise: Organic synthesis of small molecules, halogenations of organic compounds, oxidative transformations of organic compounds, analysis of organic compounds using spectroscopic (NMR, MS, IR) and chromatographic techniques (GC, LC), mechanism of organic reactions.

A few selected recent publications:

Stavber, G.; Stavber, S. Toward Greener Fluorine Chemistry: Direct Electrophilic Fluorination of Carbonyl Compounds in Water and Under Solven-Free Reaction Conditions. Advanced Synthesis&Catalysis 2010, 352, 2838-2846.

Stavber, G.; Iskra, J.; Zupan, M.; Stavber, S. Aerobic oxidative iodination of ketones catalysed by sodium nitrite “on water” or in micelle-based aqueous system.Green Chem. 2009, 11, 1262-1267.

Stavber, G.; Zupan, M.; Stavber, S. Micellar-System-Mediated Direct Fluorination of ketones in water. Synlett 2009, 589-594.

Podgoršek, A.; Eissen, M.; Fleckenstein, J.; Stavber, S.; Zupan, M.; Iskra, J. Selective aerobic oxidative dibromination of alkenes with aqueous HBr and sodium nitrite as a catalyst. Green Chem. 2009, 11, 120-126.

Stavber, G.; Iskra, J.; Zupan, M.; Stavber, S. Aerobic oxidative iodination of organic compounds with iodide catalyzed by sodium nitrite. Adv. Synth. Catal. 2008, 350, 2921-2929.

Back to the top

Branko Jenko

Affiliation: Small R&D Co, Centre of excellence for integrated approaches in chemistry and biology of proteins, Principal Investigator: Branko Jenko

Keywords: semisynthetic new compounds, feeding compounds for chemobiosynthesis, API’s & impurities

Research interest: Our activities are mainly as follows : prepairing new methods for syntheses of generics or optimizing existing ones, including key intermediates. Synthesis or isolating of impurities and metabolites of API’s, synthesis of small molecules useful as feeding compunds in chemobiosynthesis. Our present acivity is semisynthesis of some interesting derivatives of natural products like resveratrole, (iso)flavonoids, sulforaphane etc.

We already have some preliminary results from screening tests, so far only on in vitro activity against prostate cancer cell cultures.

Research goal: Our goal is to prepaire few sets of semisynthetic derivatives and widen test range on other cell cultures to find some structure – activity relationship. We beleive this could lead us to choose some interesting molecule(s) for deep and detailed research because even starting natural compounds already showed some activity. In the field of chemobiosynthesis we intend to produce more feeding substances because this can lead to a huge range of new compunds which could be difficult if not impossible to obtain by the post biosynthesis chemistry.

Technological expertize: From our Labs and from previous engagement in other Co’s we have prepaired more than 20 new processes for synthesis of API’s, covered with some 30 patents. Our list of new semisynthetic substances now counts 11 and is growing. We have prepaired also 4 new feeding substances for chemobiosynthesis. One of them already showed a successful producing a new macrolide lactone.


Patents (30): link1, link2
Others :

JENKO, Branko, STANOVNIK, Branko, TIŠLER, Miha. Synthesis of s-triazolo[1,5-c]pyrimidine. Synthesis (Stuttg.), December 1976, no. 12, str. 833-836, graf. prikazi. [COBISS.SI-ID 19615749]

ŽMITEK, Janko, JENKO, B..., KOŠAK, Alenka, MILIVOJEVIČ, Dušan. The synthesis of some guanidine derivatives. Org. prep. proced. int., 1985, let. 17, str. 156. [COBISS.SI-ID 49602]

ŽMITEK, Janko, JENKO, B..., MILIVOJEVIČ, Dušan, ANŽEL, J.... The synthesis and reactions of N-Cyano-O-methylpseudoureas. Org. prep. proced. int. , 1991, let. 23, št. 6, str. 721-728. [COBISS.SI-ID 50114]

MILIVOJEVIČ, Dušan, ŽORŽ, Mirjan, ŽMITEK, Janko, HRIBAR KIKELJ, Alenka, KOŠAK, Alenka, JENKO, B.... Analytical approach to the synthesis of 4-methyl imidazole and its derivatives. V: 9th International Symposium on Column Liquid Chromatography, 1985, Edinburg. [S.l.]: [s.n.], 1985. [COBISS.SI-ID 55746]

ŽMITEK, Janko, JENKO, Branko . A new method for the preparation of N-cyano-N'- methyl-N"-(2-haloethyl) guanidine : japonski patent JP 1689379; jugoslovanski patent št. 43660, registracija v Sloveniji SI št. 8312151 . 1983. [COBISS.SI-ID 2344986]

HUMLJAN, Jan, STARČEVIĆ, Štefan, CAR, Vjekoslava, ŠTEFANIČ, Petra, KOCJAN, Darko, JENKO, Branko, URLEB, Uroš. Optimization of UDP-N-acetylmuramic acid synthesis. Pharmazie, 2008, vol. 63, no. 2, str. 102-106. [COBISS.SI-ID 2248817]

Back to the top

Prof. Dr. Ana Plemenitaš

Affiliation: University of Ljubljana, Faculty of Medicine, Institute of Biochemistry; Member of Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, Principal Investigator: Ana Plemenitaš;

Keywords: halophily, fungi, mechanisms of osmo-adaptation, HOG signaling pathway, molecular determinants of halotolerance

Research interest: Our long term interest is to understand the mechanisms important for adaptation of fungi to high salt concentrations in the environment. To this goal, we study organisms that are salt-tolerant by nature on a cellular and molecular level. We are particularly interested in the HOG signaling pathway, which senses and responds to the increased environmental osmolarity by regulating the expression of target genes.

Research goal: Our primary goal is to identify and characterize key genes and their products important for organism’s halotolerance. Towards this goal we perform gene-specific and whole-organism studies on a cellular, proteome, transcriptome and genome level. We use two model organisms: extremely halotolerant black yeast Hortaea werneckii and halophilic fungi Wallemia ichthyophaga, both isolated from Sečovlje salterns. Our ultimate goal is the genetic manipulation of crops by including individual transgenes from halotolerant fungal species in order to produce improvement in plant halotolerance. The improved crops would be of great value, especially in the underdeveloped countries, where salt stress is becoming a threat to the agriculture due to irrigation of many productive areas.

Technological expertise: general biochemistry and molecular biology techniques; culturing and handling of yeasts and extremophilic fungi; fungal genomics, transcriptomics and proteomics

A few publications:

PETROVIČ, Uroš, GUNDE-CIMERMAN, Nina, PLEMENITAŠ, Ana. Cellular responses to environmental salinity in the halophilic black yeast Hortaea werneckii. Mol. microbiol., 2002, 45, 665-672.

LENASSI, Metka, PLEMENITAŠ, Ana. Novel group VII histidine kinase HwHhk7B from the halophilic fungi Hortaea werneckii has a putative role in osmosensing. Curr Genet, 2007, 51(6), 393-405.

VAUPOTIČ, Tomaž, PLEMENITAŠ, Ana. Differential gene expression and Hog1 interaction with osmoresponsive genes in the extremely halotolerant black yeast Hortaea werneckii. BMC Genomics, 2007, 8(1), 280.

VAUPOTIČ, Tomaž, GUNDE-CIMERMAN, Nina, PLEMENITAŠ, Ana. Novel 3'-phosphoadenosine-5'-phosphatases from extremely halotolerant Hortaea werneckii reveal insight into molecular determinants of salt tolerance of black yeasts. Fungal genet. biol. (Print), 2007, 44(11), 1109-1122.

PLEMENITAŠ, Ana, VAUPOTIČ, Tomaž, LENASSI, Metka, KOGEJ, Tina, GUNDE-CIMERMAN, Nina. Adaptation of extremely halotolerant black yeast Hortaea werneckii to increased osmolarity : a molecular perspective at a glance. Stud. Mycol., 2008, letn. 61, str. 67-75.

Back to the top