Institute of Biochemistry is a research centre focusing on investigation of biochemical and genetic principles of cell functioning - genetic engineering, biocatalysis, signaling and cell regulation, basic and applied aspects of enzyme chemistry, biosensor design, synthesis of the organic compounds.
The staff of the Institute consists of experienced, qualified and competent more than 50 scientists, 30 doctoral students with expertise in the field of biochemistry, microbiology, cellular biology and chemistry.
The Institute of Biochemistry operates at the interface between medicine, biology and chemistry to investigate the structure and function of cells, biomolecules, (bio)materials.
Institute provides infrastructure for postgraduate studies leading to Masters and PhD qualifications.
Main R&D activities
Investigation and application of biocatalysts and self-assembling structures
- Screening, development and application of biocatalysts
- Metabolic pathways in microorganisms
- Genetic diversity and molecular biology of bacteria and bacteriophages
- Metabolism of modified nucleotides and nucleosides
- Self-assembling lipid systems and their interactions with proteins
- Investigation of the electron transport in proteins, the structure and functioning of enzymes
- Development and investigation of bioelectrocatalytical systems for biosensors and bioreactors
- Synthesis, biochemical characterization and cytotoxicity studies of redox active xenobiotics and other organic compounds
- Search and development for methods of synthesis of bioorganic compounds as modulators of biologic processes
Signaling pathways and epigenetic regulation of tumor and stem cells
- Studies of the molecular mechanisms of signal transduction in normal and cancer cells
- Epigenetic regulation in cancer and stem cells
- High-throughput proteomics analysis of cell signaling
- Elucidation of artificial microstructures and nano-particles on cell functioning
- Adult stem cells properties and their sensitivity in vitro and in vivo
- Cell technologies for the regenerative medicine: development and evaluation using biological models
Research services
Screening of novel enzymes for biocatalysis
- Biodiversity of catabolic pathways.
- Screening and development of enzymes including metagenomic libraries and genetic engineering.
- Application of enzymes for bioconversion and biosensors.
- Understanding of the genetics, biochemistry and mechanisms of biodegradation of various N-heterocycles (hydroxy-, methyl- and carboxypyridines and pyrazines) and development of biocatalytic processes for conversion of glycerol, starch and other carbohydrates.
Protein analysis and their sub-subcellular localization
- Protein identification, purity and stability analysis.
- Peptide de novo sequencing.
- Protein-protein complex formation (dimerization, oligomerization, etc.) analysis.
- Identification of protein chemical modification (cell signaling).
- Proteome differential screening (marker discovery).
- Hypothesis-driven protein analysis (marker verification).
- Protein co-localization in cells (study of protein function).
Cell technologies
- Microinjection of proteins and other substances into the live cell to study their function.
- Screening of novel chemical compounds for potential therapeutic activity.
- Studies of cytotoxicity.
- Cellular microenvironment modeling in vitro.
- Construction and testing of scaffolds designed for regenerative medicine.
- Fabrication of artificial tissues.
In vivo testing
- Preclinical studies of novel materials and chemical compounds: acute and repeated dose toxicity tests (oral, dermal, skin irritation, eye irritation, skin sensitization).
- Biocompatibility tests in vivo.
Biosensors design
- Bioanalytical systems for food-quality control, medicine, environment.
- Determination of enzymes and metabolites in food-stuffs, blood, microbiological liquids.
Synthesis of organic compounds
- Investigation of synthesis methods for organic compounds of different classes
- Design and development of technology of chemical processes for commerce and industry
Head dr. Marius Dagys Research interests Investigation of bioelectrochemical properties of biomolecules Investigation of electron transport in biomolecules Creation of biosensors and bioreactors Investigation of the mechanism of action of biomolecules and cells in heterogeneous systems and mathematical modeling. Whole-cell biosensors, bacterial self-organization, biofilms. RESEARCH OWEREVIEW 2012-2017 Specially prepared carbon materials can possess direct electrochemical communication with redox centers of some redox proteins. For this reason a few types of graphite nanoparticles have been manufactured by oxidation of graphite using different protocols and characterized by AFM, Raman spectroscopy, TGA and BET analysis. Also thermally reduced graphene oxides and nanocomposite materials have been prepared and studied. Different oxidoreductases were applied and demonstrated direct electron transport between surface of the carbon materials and active center of the enzyme. These structures were applied in different technological structures. One of them - creation of mediatorless bio-anodes and bio-cathodes for bio-solar cells, bio-batteries and bio-fuel cells. Second direction -the same structures were applied for the creation of new type of biosensors for the determination of the sugars and alcohols. Carbon materials were applied for the electrochemical monitoring of urease activity and electrochemical biosensors for urea were developed. These biosensors were applied in medicine, environment control, and for the quality control in food industry. In this field the project „Non- invasive approach to early diagnosis and prognosis of acute severe pancreatitis (AP)” was recently funded. The ambitiousness of the project is to diminish lack of information causing AP diagnostic, prognostic and followed treatment problems by deep understanding of AP biochemical processes that could help to create new diagnostic tools. Beekeeping products conserved with honey were analyzed. Monitoring of the changes of parameters of the mixtures via different storage conditions revealed a stabilizing influence of honey and additives on anti-oxidative properties, composition of flavonoids and activity of the enzymes of the mixtures. The numerical mathematical modelling of heterogeneous bio-electro-catalytic systems made possible to determine several structural and kinetic parameters of the sensor and bioreactor construction. Bioluminescence imaging experiments were carried out to characterize spatiotemporal patterns of self-organization of bioluminescent E. coli and its mutants in standard microtiter plates. An analysis of the effects of mutations shows that spatiotemporal patterns formed due to migration (swimming) of cells near three phase contact line are not related to the chemotaxis system of bacteria. An analysis of experimental data and mathematical modelling of pattern formation indicate that pattern-forming active bacteria can be interpreted as self-phoretic cells dispersed in a liquid suspension. National Research Projects Research Council of Lithuania Self-organization of E. coli and their mutants near three phase contact line. (2014-2016) Dr. R. Šimkus. Bee products enriched with plant components, the composition and properties. (2012-2015) Dr. B. Kurtinaitiene. Biotechnology and Biopharmacy: fundamental and applied research, activity 1.1.4. (2012-2015) Head of the Action Dr. J. Razumiene. Non- invasive approach to early diagnosis and prognosis of acute severe pancreatitis (AP). (2017-2021) Dr. J. Razumiene. Lithuanian Agency for Science, Innovation and Technology. EUREKA Project E! 8835. Multiple biosensor device for hemodialysis patients. (2014-2016) Dr. J. Razumiene. Development of carbamide analyser for measurements in industrial media (2017 – 2018) Dr. J. Razumienė High technology development program “Search of new and genetically modified oxidoreductases for creation of biofuel cells (BIOFUELCELL), (2011-2013). Coordinator – JSC “Lithuanian Research Centre”, manager – dr. Marius Dagys. International Research Projects 7 FW Leonardo da Vici Program. „Food Industry - Food Legislation, Impact Analysis, Training and Cooperation Network in Europe -E-Learning“ (2012-2014). Prof. V. Laurinavicius. COST CM0701 “Cascade Chemoenzymatic Processes – New Synergies Between Chemistry and Biochemistry“ (CASCAT). (2010-2014) Dr. J. Razumiene. Contractual Research Foundation of dr. Bronislovas Lubys. Applied Charity and Support.“Amperometric fast response method for measurement of urea concentration in industrial media”.(2015 – 2016) dr. Marius Dagys. Main publications: Razumiene J., Gureviciene V., Sakinyte I., Barkauskas J., Petrauskas K.,. Baronas R. Modified SWCNTs for Reagentless Glucose Biosensor: Electrochemical and Mathematical Characterization. Electroanalysis. 2012, Vol. 24, p. 1- 8. Misiūnas A., Niaura G., Barauskas J., Meškys R., Rutkienė R., Razumas V., Nylander T. Horse heart cytochrome c entrapped into the hydrated liquid-crystalline phases of phytantriol: X-ray diffraction and Raman spectroscopic characterization. Journal of Colloid and Interface Science. 2012, Vol. 378, p. 232-240. Penkauskas T, Preta G. (2019): Biological applications of tethered bilayer lipid membranes. Biochimie. Nov 22;157:131-14 Santos A.L., Preta G. (2018): Lipids in the cell: organization regulates function. Cell Mol Life Sci.. Jun;75(11):1909-1927. Griffin S, Preta G., Sheldon IM. (2017): Inhibiting mevalonate pathway enzymes increases stromal cell resilience to a cholesterol-dependent cytolysin. Sci. Rep. Dec 6;7(1):17050. Baronas R., Kulys J., Petrauskas K., Razumiene J. Modelling Carbon Nanotubes-Based Mediatorless Biosensor. Sensors. 2012, Vol. 12, No. 7, p. 9146-9160. Simelevicius D., Baronas R., Kulys J. Modelling of Amperometric Biosensor Used for Synergistic Substrates Determination. Sensors. 2012, Vol. 12, No 4, p. 4897-4917. Kulys J., Bratkovskaja I. Glucose Dehydrogenase Based Bioelectrode Utilizing a Synergistic Scheme of Substrate Conversion. Electroanalysis. 2012, Vol. 24, No 2, p. 273-277.7.Laurinavicius V., Razumiene J., Gureviciene V. Bio-electrochemical Conversion of Urea on Carbon Black Electrode and Application. IEEE Sensors. 2013, Vol. 13, No. 6, p. 2208-2213. Ašeris V., Baronas R., Kulys J. Modelling the biosensor utilising parallel substrates conversion. Journal of Electroanalytical Chemistry. 2012, Vol. 685, p. 63–71. Kulys J., Bratkovskaja I., Ašeris V., Baronas R. Electrochemical Peroxidase-Catalase Clark-Type Biosensor: Computed and Experimental Response. Electroanalysis. 2013, Vol. 25, No. 6, 1491 – 1496. Tetianec L., Chaleckaja A., Vidžiūnaitė R., Kulys J., Bachmatova I., Marcinkevičienė L., Meškys R. Development of a laccase/syringaldazine system for NAD(P)H oxidation. Journal of Molecular Catalysis. B: Enzymatic. Amsterdam: Elsevier. 2014, Vol. 101, p. 28-34. Dagys M., Lamberg P., Shleev S., Niaura G., Kulys J., Arnebrant Th., Ruzgas T., Comparison of bioelectrocatalysis at Trichaptum abietinum and Trametes hirsuta laccase modified electrodes. Electrochimica Acta. Oxford : Pergamon-Elsevier Ltd. 2014, Vol. 130, p. 141-147. Ivanauskas F., Katauskis P., Laurinavičius V. Mathematical modeling of biosensor action in the region between diffusion and kinetic modes. Journal of Mathematical Chemistry. 2014, Vol. 52, p. 689-702. Simelevicius D., Petrauskas K., Baronas R., Razumiene J. Computational Modelling of Mediator Oxidation by Oxygen in Amperometric Glucose Biosensor. Sensors. 2014, Vol. 14, No. 2, p. 2578-2594. Snopok B., Naumenko D., Servienė E., Bružaitė I., Stogrin , Kulys J., Snitka V., Evanescent-field-induced Raman scattering for bio-friendly fingerprinting at sub-cellular dimension. Talanta. Amsterdam: Elsevier Science. 2014, vol. 128, p. 414-421. Barkauskas J., Dakševič J., Budrienė S., Razumienė J., Šakinytė I. Adhesion of graphene oxide on a transparent PET substrate: a study focused on the optimization process. Journal of Adhesion Science and Technology. 2014, Vol. 28, No. 20, 2016-2031. Razumiene J., Sakinyte I., Barkauskas J., Baronas R. Nano-structured carbon materials for improved biosensing applications. Applied Surface Science. 2015, Vol. 334, p. 185-191. Razumiene J., Cirbaite E., Razumas V., Laurinavicius V. New mediators for biosensors based on PQQ-dependent alcohol dehydrogenases. Sensors and Actuators B: Chemical. 2015, 207, p. 1019-1025. Ratautas D., Marcinkevičienė L., Meškys R., Kulys J. Mediatorless electron transfer in glucose dehydrogenase/laccase system adsorbed on carbon nanotubes. Electrochimica Acta. 2015, Vol. 174, p. 940-944. Ratautas D., Laurynėnas A., Dagys M., Marcinkevičienė L., Meškys R., Kulys J. High current, low redox potential mediatorless bioanode based on gold nanoparticles and glucose dehydrogenase from Ewingella Americana. Electrochimica Acta. 2016, Vol. 199, p. 254-260. Ivanauskas F., Katauskis P., Laurinavicius V. Impact of convective transport and inert membrane on action of bio-catalytic filtre. Journal of Mathematical Chemistry. 2016, 54, (6), p. 1221-1232. Šimkus R., Meškienė R., Ledas Ž., Baronas R., Meškys R. Microtiter plate tests for segregation of bioluminescent bacteria. Luminescence. 2016, Vol. 31, No 1, p. 127-134. Dagys M., Laurynėnas A., Ratautas D., Kulys J., Vidžiūnaitė R., Talaikis M., Niaura G., Marcinkevičienė L., Meškys R., Shleev S. Oxygen electroreduction catalysed by laccase wired to gold nanoparticles via the trinuclear copper cluster. Energy & Environmental Science , 2017, Vol. 10, p. 498-502. Tetianec L., Chaleckaja A., Kulys J., Janciene R., Marcinkeviciene L., Meskiene R., Stankeviciute J., Meskys R. Characterization of methylated azopyridine as a potential electron transfer mediator for electroenzymatic systems. Process Biochemistry. 2017, Vol. 54, p. 41-48. Ratautas D.,Tetianec L., Marcinkevičienė L., Meškys R., Kulys J. Bioanode with alcohol dehydrogenase undergoing a direct electron transfer on functionalized gold nanoparticles for an application in biofuel cells for glycerol conversion. Biosensors Bioelectronics. 2017, Vol. 98, p. 215-221. Gaidukevic J., Razumiene J., Sakinyte I., Rebelo S. L.H., Barkauskas J.. Study on the structure and electrocatalytic activity of graphene-based nanocomposite materials containing (SCN)n. Carbon. 2017, Vol. 118, p. 156 – 167. MAIN R&D&I (RESEARCH, DEVELOPMENT AND INOVATION) PARTNERS VGTU (Lithuania), Malmo University (Sweeden), Institute of Molecular Biology and Genetics of the National Academy of Science of Ukraine, UAB Bioanalizės sistemos, UAB Ubique calculus, UAB Sentiero Baltic. Head dr. Gintaras Valinčius Formation of plasma membrane is considered as a crucial event during evolution and life, as known today, would not be possible without them. Actual plasma membranes contain a complex, heterogeneous distribution of lipids and membrane proteins which interact to create important biological functions. To investigate this complex membrane environment significant progress has been made to model native membranes. Our research group focuses on development of nature inspired models, in particular, surface tethered phospholipid membranes (tBLM) and membrane-protein complexes exhibiting catalytic activities. The group addresses problems related to basic life-science as well as applications in biomedicine. In particular, including sensor development for various endogenous and exogenous pathogens and ultrasensitive detection of microbial toxins (α-hemolysin (αHL), Vaginolysin (VLY), Pneumolysin (PLY), etc.). We offer a broad spectrum of technological solutions to reconstitute proteins into the tethered bilayer for structural and functional studies. Bioelectrochemical and Biospectroscopic techniques and relevant expertise can be accessed by the external users through the standard open access procedures implemented at Vilnius University. We seek both academic and industrial partnerships to further develop molecular devices based on tethered bilayer technologies and advance basic knowledge in the field of the protein function in biological membranes. In particular, we seek to establish partnerships with theoretical groups having expertise in modelling structures of biomolecules in membranes as well as predicting the dynamic properties of ion carriers in confined nano-compartments. Also, we aim to spread our technological knowledge into the areas of biochemistry and molecular biology where the phospholipid milieu is required for functional reconstitution of membrane proteins for structural and functional studies. Joint initiatives for EU and other international funding for research and technology development are also sought-after. Main Grants (2007–2017): Main Publications (2007–2019): Dagys M., A. Laurynėnas, D. Ratautas J. Kulys, R. Vidžiūnaitė, M. Talaikis, G. Niaura, L. Marcinkevičienė, R. Meškys, Shleev. 2017. Oxygen electroreduction catalysed by laccase wired to gold nanoparticle via trinuclear copper cluster. Energy&Environmental Science 10: 498-502 Preta G. Understanding the Dr. Jekyll and Mr. Hyde nature of apoptosis-inducing factor: future perspectives. Biomedical Journal 40: 239-240; Penkauskas T, Preta G. (2019): Biological applications of tethered bilayer lipid membranes. Biochimie. Nov 22;157:131-14 Santos A.L., Preta G. (2018): Lipids in the cell: organization regulates function. Cell Mol Life Sci.. Jun;75(11):1909-1927. Griffin S, Preta G., Sheldon IM. (2017): Inhibiting mevalonate pathway enzymes increases stromal cell resilience to a cholesterol-dependent cytolysin. Sci. Rep. Dec 6;7(1):17050. Valiuniene, T.Petrulioniene, I.Baleviciutei, L.Mikoliunaite, G.Valincius. Formation of hybrid bilayers on silanized thin-film Ti electrode. Chemistry and Physics of Lipids. 2017, 202, 62-68. Ragaliauskas T., M. Mickevičius, B. Rakovska, T. Penkauskas,J. Vanderah, F.Heinrich,G. Valinčius. 2017. Fast formation of low-defect-density tethered bilayers by fusion of multilamellar vesicles. Biochimica et Biophysica Acta (BBA) - Biomembranes 1859: 669-678. Eicher-Lorka O., T. Charkova, A. Matijoska, Z. Kuodis, G. Urbelis, T. Penkauskas, M. Mickevičius, A. Bulovas, G. Valinčius. 2016. Cholesterol-based tethers and markers for model membranes investigation. Chemistry and Physics of Lipids 195: 71-86. Preta G., M. Jankunec, F. Heinrich, S. Griffin, I.M. Sheldon, G. Valinčius. 2016. Tethered bilayer membranes as a complementary tool for functional and structural studies: The pyolysin case. Biochimica et Biophysica Acta-Biomembranes 1858: 2070-2080. Talaikis M., O. Eicher-Lorka, G. Valinčius, G. Niaura. 2016. Water-Induced Structural Changes in the Membrane-Anchoring Monolayers Revealed by Isotope-Edited SERS. Journal of Physical Chemistry C 120: 22489-22499 Valinčius G., M. Mickevičius, T. Penkauskas, M. Jankunec. 2016. Electrochemical Impedance Spectroscopy of Tethered Bilayer Membranes: An Effect of Heterogeneous Distribution of Defects in Membranes. Electrochimica Acta 222: 904-913. Rakovska B., T. Ragaliauskas, M. Mickevičius, M. Jankunec, G. Niaura, D.J. Vanderah, G. Valinčius. 2015. Structure and function of the membrane anchoring self-assembled monolayers. Langmuir 31: 846-857. Ragaliauskas T., M. Mickevičius, R. Budvytytė, G. Niaura, B. Carbonnier, G. Valinčius. 2014. Adsorption of b-amyloid oligomers on octadecanethiol monolayers. Journal of Colloid and Interface Science 425: 159-167. Budvytytė R., M. Mickevičius, D.J. Vanderah, F. Heinrich, G. Valinčius. 2013. Modification of tethered bilayers by phospholipid exchange with vesicles. Langmuir 29: 4320-4327. Budvytytė R., M. Plečkaitytė, A. Žvirblienė, D. J. Vanderah, G. Valinčius. 2013. Reconstitution of cholesterol-dependent vaginolysin into tethered phospholipid bilayers: implications for bioanalysis. PLOS ONE. 8: e82536. Budvytytė R., G. Valinčius, G. Niaura, V. Voiciuk, M. Mickevičius, H. Chapman, H.Z. Goh, P. Shekhar, F. Heinrich, S. Shenoy, M. Losche, D.J. Vanderah. 2013. Structure and properties of tethered bilayer lipid membranes with unsaturated anchor molecules. Langmuir 29: 8645-8656. Valincius G., T. Meskauskas, F. Ivanauskas. 2012. Electrochemical impedance spectroscopy of tethered bilayer membranes. Langmuir 28: 977-990. Voiciuk V., G. Valincius, R. Budvytyte, A. Matijoska, I. Matulaitiene, G. Niaura. 2012. Surface-enhanced Raman spectroscopy for detection of toxic amyloid beta oligomers adsorbed on self-assembled monolayers. Spectrochimica Acta Part A-molecular and Biomolecular Spectroscopy 95: 526-532. Cizas P., R. Budvytyte, R. Morkuniene, R. Moldovan, M. Broccio, M. Loesche, G. Niaura, G. Valincius, V. Borutaite. 2010. Size-dependent neurotoxicity of beta-amyloid oligomers Archives of Biochemistry and Biophysics 496:84-92. K. J. Kwak, G. Valincius, W.-C. Liao, X. Hu, X. Wen, A. Lee, B. Yu, D. J. Vanderah, W. Lu and L. J. Lee. 2010. Formation and finite element analysis of tethered bilayer lipid structures. Langmuir 26:18199-18208. McGillivray D., G. Valincius, F. Heinrich, J. Robertson, D. Vanderah, W. Febo-Ayala, I. Ignatjev, M. Lösche, J. Kasianowicz. 2009. Structure of functional Staphylococcus aureus alpha-hemolysin channels in tethered bilayer lipid membranes. Biophysical Journal 96: 1547-1553. Kazakevičienė, B., G. Valinčius, M. Kažemėkaitė, V. Razumas. 2008. Self-assembled redox system for bioelectrocatalytic assay of L-ascorbylphosphate and alkaline phosphatase activity. Electroanalysis 20: 2235-2240. Valincius, G., F. Heinrich, R. Budvytyte, D.J. Vanderah, Y. Sokolov, J.E. Hall, M. Loesche. 2008. Soluble amyloid ß oligomers affect dielectric membrane properties by bilayer insertion and domain formation: Implications for cell toxicity. Biophysical Journal 95: 4845-4861. McGillivray, D. J., G. Valinčius, D. J. Vanderah, W. Febo-Ayala, J. T. Woodward, F. Heinrich, J. Kasianowicz, M. Losche. 2007. Molecular-scale structural and functional characterization of sparsely tethered bilayer membranes. Biointerphases 2: 21-33 Collaborations: Long-term projects with research groups at the Institute for Biotechnology and Bioscience Research at the University of Maryland (College Park, USA), Carnegie Mellon University (USA) and NIST Center for Neutron Research (USA), Niels Bohr Institute at University of Copenhagen (Denmark). Swansea University, Wales, UK: biological and biophysical approaches for the characterization of the cholesterol-dependent cytolysins Pyolysin (PLO). Haifa University, Israel: using biophysical approaches (EIS and AFM) to study the structure and function of the pro-apoptotic protein BAX. Malmö University, Sweden: prof. Johan Engblom. Dermal Drug Delivery - Increasing bioavailability in viable skin. Head dr. Virginija Bukelskienė The Department of Biological Models focuses on the study of adult stem cells and their application for regenerative medicine using two model systems - in vitro (cell cultures) and in vivo (experimental animals). The team has deep knowledge of artificial tissue construction, using polymer scaffolds. Their expertise includes the evaluation of material biocompatibility, cell-surface interactions and methods of stem cell differentiation and associated processes assessment. The ultimate goal of these studies is to control the behavior of stem cells, directing them towards specific lineage differentiation by tailoring the chemical composition, physical properties and surface coating of the materials. Fabricated segments of artificial tissues are tested in vivo – by surgical implantation in animals. The department has a modern laboratory for experimental animals, which is designed for work with mice, rats and rabbits. The animals are kept either in conventional or SPF (specific-pathogen-free) areas. The laboratory is approved by the State Food and Veterinary Service for breeding and selling as well as experimental work with animals. The highly qualified staff hold all the necessary certificates for animal research. Some facilities, including a fully equipped operating room and laboratory for working with animal specimens are open to all scientists who have the right to work with animals. In this laboratory, heart failure research is carried out, studies of biocompatibility and toxicological tests are being performed. Projects 2012-2017: Main publications 2012-2017: Head prof. Rūta Navakauskienė Research interests We study the molecular mechanisms of normal, cancer and stem cells functioning in order to determine new possibilities in cancer therapy and regenerative medicine. Studies are designed to predict the outcome of treatment in in vitro models and in the individual cases (Personalized Cancer Therapy): Research resources and services/Offer Cancer and stem cell culturing (isolation, cultivation, differentiation), Flow cytometry analysis (sample preparation and analysis, cell cycle checkpoints), Protein fractionation one or two dimensional electrophoresis (SDS/PAGE and 2DE, further preparation for mass spectrometry analysis), Real-time PCR analysis, Epigenetic markers (histone modifications, DNA methylation), Chromatin immunoprecipitation (sonication, ChIP and PCR), Microscopy, Cytoxicity evaluation and signaling mechanisms determination in cellular models. Research projects 2012-2017 Project Supported by University Budget Studies of regulatory mechanisms of cancer and stem cell for new technologies of personalized medicine. Prof. R. Navakauskienė. 2014-2018. Projects Supported by Research Council of Lithuania (2012-2017): National Science program project „Multiplexed molecular biomarker study for leukemia“ (No. LIG-06-2012) Prof. Rūta Navakauskienė. 2012-2014 National Science program project “Bee products enriched with plant components, the composition and properties”(No. SVE-01/2012) Dr. Bogumila Kurtinaitienė. 2012-2015 “Cytological, molecular and epigenetic studies of amniotic fluid” (No. MIP-033/2013) Dr. Gražina Treigytė. 2013-2015 National Science program project “The role of molecular modulators in the hematological system during cell senescence, differentiation and regeneration” (No. SEN-12/2015) Prof. Rūta Navakauskienė. 2015–2018. “Regulation of amniotic fluid‐derived stem cell functioning by microRNA and epigenetic factors” (No. MIP-57/2015) Dr. Jūratė Savickienė. 2015-2018. Projects Supported by EU funding: ”Molecular processes in eukaryotic cells: technological and medical aspects”, 2012-2015, funded by the EU support program „Biotechnology and biopharmacy: fundamental and applied research“. Head prof. R. Navakauskienė. ”Molecular mechanisms of the toxicity and antitumor activity of quinones and polyphenols: enzymatic redox reactions, cytotoxicity, signal transduction and proteomics“. 2011-2015, funded via the Global Grant measure, managed using EU funding. Head habil. dr. N. Čėnas. International Research Projects (2012-2017): CM1106 Chemical approaches to targeting drug resistance in cancer stem cells (StemChem). Prof. R. Navakauskienė. 2011-2015 BM1402 Development of a European network for preclinical testing of interventions in mouse models of age and age-related diseases (MouseAGE). Prof. R. Navakauskienė. 2014-2018. CA15138 European Network of Multidisciplinary Research and Translation of Autophagy knowledge (TRANSAUTOPHAGY). Dr. Veronika Borutinskaitė. 2015- 2019. MAIN R&D&I (RESEARCH, DEVELOPMENT AND INOVATION) PARTNERS Vilnius Gediminas Technical University, Linkoping University (Sweden), Nice University (France), Milan University (Italy), Malta University (Malta), Northwestern University (USA) Main publications (2012-2017): Head dr. Rolandas Meškys Microbial diversity both genetic and biochemical is incredible resource of different proteins and biocatalysts. Analysis and exploration of such diversity is one of the main aim of our group. The studies are concentrated in several fields. The first one is related to isolation of N-heterocyclic compounds-utilising microorganisms and investigation of catabolic pathways of these compounds in individual bacteria. Both genetic and biochemical characterization of bioconversion processes are carried out. The identified novel oxygenases as well as other enzymes participating in the biodegradation are tested as biocatalysts for organic chemistry. The modified nucleotides are ones of the many substrates, whose catabolism is being elucidated. In addition, the studies of biosynthetic pathways of wyosine, a modified nucleotide base, is also our activity. Screening of novel enzymes is also carried out by application of metagenomic techniques, specific and effective selection systems combined with tailored substrates. In cooperation with other groups both from Vilnius University and international, the screened enzymes are used for development of biosensors, biofuel-cells and for synthesis of industry-related chemical compounds. The second major field of our activities is associated with studies of bacteriophages active towards various gram-negative and gram-positive bacteria. We are interested in elucidation of structural diversity of bacteriophages, initial stages of the infection process and the identification of self-assembling proteins applicable for construction of the hybrid nanoparticles. We are experts in discovering of enzymes including hydrolases, oxidoreductases and transaminases. Metagenomic libraries combined with the “smart” substrates that are developed and synthesized in our group is a technology, which offers an efficient screening and selection of novel biocatalysts applicable for bioconversion, organic syntheses and development of biosensors as well as biofuel cells. Our team is also skilled in isolation and identification of bacteriophages as a source of proteins predisposed to form self-assembling structures and important for the biomedical application. Key grants (2012–2017): National Research Projects funded by Research Council of Lithuania: Development of methods for screening and expression of Baeyer-Villiger monooxygenases. (MIP-042/2012) Dr. R. Meškys. 2012–2014. tRNA modification pathways – evidence of the enzyme evolution. (MIP-043/2012) Dr. J. Urbonavičius. 2012–2014. European Social Fund (ESF) under the Human Resources Development Action Programme, the Global Grant measure, project No. VP1-3.1-ŠMM-07-K-03-015. Change or die: redesign of oxidoreductases (CHORD). Dr. R. Meškys. 2013–2015. Proteogenomics of the early infection stages of virulent Escherichia coli bacteriophages. (MIP-002/2014) Dr. L. Truncaitė. 2014–2016. Screening and analysis of novel enzymes participating in catabolism of modified uracil base and nucleosides (MIP-103/2015) Dr. J. Urbonavičius. 2015–2017. Novel prodrug activation systems for cancer genotherapy (SEN-15027) Dr. J. Urbonavičius. 2015–2018. International Research Projects: EU Horizon2020 Program. H2020-BG-2014-2. Industrial Applications of Marine Enzymes: Innovative screening and expression platforms to discover and use the functional protein diversity from the sea (INMARE). Dr. R. Meškys. 2015–2019. Contractual Research: Bayer Technology Services GmbH (Germany), Amilina AB (Lithuania), Baxalta Innovation GmbH (Austria). Dr. R. Meškys. Key publications (2012–2017): Head habil. dr. Narimantas Čėnas Main research directions. Synthesis of prooxidant xenobiotics (quinones, aromatic nitrocompounds, N-oxides, etc.), studies of interaction of these compounds with flavoenzymes and their impact on their cytotoxicity, mechanisms of flavoenzyme catalysis, prooxidant cytotoxicity of polyphenolic compounds. Since 1992, the Department collaborates with research centers in Lithuania, Belarus, Great Britain, Spain, Italy, USA, New Zealand, the Netherlands, France, Sweden, and Ukraine. We have participated in projects supported by the EC (2), NATO (2), the Royal Swedish Academy of Sciences (1), bilateral projects with France (2), Belarus (1), and Ukraine (1), COST actions (4), received a number of grants from LSSSF and RCL including the project funded by European Social Fund (ESF) under the Human Resources Development Action Programme, the Global Grant measure (2011-2015). Synthesis of prooxidant compounds. We have synthesized or resynthesized over 300 compounds of different groups – nitroaromatic and nitroheterocyclic compounds, aliphatic nitrates, aromatic N-oxides, quinones, benzofuroxans, etc. (Fig. 1), examined their electrochemical properties and characterized their reduction energetics by quantum-mechanical methods. Fig. 1. High-energy substances tetryl (1), keto-RDX (2), PETN (3), and other groups of compounds: nitrobenzimidazolonesi (4), aziridinyl-substituted quinones (5) and nitrobenzenes (6), nitrofurans (7), benzofuroxanes (8), di-N-oxides of quinoxaline (9) and 1,2,4-benzotriazine (10), and heterocyclic oximes (11). The mechanisms of single- and two-electron reduction of quinones, nitroaromatic compounds, and other prooxidants by flavoenzymes. Flavoenzymes electrontransferases reduce quinones, aromatic nitrocompounds and N-oxides into their free radicals. The latter are reoxidized by oxygen with the formation of superoxide and other reactive oxygen species (ROS) causing the oxidative stress which significantly determines their cytotoxicity , antitumour and other therapeutic activity of the compounds. The enzymatic single-electron reduction reactions of the compounds have been examined applying mammalian cytochrome P-450 reductase, NO-synthase (in collaboration with J.-L. Boucher, Universite de Paris V), Anabaena sp. and P. falciparum ferredoxin:NADP+ reductase (in collaboration with C. Gomez-Moreno, Universidad de Zaragoza, and A. Aliverti, Universita de Milano), and mixed single- and two-electron reduction reactions by using mammalian mitochondrial complex I (in collaboration with A.D. Vinogradov, Moscow University), apoptosis inducting factor (in collaboration with I.F. Sevrioukova, California University, Irvine), lipoamide dehydrogenase, plant and bacterial thioredoxin reductases (in collaboration with J.-P. Jacquot and N. Rouhier, Universite de Nancy), and bacterial flavohemoglobin (in collaboration with L. Baciou and F. Lederer, Universite de Paris Sud). The single-electron reduction of quinones and nitroaromatic compounds by aforementioned enzymes is described by Marcus' model, and the rates are weakly influenced by the structure and VdWvol of the compounds. In several cases, the redox states of the enzymes responsible for the rate-limiting stage have been identified. Mixed single- and two-electron reduction is characterized by e-,H+,e- mechanism determined by the destabilization of neutral flavin semiquinone. Two-electron reduction by mammalian DT-diaphorase or bacterial nitroreductases decreases the cytotoxicity of simple quinone compounds, but increases the cytotoxicity of aziridinyl-substituted quinones and nitroaromatic compounds due to formation of DNA-alkylating products (Fig. 2). Fig. 2. Two-electron reduction of aziridinyl-substituted quinones with subsequent alkylation of DNA. It has been examined the reduction of quinones and nitroaromatic compounds mediated by DT-diaphorase, E. cloacae nitroreductase B (in collaboration with R. Koder, Kentucky University), PETN reductase (in collaboration with N.S. Scrutton, Manchester University), and E. coli nitroreductase A (in collaboration with D.F. Ackerley, Welington University). These reactions have been found to be characterized by a strong substrate structure specificity because of significant conformational changes of the enzyme active sites and by negative ∆S≠. Depending on the stability of anionic flavin semiquinone radical, these reactions proceed through single- (H-) or three-step (e-,H+,e-) hydride transfer. Mammalian cell culture cytotoxicity of quinones and nitroaromatic compounds. Applying several transformed and primary mammalian cell cultures (Center of Innovative Medicine), the cytotoxic action of quinones and nitroaromatics has been found to be mainly determined by the oxidative stress, and that the cytotoxicity of compounds increases with an increase in their single-electron reduction potential, with ∆log cL50/∆E17 of -8 – -10 V-1. Significantly increased cytotoxicity of aziridinyl-substituted quinones is attributed to their activation by DT-diaphorase. Aziridinyl-benzoquinone resistant cell sub-lines possess 10-fold decreased activity with DT-diaphorase and glutathione-S-transferase, whereas the activity of prooxidant and antioxidant enzymes varies in the limits of ±50%. Quinones and nitroaromatic compounds as inhibitors and subversive substrates of antioxidant flavoenzymes. Quinones and nitroaromatic compounds inhibit the antioxidant mammalian and parasite flavoenzymes glutathione reductase (GR) and trypanothione reductase (TR), and mammalian thioredoxin reductase (TrxR), thus inhibiting the regeneration of –SH groups in the cell. In parallel, they may be reduced by the aforementioned enzymes in mixed single- and two-electron way, thus subverting their antioxidant functions. The above mechanisms may be employed in the design of new antiparasitic and anticancer agents. The interaction of the above compounds has been examined with erythrocyte and P. falciparum GR (in collaboration with E. Davioud-Charvet, Universite de Strasbourg), T. congolense TR (in collaboration with J. Blanchard, Albert Einstein College of Medicine, NY), and mammalian TrxR (in collaboration with E. Arner, Karolinska Institutet). A number of efficient inhibitors of the above enzymes have been discovered. It has been established that apart from the reduced flavin, the above compounds may be reduced by the catalytic SeH-SH-moiety of TrxR. In collaboration with P. Grellier (MNHN, Paris), the relation between the efficiency of inhibition of P. falciparum GR by quinones and nitroaromatic compounds and their in vitro antiplasmodial activity has been established. Prooxidant cytotoxicity of polyphenols. The antioxidant activity of polyphenols (flavonoids, polihydroxybenzenes, etc.) relies on neutralization of ROS. Therefore they are considered as useful food components; their antitumour and antiparasitic activity have been examined. However, polyphenols possess prooxidant cytotoxicity, because during their (auto)oxidation, H2O2 and quinone/quinomethide oxidation products are formed which alkylate –SH groups in the cell. The cytotoxicity of polyphenols in several cell lines increases with a decrease in their single-electron oxidation potential (∆log cL50/∆E27 = 1 – 2 V-1 ), and with an increase in their lipophilicity. Hydroxylation and oxidative demethylation of polyphenols by cytochromes P-450 increases their cytotoxicity, whereas the methylation by catechol-O-methyltransferase decreases it. During the collaboration with P. Venskutonis (Kaunas Technological University), prooxidant cytotoxicity of a number of plant and herb polyphenolic extracts has been characterized. Key grants 2012-2017 National Research Projects funded by Research Council of Lithuania International Research Projects Key publications 2012-2017 Head dr. Regina Jančienė The Laboratory of Bioorganic Compounds Chemistry is a non-academic unit of the VU LSC Institute of Biochemistry, which carries out activities at the Section of Experimental Production located in Mokslininku Street, Vilnius. Besides research laboratories, the Section of Experimental Production has facilities and equipment for large volume organic synthesis and a separate unit adapted for high-pressure reactions. Research interests of Laboratory of Bioorganic Compounds Chemistry are the synthesis of amino acids and their derivatives, the search of synthesis pathways and the development of technologies for macrocyclic and linear polyethers and investigation of the synthesis, structural and other properties of various heterocycles. Since 2014 the main activities of Laboratory focused on the contractual projects. These studies are carried out in cooperation with Lithuanian and foreign business entities who are interested in introducing the results of research into practice. Our partners are Ramidus AB (Sweden), Synthon Chemicals GmbH (Germany), Polypure AS (Norway), Bapeks Ltd. (Latvia), Thermofisher Scientific Baltics UAB (Lithuania), UAB Elymus, (Lithuania), UAB Biotecha (Lithuania), UAB Ekorama (Lithuania), UAB Vilniaus Ventas Semiconductors (Lithuania). Current aim of our laboratory is closing the gap from laboratory to market via pilot-scale development. This activity enables to demonstrate the commercial potential of the new technology. The applied scientific research can be conducted both in laboratory and reactor scale. Our equipment includes different volume glass (20-100 L), glass-lined (10-1600 L) and stainless steel reactors (10-600 L), as well as autoclaves for catalytic hydrogenation (0.2-10 L) and different kinds of auxiliary equipment. We offer services to fellow scientists and business representatives in the field of organic synthesis: Our product portfolio contains over 200 compounds of various classes: O,N ir S-heterocyclic compounds thiols, thioethers and thioamides stereoisomeric disubstituted cyclohexane derivativesi aromatic carboxylic acids aminoacid derivatives mono- and disubstituted cyclic polyethers aminonaphthalensulfoamides monodisperse derivatives of polyethylene glycols enzyme cofactors These high quality fine chemicals for scientific and commercial purposes are produced from grams to hundreds of kilograms, depending on the compounds structure and requirement of the customers. Head dr. Mindaugas Valius Research interests ProjectsDepartment of Bioanalysis
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email: Third direction - the same bio-electro-catalytic system was applied in bioreactors for the selective conversion of substrates into useful products. Conversion of N-hydroxy- compounds, alcohols and other substrates catalysed by oxidoreductases (laccases, peroxidases and quinoprotein dehydrogenases) was investigated. These systems were extended into multi-step synthesis of natural products & analogues involving sequences of enzymes conversion chains.
Department participated in the international sheering of the food quality control knowledge. Food safety and Food safety assessment training courses were translated into Lithuanian language and distributed among food producers. Department participated in the introduction of ES Food safety legislation into food industry system in Turkey.
Department of Bioelectrochemistry and Biospectroscopy
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Department of Biological Models
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Department of Molecular Cell Biology
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Department of Molecular Microbiology and Biotechnology
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Department of Xenobiotics Biochemistry
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Laboratory of Bioorganic Compounds Chemistry
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Proteomics Centre
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