Institute of Biochemistry

Sukurta: 15 September 2013

bchi12 Mokslininkų, LT-08662 Vilnius
Tel. 272 9144, fax 272 9196
E-mail:
www http://www.bchi.vu.lt

Director - Prof. Habil. Dr. Valdas Laurinavicius

STAFF

58 research fellows (49 holding research degree), 18 doctoral students

RESEARCH AREAS

Signalling Pathways and Epigenetic Regulation in Cancer and Stem Cells
Investigation of the Structure and Function of Biocatalyzers
Study of the Structure and Function of Self-assembled Lipid Systems and Membrane Proteins

DOCTORAL DISSERTATIONS MAINTAINED IN 2013

M. Jankunec. Investigation of properties of lipid liquid crystalline drug carriers and their interactions with model cell membranes.
N. Krestnikova. Investigation of differentiated muscle-derived stem cell death and survival signalling mechanisms.
S. Kutanovas. Investigation of tetramethylpyrazine degradation in Rhodococcus sp. TMP1 bacteria.
E. Voitechovic. Oxidoreductases in bioelectrochemical systems: investigation and application.
Z. Strazdaite-Zieliene. Investigation of the impact of endoribonucleases on bacteriophage T4 early transcripts.

DEPARTMENT OF BIOANALYSIS

12 Mokslininkų, LT-08662
Tel. 272 9068, fax 272 9196
E-mail:

Head – Prof. Habil. Dr. Valdas Stanislovas Laurinavicius

STAFF

Chief research fellows, professors: Habil. Dr. V. Laurinavicius (part-time), Habil. Dr. V. Razumas (part-time), Habil. Dr. J. Kulys (part-time).
Senior research fellows : Dr. J. Razumiene, Dr. R. Simkus, Dr. R. Vidziunaite.
Research asociate: Dr. B. Kurtinaitiene, Dr. L. Tetianec.
Junior research fellows: I. Bratkovskaja, Dr. M. Dagys, V. Gureviciene.
Doctoral students: A. Chaleckaja, A. Laurynenas, I Sakinyte.
Technical staff: A. Jonuska, N. Baluckiene, L. Giniotiene, J. Matulevic, J. Puzas.

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.

RESEARCH PROJECTS CARRIED OUT IN 2013

Project Supported by University Budget

Biocatalitic Systems for Analysis and Synthesis . Prof. Habil. Dr. V. S. Laurinavičius. 2011–2016.

Investigation of the catalytic activity and specificity of the oxidoreductases and their application in bioanalytical systems and bioreactors.

Investigation of the bioelectrocatalytical parameters of fungal laccases.

Develop mathematical model of the pH dependence of oxidation of ascorbic acid on the monolayers of the self- assembled structures based on ferrocene derivatives.

Novel methods for efficient fungal laccase adsorption on nanosurfaces in order to achieve direct electron transfer bioelectrocatalysis were investigated.

High current density direct electron transfer based biocathodes were created by using fungal laccases and gold nanosurfaces. New chemically modified carbon black-based matrixes were synthesized for the efficient wiring of oxidases and dehydrogenases. Mathematical modelling of bioelectrocatalytical systems were performed and mathematical models of the systems with unstable signal were derived.

Main publications:

Meškauskas, T., Ivanauskas, F., Laurinavicius, V., 2013. Degradation of substrate and/or product: mathematical modeling of biosensor action. J. of Mathematical Chemistry, vol. 51, No. 6, 2491–2502.

Meškauskas, T., Ivanauskas, F., Laurinavicius, V., 2013. Numerical Modeling of Multilayer Biosensor with Degrading Substrate and Product. 8-th EUROSIM Congress on Modelling and Simulation Proceedings, 24–29.

Šimkus, R., Baronas, R., Ledas, Ž., 2013. A multi-cellular network of metabolically active E. coli as a weak gel of living Janus particles. Soft Matter, vol. 9, 4489–4500.

National Research Projects

Research Council of Lithuania. Bee products enriched with plant components, the composition and properties (SVE-01/2012). Dr. B. Kurtinaitiene. 2012–2015.

Evaluated enzyme activity and anti-oxidant activity of a number of bee products. Optimized method of the extraction of the proteins from the pollen for the certification of honey nature.

Main publications:

Čeksterytė, V., Kurtinaitienė, B., Balžekas, J., 2013. Pollen diversity in honey collected from Lithuania’s protected landscape areas. Proceedings of the Estonian Academy of Sciences, 62, 4, 277–282.

Projects supported by the European Social Fund

Project supported by the European Social Fund under National Integrated Programme Biotechnology & Biopharmacy, grant VP1-3.1-SMM- 08-K01-005/ KS-560000-1757. 2012–2015. Action 1.1.4. Creation of biocatalysts and biocatalytic processes for bioconversion of carbohydrates. Head of Action Dr. J. Razumiene.

Aiming to create new bioconversion and controlling systems using immobilized biocatalysts – enzymes organic and inorganic supports promising for immobilization have been synthesized and investigated. The screening of new oxidoreductases, lipases, izomerazes and aldolases possessing beneficial features has been performed. The investigations of biocatalysts in terms to stabilize those using newly synthesized supports are carrying on.

Main publications:

Laurinavicius, V., Razumiene, J., Gureviciene, V., 2013. Bioelectrochemical conversion of urea on Carbon Black Electrode and Application. IEEE Sensors Journal, Vol. 13, No. 6, 2208–2213.

Razumiene, J., Sakinyte, I., Kochane, T., Maciulyte, S., Straksys, A., Budriene, S., Barkauskas, J., 2013. Carbon Electrode based Urea Sensor - Modification of Graphite and New Polymeric Carriers for Enzyme Immobilization. BIODEVICES 2013. Proceedings of the International Conference on Biomedical Electronics and Devices, Barcelona, Spain, 11–14 February, p. 328. SciTePress 2013, p. 197–201.

International Research Projects

7 FW Leonardo da Vici Program. Food Industry - Food Legislation, Impact Analysis, Training and Cooperation Network in Europe -E-Learning, 2012-1-TR1-LEO05-35116, 2012–2014.

Food safety training courses were translated into Lithuanian language and distributed among food producers. Seminar about modern methods in bioanalysis was organized at the National Food and Veterinary Risk Assessment institute.

MAIN R&D&I (RESEARCH, DEVELOPMENT AND INNOVATION) PARTNERS

Gaziantep University (Turkey)

OTHER SCIENTIFIC ACTIVITIES

Prof. Habil. Dr. V. Laurinavičius –

  • member of Lithuanian Academy of Sciences;
  • member of the Council of the Vilnius University International Business School;
  • member of the Editorial Boards of: Nonlinear Analysis: Modelling and Control, Chemija and Journal of Theoretical Chemistry.
  • European Commission Specific Program Ideas, expert from Lithuania.
  • member of the Board of the Lithuania Biotechnology Association.

Prof. Habil. Dr. V. Razumas –

  • President of the Lithuanian Academy of Sciences;
  • Chairman of the Lithuanian Science Awards Commission;
  • member of the Board of the Research Council of Lithuania.

Prof. Habil. Dr. J. Kulys –

  • member of the Lithuanian Academy of Sciences;
  • member of Europe Biotechnology Federation;
  • member of Europe Applied Biocatalysis Association;
  • member of Lithuanian Biotechnology Association;
  • member of Lithuanian Biochemistry Association;
  • editor of the Biosensors & Bioelectronics;
  • member of the Editorial Boards of: The Open Nanoscience Journal, The Open Enzyme Inhibition Journal, The Open Biotechnology Journal, Biologija and Nonlinear Analysis, Modelling and Control.

DEPARTMENT OF BIOELECTROCHEMISTRY AND BIOSPECTROSCOPY

12 Mokslininkų, LT-08662
Tel. 272 9186, fax 272 9196
E-mail: ,

Head – Dr. Gintaras Valinčius

STAFF

Chief research fellows: Dr. G. Valinčius, Habil. Dr. G. Niaura.
Junior research fellows : Dr. A. Bulavas, Dr. R. Budvytytė, Dr. M. Jankunec.
Doctoral students : T. Ragaliauskas, M. Talaikis, N. Dzingelevičius, J. Latynis, M. Mickevičius.

RESEARCH FIELDS

Spectroelectrochemistry of proteins and biologically relevant redox species
Self-organizing lipid systems, including phospholipid bilayer membranes
Interaction with proteins
Development of measurement techniques: electrochemical impedance spectroscopy, modulated surface stress, sum-frequency generation, and surface enhanced Raman spectroscopy

RESEARCH PROJECTS CARRIED OUT IN 2013

Projects Supported by University Budget

Spectroelectrochemical Studies of Biological Systems and their Models. Dr. G. Valincius. 2011–2015.

Electrochemical study of peptides, proteins, and redox active compounds entrapped into the tethered model cell membranes as well as membranes designed from the compositions of natural lipids.

Vibrational spectroscopic study of membrane relevant self-assembled monolayers formed on silver and structurized metal surfaces prepared by laser ablation.

The applicability of artificial tethered bilayer membranes (tBLMs) as a bioanalytical platform for the detection of the activity of the cholesterol-dependent cytolysin vaginolysin was demonstrated. The monolayers of new unsaturated lipidic molecule (HC18) for formation of tBLMs were studied by spectroscopic and electrochemical methods. Our data indicate that HC18 results in tBLMs with improved physical properties for the incorporation of integral membrane proteins.

Main publications:

Budvytyte, R., Pleckaityte, M., Zvirbliene, A., Vanderah, D. J., Valincius, G., 2013. Reconstitution of cholesterol-dependent vaginolysin into tethered phospholipid bilayers: implications for bioanalysis. PLOS ONE. DOI: 10.1371/journal.pone.0082536.

Kocherbitov, V., J. Latynis, A. Misiūnas, J. Barauskas, G. Niaura, 2013. Hydration of lysozyme studied by Raman spectroscopy. Journal of Physical Chemistry B, 117, 4981-4992.

Budvytyte, R., M. Mickevicius, M., Vanderah, D. J. Heinrich, F., Valincius, G.,2013. Modification of Tethered Bilayers by Phospholipid Exchange with Vesicles. Langmuir. 29, (13), 4320–4327.

Projects, Programmes, Issues Supported by Research Council of Lithuania

Research Council of Lithuania. Molecular Mechanisms of Alzheimer’s Pathogenesis. – Joint project with Lithuanian University of Health Sciences headed by Dr. R. Morkuniene (LIG-04/2012). 2012–2014.

Project aims at establishing molecular scale factors that trigger Alzheimer‘s pathogenesis. In particular amyloid beta oligomers, their physical and chemical properties are studied in parallel to their biological activity.

Main publications:

Morkuniene, R., Zvirbliene, A., Dalgediene, I., Cizas, P., Jankeviciute, S., Baliutyte, G., Jokubka, R., Jankunec, M., Valincius, G., Borutaite, V., 2013. Antibodies bound to Aβ oligomers potentiate the neurotoxicity of Aβ by activating microglia. Journal of Neurochemistry, 126, 604– 615.

Dalgediene, I., Lasickiene, R., Budvytyte, R., Valincius, G., Morkuniene, R., Borutaite, V., Zvirbliene, A., 2013. Immunogenic properties of amyloid beta oligomers. Journal of Biomedical Science, 20: doi:10.1186/1423-0127-20-10.

Budvytyte, R., Valincius, G., Niaura, G., Voiciuk, V., Mickevicius, M., Chapman, H., Goh, H.-Z., Shekhar, P., Heinrich, F., Shenoy, S., Lösche, M., Vanderah, D. J., 2013. Structure and Properties of Tethered Bilayer Lipid Membranes with Unsaturated Anchor Molecules. Langmuir, 29 (27), 8645 –8656.

Project supported by the European Social Fund and Ministry of Education and Science of the Republic of Lithuania

Miniaturized Phospholipid Biosensors (VP1-3.1-ŠMM-10-V-02-024) Dr. G. Valincius 2013–2015.

Project aims at development of new generation of miniaturized devices for the detection of toxic proteins such as heamolysin, streptolysin, pneumolysin and others. We utilize the technology based on tethered bilayer membranes. Electrochemical impedance response is used to detect membrane damaging events.

MAIN R&D&I (RESEARCH, DEVELOPMENT AND INNOVATION) PARTNERS

Institute of Biomedical Research of LSMU, Kaunas (Lithuania)
Altechna R&D Co., Vilnius (Lithuania)
Carnegie Melon University, Pittsburgh, PA (USA)
National Institute of Standards and Technology, Gaithersburg, MD (USA)
University of Maryland Institute of Biotechnology, Rockville, MD (USA)
University of Cracow, Cracow (Poland)

OTHER SCIENTIFIC ACTIVITIES

Dr. G. Valinčius –

  • Lithuanian representative in European Strategy Forum for Research Infrastructures (ESFRI);
  • Lithuanian representative in the Program Committee of Infrastructures of the specific program Capacities of FP7.

Habil. Dr. G. Niaura –

  • member of the Lithuanian Academy of Sciences.

Dr. R. Budvytytė –

  • member of the American Biophysical Society.

DEPARTMENT OF BIOORGANIC COMPOUNDS CHEMISTRY

12A Mokslininkų, LT-08662 Vilnius
Tel.: 272 9058, fax: 272 9196
E-mail:

Head – Dr. Regina Jančienė

STAFF

Senior research fellows: Dr. A. Palaima, Dr. R. Jančienė.
Research fellows: Dr. A. Klimavičius, Dr. Z. Staniulytė, Dr. L. Kosychova.
Junior research fellow: Dr. R. Sirutkaitis.

RESEARCH INTERESTS

Synthesis of heterocyclic, amino acid and polyether derivatives

RESEARCH PROJECTS CARRIED OUT IN 2013

Projects Supported by University Budget

Investigation of the Synthesis and Structure, Study of the Practical Usage of Modulators and Catalysts of Biological Processes. Dr. R. Jančienė. 2011-2013.

Investigation of the synthesis of stereoisomeric aminocyclohexaneacetic acid derivatives, Study of the usage of various protecting groups for the synthesis of polyethylene glycol derivatives, Synthesis of new tricyclic fused 1,5-benzodiazepine derivatives with high heteroatom density.

Stereospecific conditions of catalytic hydrogenation of phenylacetic acid derivatives were investigated and 4-aminocyclohexaneacetic acid saturated by 80% with cis- or trans-isomer was obtained. Taking advantage of different solubility of isomers or their hydrochlorides, purification method was proposed.

Nonaethylene glycol mesylation reaction was investigated and factors essential for the purity of disubstituted product were established. Optimal conditions enabling to synthesize bigger quantities of pure oligomere were chosen.

The derivatives of a new heterosystem, [1,3,5,2]oxadiazaphospholo[3,4-a][1,5]benzodiazepin-1-amine-1-oxides, were synthesized via interaction of 5-substituted 1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one oximes with dimethylamidophosphoric dichloride.

Main publications:

Janciene, R., Vektariene, A., Mikulskiene, G., Javorskis, T., Vektaris, G., Klimavicius, A., 2013. A combined experimental and theoretical study of the synthesis of quinazolino[3,2-a][1,5]benzodiazepin-13-ones. ARKIVOC: Archive for Organic Chemistry, part. 4, 57–75.

National Research Projects

MITA Synthesis of pantetine-4‘,4‘‘-diphosphate (National program to support R&D contracts). Nr. 31V-100/LSS-14100-2266 Dr. A. Palaima. 2013.

Methods of synthesis of pantethine-4',4''-diphosphate were developed, reaction conditions of separate steps were optimizated, developed technology was applicated for the preparative synthesis and the experimental batches were prepared.

MITA Research in development of new methods for mesylations of diols (National program to support R&D contracts). Nr. 31V-100/LSS-14100-2266. Dr. A. Palaima. 2013.

Method of mesylation of nonaethylene glycol was developed and experimental batches suitable for the further syntheses were prepared.

Contractual Research:

Synthesis of pantetine-4‘,4‘‘-diphosphate. Contract with CJSC Fermentas/ CKSC Thermo Fisher Scientific Baltics. Dr. A. Palaima.

Investigation of synthesis methods for various organic compounds. Contract with Synthon Chemicals GmbH (Germany), Dr. A. Palaima.

Investigation of synthesis of isomerically pure cis/trans cyclohexane derivatives. Contract with Bapeks SIA (Latvia). Dr. A. Palaima.

Research in development of new methods for mesylations of diols . Contract with Ramidus AB (Sweden), Dr. A. Palaima.

Investigation of Regeneration Conditions of Butylacetate and Negative Developer and Manufacturing of their Experimental Batches. Contract with CJSC Vilniaus Ventos puslaidininkiai. Dr. A. Klimavičius.

MAIN R&D&I (RESEARCH, DEVELOPMENT AND INNOVATION) PARTNERS :.

CJSC Thermo Fisher Scientific Baltics (Lithuania)
Ramidus AB (Sweden)
Polypure AS (Norway)
Synthon Chemicals GmbH & Co.KG (Germany)
Centre of Physical Sciences and Technology (Lithuania)

DEPARTMENT OF MOLECULAR CELL BIOLOGY

12 Mokslininku, LT-08662 Vilnius
Tel.: 272 9327, fax: 272 9196
E-mail:

Head – Prof. Rūta Navakauskienė

STAFF

Senior research fellow: Dr. A. Kalvelytė.
Research fellows: Dr. G. Treigytė, Dr. J. Savickienė, Dr. V. V. Borutinskaitė, Dr. A. Imbrasaitė.
Junior research fellow: A. Stulpinas.
Senior specialist: Dr. N. Krestnikova.
Doctoral students: S. Baronaitė, G. Vištartaitė.

RESEARCH INTERESTS

Studies of molecular mechanisms in normal and cancer cells to determine new possibilities of leukemia differentiation therapy
Identification of proteins that might be involved in signaling events that mediate cancer cell differentiation
Studies of apoptosis signaling in cancer and adult stem cell models in vitro

RESEARCH PROJECTS CARRIED OUT IN 2013

Projects Supported by University Budget

Study of the Mechanisms of Eukaryotic Cell Proliferation, Differentiation and Apoptosis . Joint project with Center of Proteomics and Department of Molecular models. Prof. Dr. R. Navakauskiene. 2011–2015.

To Examine the Effects of Epigenetic Modifiers EGCG and Bml-210 on the Expression of p16 in Human Cancer and Stem Cells. Prof. Dr. R. Navakauskiene.

Epigenetic changes such as histone acetylation and DNA methylation play an important role in human cancer cells. In our study we have used epigenetic modifiers EGCG and Bml-210. We focused on epigenetic status of cell cycle regulating biomolecule - p16. We showed that the methylation level in promoter region of the p16 gene is considerably higher in leukemic KG1 cells, representing blocked differentiation at an early stage of hematopoietic development and lower in human hematopoietic progenitor CD34+ cells. The effect of EGCG and Bml-210 at the concentrations used was negligible on the muscle derived stem cells.

Main publications:

Kalvelyte, A, Krestnikova, N., Stulpinas, A., Bukelskiene, V., Bironaite, D., Baltriukiene, D., Imbrasaite, A., 2013. Long-term muscle-derived cell culture: multipotency and susceptibility to cell death stimuli. Cell Biology International, 37, 292–304.

National Research Projects

Research Council of Lithuania. Multiplexed Molecular Biomarker Study for Leukemia (No. LIG-06/2012) Prof. R. Navakauskienė 2012–2014.

Changes in the epigenetic landscape play a crucial role in leukemia pathogenesis. In this study we investigated the effect of histone methyltransferase (HMT) inhibitors BIX, 3-DZNeplanocin A and histone deacetylases (HDAC) inhibitor Belinostat in combination with retinoic acid on human acute promyelocytic leukemia NB4 cells granulocytic differentiation.

Research Council of Lithuania. Cytological, Molecular and Epigenetic Studies of Amniotic Fluid (No. MIP-033/2013). Dr. G. Treigytė. 2013 –2015.

Project goal - to study amniotic fluid cytological, molecular and epigenetic differences between normal and pathologic pregnancy. In this study, the proteome of human amniotic fluid of normal and pathologic pregnancy are profiled and analyzed.

Research Council of Lithuania. National Science program project Bee Products Enriched with Plant Components, the Composition and Properties (No. SVE-01/2012). 2012–2015.

Honey samples were selected from various Lithuanian regions. Protein extraction from pollen conditions was optimized. A protein precipitation with acetone solution was chosen and protein extractions in 1D and 2D systems were performed. That will allow further pollen protein qualitative fractionation and honey species identification.

International Science Programs and Projects

COST Action CM1106: Chemical Approaches to Targeting Drug Resistance in Cancer Stem Cells (StemChem). Prof. R. Navakauskienė 2011 –2015.

This COST Action aims at uniting researchers with expertise in rational drug design and the medicinal chemistry with biomedical investigators dedicated to the understanding the mechanisms governing drug resistance in cancer stem cells. The Action aim is to develop new, effective methods for identifying novel compounds that target drug-resistant cancer stem cells.

Projects supported by the European Social Fund

Participation in the project supported by the European Social Fund under National Integrated Programme Biotechnology & Biopharmacy, grant VP1-3.1-SMM- 08-K01-005. 2012–2015. Action 1.1.3. Molecular processes in eukaryotic cells: the technological and medical aspects (Head of Action Prof. Dr. R. Navakauskiene).

The aim of the action is to develop new diagnostic and therapeutic tools for the management of molecular processes and the mechanisms in stem and cancer cells.

Participation in Global grant under the European Union Structural Funds programme Molecular Mechanisms of Toxicity and Antitumour Activity of Quinones and Polyphenols: Qsars in the Enzymatic Redox Reactions and Cytotoxicity, Signal Transduction, and Proteomics (VP1-3.1-ŠMM-07-K-01-103). Habil. Dr. N. Čenas. 2011–2015.

Cell death-signalling mechanisms of bioreductively-activated aziridinyl-substituted RH-1quinone in DT- diaphorase bearing lung cancer A549 line cells are studied.

MAIN R&D&I (RESEARCH, DEVELOPMENT AND INNOVATION) PARTNERS

Linköping University (Sweden)

DEPARTMENT OF XENOBIOTICS BIOCHEMISTRYa

and

DEPARTMENT OF SCIENTIFIC INFORMATIONb

12 Mokslininkų, LT-08662 Vilnius
Tel. 272 9042a, 272 9195b, fax 272 9196
E-mails: ,

Heads – Habil. Dr. Narimantas Čėnasa, Dr. Kastis Krikštopaitisb

STAFF

Chief research fellow: Habil. Dr. N. Čėnas.
Senior research fellows: Dr. Ž. Anusevičius, Dr. K. Krikštopaitis, Dr. J. Šarlauskas.
Research fellows: Dr. A. Marozienė, Dr. G. Mikulskienė, Dr. V. Miliukienė, Dr. L. Misevičienė, Dr. H. Nivinskas.
Doctoral students: R. Jarašienė, E. Polmickaitė.

RESEARCH INTERESTS

Molecular mechanisms of enzymatic activation, detoxification, biodegradation, and cytotoxicity of redox active xenobiotics

RESEARCH PROJECTS CARRIED OUT IN 2013

Projects Supported by University Budget

Synthesis, Studies of Physicochemical Properties, Enzymatic Reactions and Cytotoxicity of Quinones and Nitroheterocyclic Compounds Possessing Antiparasitic Activity. Habil. Dr. N. Čėnas. 2011–2016.

We characterized the electrochemistry of 9 derivatives of antitumour agent tirapazamine (TPZ). The reactivity of TPZs towards the single-electron transferring flavoenzymes which is related to their oxidative stress-type cytotoxicity, correlated with their electron accepting potency, which was not characteristic for the two-electron transferring DT-diaphorase. The mammalian cell cytotoxicity of TPZs is weakly influenced by their electron accepting potency. The toxicity of TPZ was partly prevented by the antioxidants, and the inhibitor of NQO1. These data point to a mixed character of cytotoxicity of TPZs.

Main publications:

Šarlauskas, J ., Nemeikaitė-Čėnienė, A., Misevičienė, L., Krikštopaitis, K., Anusevičius, Ž., Čėnas, N., 2013. Redox properties and prooxidant cytotoxicity of a neuroleptic agent 6,7-dinitrodihydroquinoxaline-2,3-dione (DNQX). Acta Biochimica Polonica, 60, 227– 231.

Anusevicius, K., Vaickelioniene, R., Mickevicius, V., Mikulskiene, G., 2013. Synthesis of bis azole, diazole, and triazole derivatives from n-(4-chloro/iodophenyl)-n-carboxyethyl-beta-alanine dihydrazides. Journal of Heterocyclic Chemistry, 50, 309–314.

Vaickelionienė, R., Mickevičius, V., Mikulskienė, G., 2013. Synthesis and characterization of 4-substituted 1-(4-halogenophenyl)pyrrolidin-2-ones with azole and azine moieties. Heterocycles, 87, 1059–1074.

National Research Projects

Research Council of Lithuania. Quinones and Nitroaromatic Compounds as the Subversive Substrates for Flavohemoglobin: Mechanisms and Biomedical Implications (bilateral French-Lithuanian program Gilibert, No. TAP LZ07/2013). N. Čėnas. 2013–2014.

We purified the recombinant flavohemoglobin (flavoHb) (Vilnius and Orsay teams at Orsay), studied its steady-state quinone reductase reactions (Vilnius team in Vilnius), and its presteady-state reduction under the aerobiosis (Vilnius and Orsay teams in Vilnius). Besides, a member of Vilnius team studied the techniques of the presteady-state reduction under anaerobiosis at Orsay, as well as the analysis of flavin content in the enzymes under guanidine chloride denaturing conditions. .

Research Council of Lithuania. The Characterization of the Interprotein Interaction and the Modulators of the Redox Equivalent Transfer in Steroid Hydroxylation Systems (bilateral Belarus-Lithuanian program, No. TAP LB02/2013). Ž. Anusevičius. 2013–2014.

Recombinant flavoenzymes participating in steroid hydroxylation were purified in Minsk (Minsk and Vilnius teams). Their reactions with quinoidal and nitroaromatic compounds as the possible modulators of the electron transfer were studied in Vilnius by Vilnius team. The Minsk team in Vilnius performed the stopped-flow studies of substrate and inhibitor binding to cytochromes P-450. A next stay of Vilnius team to Minsk involved the hplc/ms studies of the nitroreductase reaction products of flavoenzymes participating in steroid hydroxylation systems, and some model flavoenzymes.

Projects supported by the European Social Fund

Research Council of Lithuania. Molecular Mechanisms of the Toxicity and Antitumour Activity of Quinones and Polyphenols: Enzymatic Redox Reactions, Cytotoxicity, Signal Transduction and Proteomics (Global grant, Nr. VP1-3.1-ŠMM-07-K01-103), Habil. Dr. N. Čėnas. 2011–2015.

Several analogues of the antitumour agent BZQ were synthesized, their redox and cytotoxicity properties were studied We identified NO-synthase as a source for the oxidative stress-type cytotoxicity of quinones. We obtained two cell sublines resistant to the antitumour agent RH1 with the markedly decreased levels of DT-diaphorase. Their proteomic studies are underway. The studies of apoptosis induction by the prooxidant action of H2O2, duroquinone, RH1, and quercetin revealed some differences in the expression of kinases and phosphatases participating in the signal transduction.

Main publications:

Anusevičius, Ž., Nivinskas, H., Šarlauskas, J., Sari, M.-A., Boucher, J.-L., Čėnas, N., 2013. Single-electron reduction of quinone and nitroaromatic xenobiotics by recombinant rat neuronal nitric oxide synthase. Acta Biochimica Polonica, 60, 217–222.

MAIN R&D&I (RESEARCH, DEVELOPMENT AND INNOVATION) PARTNERS

Universite de Paris-Sud, Orsay (France)
Universite de Rene Descartes, Paris (France)
Universite Lorraine, Nancy (France)
The Manchester University (UK)
Institute of Bioorganic Chemistry of the NAS of Belarus, Minsk (Belarus)

DEPARTMENT OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY

12 Mokslininkų, LT-08662 Vilnius
Tel. 272 9149, 272 9146, , fax 272 9196
E-mail:

Head – Dr. Rolandas Meškys

STAFF

Chief research fellow: Dr. R. Meškys.
Senior research fellows: Dr. L. Truncaitė, Dr. I. Bachmatova, Dr. J. Urbonavičius.
Research fellows: Dr. A. Zajančkauskaitė, Dr. L. Kalinienė; Dr. L. Marcinkevičienė, Dr. R. Rutkienė, Dr. V. Časaitė Dr. D. Tauraitė.
Junior research fellows: Dr. R. Gasparavičiūtė, R. Meškienė, Dr. S. Povilionienė, Dr. R. Stanislauskienė, J. Stankevičiūtė.
Senior assistants: Dr. J. Kiuberis, S. Kutanovas.
Doctoral students: Ž. Strazdaitė-Žielienė, E. Šimoliūnas, J. Vaitekūnas, L. Adamonytė, A. Aučynaitė.

RESEARCH INTERESTS

Molecular biology and genetics of bacteria and bacteriophages

Genetic and biochemical diversity of microorganisms, enzyme biotechnology

RESEARCH PROJECTS CARRIED OUT IN 2013

Projects Supported by University Budget

Changes in Metabolism of Bacterial Nucleic Acids During the Infection of Virulent Bacteriophages Dr. L. Truncaitė. 2011–2015.

The use of RegB endoribonuclease for the degradation of plasmid-induced transcripts.

Expression of the sequence-specific RegB endoribonuclease of either phage T4 or RB49 have been induced from recombinant plasmids along with the transcripts carrying RegB targets. Transcriptional analysis showed that RegB can cleave specific targets carried by plasmid-induced transcripts. Degradation of such transcripts can be further stimulated by simultaneous induction of the cloned T4 polynucleotide kinase. The amounts of transcripts can be modulated by mutagenesis of RegB targets.

Main publications:

Šimoliūnas, E., Kalinienė, L., Truncaitė, L., Zajančkauskaitė, A., Staniulis, J., Kaupinis, A., Ger, M., Valius, M., Meškys, R., 2013. Klebsiella phage vB_KleM-RaK2 - a giant singleton virus of the family. Myoviridae. PLOS One, 8(4), e60717. doi:10.1371/journal.pone.0060717.

Strazdaitė-Žielienė, Ž., Zajančkauskaitė, A., Kalinienė, L., Meškys, R., Truncaitė, L., 2013. A mutation in the gene for polynucleotide kinase of bacteriophage T4 K10 affects mRNA processing. Archives of Virology. Doi: 10.1007/s00705-013-1800-x.

Investigation of Microbial Catabolic Pathways. Dr. R. Meškys.

Screening and identification of coumarins-degrading microorganisms.

Several coumarin-induced proteins were isolated and identified from Rhodococcus sp. strains K5 and TMP1. Rhodococcus sp. K5 produced coumarin-inducible 3-(2-hydroxyphenyl) propionic acid 3-monooxygenase and 2-hydroxy-6-ketonona-2,4-dienedioic acid hydrolase. Both enzymes are involved in degradation of 3-(2-hydroxyphenyl)propionic acid, which is the main intermediate of coumarin biodegradation. The genes, encoding coumarin degrading enzymes in Rhodococcus jostii TMP1 and K5, were identified.

Main publications:

Kutanovas, S., Rutkienė, R., Urbelis, G., Tauraitė, D., Stankevičiūtė, J., Meškys, R., 2013. Bioconversion of methylpyrazines and pyridines using novel pyrazines-degrading microorganisms. Chemija, 24, 67–73.

Karvelis, L., Gasparavičiūtė, R., Klimavičius, A., Jančienė, R., Stankevičiūtė, J., Meškys, R.. 2013. Pusillimonas sp. 5HP degrading 5-hydroxypicolinic acid. Biodegradation DOI 10.1007/s10532-013-9636-3.

Kutanovas, S., Stankeviciute, J., Urbelis, G., Tauraite, D., Rutkiene, R., Meskys, R., 2013. Identification and characterization of tetramethylpyrazine catabolic pathway in Rhodococcus jostii TMP1. Appl. Environ. Microbiol., 79, 3649–3657. doi:10.1128/AEM.00011-13.

RESEARCH PROJECTS CARRIED OUT IN 2013

Projects, Programmes, Issues Supported by Research Council of Lithuania

Research Council of Lithuania. Development of Methods for Screening and Expression of Baeyer-Villiger Monooxygenases. (MIP-042/2012). Dr. R. Meškys. 2012–2014.

During implementation of the OXYMORON project new and unique data on Baeyer-Villiger monooxygenases has been collected, new potential substrates for these enzymes have been prepared, new inducible promoters applicable for non-standard hosts have been identified and characterized. Novel Ochrobactrum strain converting 3-acetylindole into indigo dye has been screened. Ten novel Baeyer-Villiger monooxygenases have been identified and their encoding genes have been cloned by using substrates prepared during this study.

Main publications:

Marcinkeviciene, L., Vidziunaite, R., Tauraite, D., Rutkiene, R., Bachmatova, I., Morkunas, M., Razumiene, J., Casaite, V., Meskiene, R., Kulys, J., Meskys, R., 2013. Characterization of laccase from Coriolopsis byrsina GRB13 and application for synthesis of redox mediators. Chemija, 24, 48–58.

Research Council of Lithuania. tRNA Modification Pathways – Evidence of the Enzyme Evolution. (MIP-043/2012) Dr. J. Urbonavičius. 2012–2014.

The aim of the project is the biochemical investigation of the enzymes in pathways, leading to formation of the wyosine derivatives in tRNRPhe in Archaea. During the course of this project, following results have been obtained in 2013. The expression of previously cloned six Achaeal genes, possibly involved in the biosynthesis of the wyosine derivatives, was optimised in the E. coli host cells. All six recombinant proteins were purified to >95% purity using the Ni ion affinity chromatography. The enzymatic activity of four out of six purified proteins was demonstrated

Research Council of Lithuania. Adaptation of Invasive Species and their Impact on Aquatic Ecosystems of Different Complexity. (LEK-10/2012). Dr. R. Meškys. 2012–2015.

This project aims at investigating adaptation of invasive species and their impacts on aquatic ecosystems. For the first time the comparative investigation of symbionts and intestine microflora of these crayfish species has been undertaken to reveal their differences in microbial functional diversity. The specific for the spiny-cheek crayfish were symbionts from the mycoplasma group, while that for the noble crayfish were microorganisms from the separate (IV) group.

Contractual Research

Generation of Metagenomic Gene Libraries and Screening for Decarboxylases, Bayer Materialscience AG, Germany, Dr. R. Meškys.

Selection of Enzymes through Uracil Auxotrophic E. Coli Strains , Bayer Technology Services GmbH, Germany, Dr. R. Meškys.

MAIN R&D&I (RESEARCH, DEVELOPMENT AND INNOVATION) PARTNERS

Centre for Physical Sciences and Technology (Lithuania)
Nature Research Centre (Lithuania)
Bayer Technology Services GmbH (Germany)

PROTEOMICS CENTRE

12 Mokslininku., LT-08662 Vilnius
Tel. 272 9187; Fax 272 9196
E-mail:

Head – Dr. Mindaugas Valius

STAFF

Research fellows: Dr. M. Valius, Dr. A. Kaupinis.
Junior research fellows Dr. M. Ger.
Doctoral students: D. Kučiauskas, A. Androšiūnaitė.

RESEARCH INTERESTS

High throughput proteomics analysis of cell signalling
Elucidation of artificial microstructures and nano particles on cell functioning
Studies of RAS-dependent signalling pathways in various cell culture models

RESEARCH PROJECTS CARRIED OUT IN 2013

Projects Supported by University Budget

Study of the Mechanisms of Eukaryotic Cell Proliferation, Differentiation and Apoptosis (Joint project with Department of Molecular Cell Biology and Department of Molecular Models; headed by prof. R. Navakauskienė). 2011–2015.

Investigation of Nck1 interactome by mass spectrometry. Dr. M. Valius.

Recently we have demonstrated that adaptor protein NCK1 directly interacts and activates the RASA1 protein, which is a key regulator of the Ras-dependent signaling pathway. Now we asked what other proteins may interact with NCK1. We performed high throughput proteomic analysis of NCK1 interactome and identified over 20 proteins that form complex with NCK1. Bioinformatics analysis of these proteins revealed that NCK1 might be involved in endocytosis processes.

Main publications:

Damalakiene, L., Karabanovas, V., Bagdonas, S., Valius, M., Rotomskis, R., 2013. Intracellular distribution of nontargeted quantum dots after natural uptake and microinjection. Int J Nanomedicine, 8, 555–68.

Simoliūnas, E., Kaliniene, L., Truncaitė, L., Zajančkauskaitė, A., Staniulis, J., Kaupinis, A., Ger, M., Valius, M, Meškys, R., 2013. Klebsiella phage vB_KleM-RaK2 - a giant singleton virus of the family Myoviridae. PLoS One, Apr 9, 8(4):e60717.

National Research Projects

Agency for Science, Innovation and Technology. Creation of Biologically Active Regular Three-Dimensional Structures for Tissue Molecular Bioengineering (No 31V-39/2012). Dr. M. Valius. 2012–2013.

We have developed a new method to create and decorate 3D micro-structures with biologically active molecules (proteins). The method is based on laser-guided photo-polymerization and photo-chemical activation of 3D surfaces.

Research Council of Lithuania. Molecular Mechanisms of the Toxicity and Antitumour Activity of Quinones and Polyphenols: Enzymatic Redox Reactions, Cytotoxicity, Signal Transduction and Proteomics (Global grant, Nr. VP1-3.1-ŠMM-07-K01-103). N. Čėnas. 2011–2015.

We have performed high throughput proteomics analysis of a few blood tumour cell lines sensitive and resistant to the experimental cancer drug RH1. We have identified and quantitated over 7 000 proteins; over 500 protein quantity changed 1.5 times and more. These proteins were analyzed by various bioinformatics tools and clustered into functional groups that represent biological processes. A few new biological processes were found to be attributed to the drug resistance.

Projects supported by the European Social Fund

Participation in the project supported by the European Social Fund under National Integrated Programme Biotechnology & Biopharmacy, grant VP1-3.1-SMM- 08-K01-005. Action 1.1.3 - Molecular processes in eukaryotic cells: the technological and medical aspects (Head of Action Prof. Dr. R. Navakauskiene). 2012–2015.

We have applied quantitative label-free proteomics analysis to find differences in protein expression level of ionization-sensitive and ionization-resistant human breast cancer tumour cell lines and found over 1000 proteins that expression were changed significantly. Bioinformatics analyses of these proteins are underway.

Participation in Global grant under the European Union Structural Funds programme - Molecular Mechanisms of Toxicity and Antitumour Activity of Quinones and Polyphenols: Qsars in the Enzymatic Redox Reactions and Cytotoxicity, Signal Transduction, and Proteomics (VP1-3.1-ŠMM-07-K-01-103). Habil. Dr. N. Čenas. 2011–2015.

We have performed high throughput proteomics analysis of a few blood tumour cell lines sensitive and resistant to the experimental cancer drug RH1. We have identified and quantitated over 7 000 proteins; over 500 protein quantity changed 1.5 times and more. These proteins were analyzed by various bioinformatics tools and clustered into functional groups that represent biological processes. A few new biological processes were found to be attributed to the drug resistance.

MAIN R&D&I (RESEARCH, DEVELOPMENT AND INNOVATION) PARTNERS

Swiss Institute of Bioinformatics, Geneva (Switzerland)
Regionshospitalet Viborg, Skive (Denmark)
Schepens Eye Research Institute, Harvard Medical School, Boston (USA)

OTHER SCIENTIFIC ACTIVITIES

Dr. M. Valius –

  • editorial board member of the journal MAP Kinases.

DEPARTMENT OF BIOLOGICAL MODELS

12 Mokslininkų, LT-08662 Vilnius
Tel. 272 9540, fax 272 9196
E-mail:

Head – Dr. Virginija Bukelskiene

STAFF

Senior research fellow: Dr. V. Bukelskiene.
Research fellow: Dr. D. Baltriukiene.
Junior research fellow: Rasa Jarasiene.
Assistants: D. Kulbiene, V. Untaniene, L. Vaskeviciene.

RESEARCH INTERESTS

Laboratory animals for cellular technologies
Stem cell biology

RESEARCH PROJECTS CARRIED OUT IN 2013

Projects Supported by University Budget

Study of the Mechanisms of Eukaryotic Cell Proliferation, Differentiation and Apoptosis (Joint project with Department of Molecular Cell Biology and Proteomics Centre; headed by prof. R. Navakauskienė). 2011–2015.

Study of JNK signalling in blood-derived cells after the effect with natural toxins. Dr. V. Bukelskiene.

JNK signalling was studied in natural toxin ochratoxin A-induced apoptosis in permanents blood and renal as well as hepatic cells. The data obtained show that blood cells are more than 10 times sensitive to the tested mycotoxin treatment than other studied cells. The role of JNK kinase was also evaluated.

Projects supported by the European Social Fund

Participation in the project supported by the European Social Fund under National Integrated Programme Biotechnology & Biopharmacy, grant VP1-3.1-SMM- 08-K01-005. 2012-2015. Action 1.1.3. Molecular processes in eukaryotic cells: the technological and medical aspects (Head of Action Prof. Dr. R. Navakauskiene).

Biocompatibility of various polymeric scaffolds was tested, differentiation and proliferation of adult stem cells grown on the laser microstructured scaffolds was evaluated.

Main publications:

Baltriukienė, D. , Sabaliauskas, V., Balčiūnas, E.,. Melninkaitis, A., Liutkevičius, E., Bukelskienė, V., Rutkūnas, V., 2013. The effect of laser-treated titanium surface on human gingival fibroblast behavior. Journal of Biomedical Materials Research A. doi: 10.1002/jbm.a.34739.

Danilevičius, P., Rekštytė, S., Balčiūnas, E., Kraniauskas, A., Širmenis, R., Baltriukienė, D., Bukelskienė, V., Gadonas, R., Sirvydis, V., Piskarskas, A., Malinauskas, M., 2013. Laser 3D micro/nanofabrication of polymers for tissue engineering applications. Optics and Laser Technology, 45, 518–524.

Kalvelytė, A., Krestnikova, N., Stulpinas, A., Bukelskienė, V., Bironaitė, D., Baltriukienė, D.,Imbrasaitė, A., 2013. Long-term muscle-derived cell culture: multipotency and susceptibility to cell death stimuli. Cell Biology International, 37, 292 –304.

Participation in Global grant under the European Union Structural Funds programme - Molecular Mechanisms of Toxicity and Antitumour Activity of Quinones and Polyphenols: Qsars in the Enzymatic Redox Reactions and Cytotoxicity, Signal Transduction, and Proteomics (VP1-3.1-ŠMM-07-K-01-103). Habil. Dr. N. Čenas. 2011–2015.

Quinone RH-1-resistant cells were prepared; cell cycle analysis of thease cells was performed.

Contractual Research

Water Quality Impact on Female Rats and Embryogenesis and Physical Condition of their Offspring, CJSC Vandens tyrimai, Dr. V. Bukelskiene.

Study of Hemoproliferative Activity, CJSC Profarma, Dr. V. Bukelskiene.

Study of Biological Activity/Toxicity of Substance ECOTO L, private contract, Dr. D. Baltriukiene.

MAIN R&D&I (RESEARCH, DEVELOPMENT AND INNOVATION) PARTNERS

Vilnius University, Faculty of Physics, Laser Research Centre (Lithuania)
Vilnius University, Hospital Santariškių klinikos, Centre of Heart Surgery (Lithuania)
Vilnius Gediminas Technical University, Faculty of Fundamental Sciences, Department of Chemistry and Bioengineering
Vilnius University Institute of Oncology
CJSC Prodentum
CJSC Profarma

OTHER SCIENTIFIC ACTIVITIES

Dr. V. Bukelskienė –

Dr. D. Baltriukiene –