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 - Dr. Kastis Krikštopaitis

STAFF

63 research fellows (49 holding research degree), 18 doctoral students.

 

RESEARCH AREAS

Signalling Pathways and Epigenetic Regulation in Cancer and Stem Cells
Investigation and Application of Biocatalysts and Self-assembled Structures

DOCTORAL DISSERTATIONS MAINTAINED IN 2014

J. Stankevičiūtė. Synthesis of polyhydroxylic compounds by biocatalytic methods.

DEPARTMENT OF BIOANALYSIS

12 Mokslininku, LT-08662 Vilnius
Tel. 272 9068, fax 2729196
E-mail:

Head – Prof. Habil. Dr. Valdas Stanislovas Laurinavičius

STAFF

Chief research fellows, professors: Habil. Dr. V. Laurinavičius (part-time), Habil. Dr. V. Razumas (part-time), Habil. Dr.  J. Kulys (part-time).
Senior research fellows: Dr. J. Razumienė, Dr. R. Šimkus, Dr. R. Vidžiunaitė.
Research fellows: Dr. B. Kurtinaitienė, Dr. L. Tetianec.
Junior research fellows: I. Bratkovskaja, Dr. M. Dagys, V. Gurevičiene.
Doctoral students: A. Chaleckaja, A. Laurynėnas, I. Šakinytė.
Assistants: A. Jonuška, N. Baluckienė, L. Giniotienė, J. Matulevič.

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 PROJECTS CARRIED OUT IN 2014

Project Supported by University Budget

Biocatalytic Systems for Analysis and Synthesis. Prof. Habil. Dr. V. Laurinavičius. 20112016.

The main objectives included the following issues: investigation of catalytic properties and specificity of the oxidoreductases and application in biosensors and bioreactors; construction of nanonobiocatalytic systems; investigation of mechanisms of bacterial self-organization; mathematical modeling of biosensors, bioreactors and cell systems. 
The biocatalytical systems of alcohols oxidation catalysed by NAD+ dependent dehydrogenase were investigated. The diazocompounds were used as mediators for the systems. The dehydrogenase cofactor – NAD+ – regeneration was performed using the mediator that was oxidised electrochemicaly or by laccases.

Main publications:

Tetianec, L., Chaleckaja, A., Vidžiūnaitė, R., Kulys, J., Bachmatova, I., Marcinkevičienė, L., Meškys, R. 2014. Development of a laccase/syringaldazine system for NAD(P)H oxidation. Journal of Molecular Catalysis. B: Enzymatic, vol. 101, 2834.

Stankevičiūtė, J., Kurtinaitienė, B., Stankevičiūtė, R., Meškienė, R., Gasparavičiūtė, R., Marcinkevičienė, L., Laurinavičius, V., Meškys, R. 2014. Prussian blue as an alternative to catalase: a bioelectrocatalytic system for production of dihydroxyacetone phosphate. Chemija, 25(2), 115118.

Dagys, M., Lamberg, P., Shleev, S., Niaura, G., Kulys, J., Arnebrant, T., Ruzgas, T. 2014. Comparison of bioelectrocatalysis at Trichaptum abietinum and Trametes hirsuta laccase modified electrodes. Electrochimica Acta, 130, 141147.

National Research Projects

Research Council of Lithuania.Bee Products Enriched with Plant Components, the Composition and Properties. Grant No.SVE-01/2012. Dr. B. Kurtinaitiene. 20122015.

We produced different composition honey mixtures enriched with vegetable oils and algae.Antioxidant activity, phenolics and flavonoids content, enzymes, fatty acids and other components were investigated in these mixtures. We also conducted an analysis of the dynamic on the changes of composition and other parameters via different storage conditions.

Main publications:

Čeksterytė, V., Kurtinaitienė, B., Jansen, E., Belova, O. 2014. Melissopalynological analysis and biochemical assessment of the nectariferous plants in Lithuania. Baltic Forestry, 2(20), 218229.

Treigytė, G., Zaikova, I., Matuzevičius, D., Čeksterytė, V., Dabkevičienė, G., Kurtinaitienė, B., Navakauskienė, R. 2014.Comparative proteomic analysis of pollen of Trifolium pratense, T. alexandrinum and T. repens. Žemdirbystė-Agriculture, 101(4), 453460.

Research Council of Lithuania.Self-Organization of E. coli and their Mutants near Three Phase Contact Line. (No.MIP-001/2014). Dr. R. Šimkus.

We employed bioluminescence imaging to record images of nutrient rich liquid cultures of the lux-gene reporter Escherichia coli and their mutantsin microtiter plate wells. The dependencies of the average number of luminous aggregates (clouds) on the various environmental factors were analyzed. Our results show that optimal (neutral) pH and high aeration rates determine the highest mean number of clouds, and that spatiotemporal patterns do not form in the pH buffered suspensions. In addition, a sigmoidal dependence of the number of aggregates on the rate of aeration was observed.

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. 2012–2015. Action 1.1.4. Creation of Biocatalysts and Biocatalytic Processes for Bioconversion of Carbohydrates. Head of Action Dr. J. Razumiene.

The carbon materials prospective to be employed in the reagentless biosensing systems, which are able to operate on the principle of the DET, have been discovered. 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. Further such products have been tested as the electrode material for the amperometric biosensors working with pyrroloquinoline quinone dependent glucose dehydrogenase, urease or fructose dehydrogenase.

Main publications:

Razumiene, J., Cirbaite, E., Razumas, V., Laurinavicius, V. 2015. New mediators for biosensors based on PQQ-dependent alcohol dehydrogenases. Sensors & Actuators: B. Chemical, 207, 10191025. doi:10.1016/j.snb.2014.10.050.

Barkauskas, J., Dakševič, J., Budrienė, S., Razumienė, J., Šakinytė, I. 2014. Adhesion of graphene oxide on a transparent PET substrate: a study focused on the optimization process. Journal of Adhesion Science and Technology, 28(20), 20162031.

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, 20122014. Head of the Part of VU Prof. Habil. Dr. V. Laurinavičius.

Food Safety and Food Safety Assessment training courses were translated into Lithuanian language and distributed among food producers. Seminars about modern methods in bioanalysis and food safety assessment were organized for the students of Vilnius University and the specialists of the State Forensic Medicine Service under the Ministry of Justice of Lithuania.

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

Vilnius Gediminas Technical University (Lithuania)
Gaziantep University (Turkey)
Malmo University (Sweeden)

OTHER SCIENTIFIC ACTIVITIES

Prof. Habil. Dr. V. Laurinavičius –

  • member of the Lithuanian Academy of Sciences;
  • editorial boards member of the journalsChemija (Chemistry); Nonlinear Analysis: Modelling and Control; Journal of Theoretical Chemistry;
  • board member of the Lithuanian Biochemical Society.

Prof. Habil. Dr. V. Razumas –

  • President of the Lithuanian Academy of Sciences;
    Chairman of the Lithuanian Science Awards Commission;.
  • board member of the ResearchCouncil of Lithuania.

Prof. Habil. Dr. J. Kulys –

  • member of the Lithuanian Academy of Sciences;
  • member of Europe Biotechnology Federation, Europe Applied Biocatalysis Association, Lithuanian Biotechnology Association, and Lithuanian Biochemical Society;
  • editor of the journal of Biosensors & Bioelectronics;
  • editorial boards member 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 Vilnius
Tel. 272 9186, fax  2729196
E-mail:

Head – Dr. Gintaras Valinčius

STAFF

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

RESEARCH  INTERESTS

Spectroelectrochemistry of proteins and biologically relevant redox species
Self-organization in lipid systems
Membranes/protein (peptide) interactions
Measurement techniques and experimenta data analysis

RESEARCH PROJECTS CARRIED OUT IN 2014

Projects Supported by University Budget

Spectroelectrochemical Studies of Biological Systems and their Models. Dr. G. Valinčius. 20112015.

Main publications:

Dagys, M., Lamberg, P., Shleev, S., Niaura, G., Bachmatova, I., Marcinkeviciene, L., Meskys, R., Kulys, J., Arnebrant, T., Ruzgas, T. 2014. Comparison of bioelectrocatalysis at Trichaptum abietinum and Trametes hirsuta laccase modified electrodes. Electrochim. Acta, 130, 141147.

Sostarecz, A.G., Gaidamauskas, E., Distin, S., Bonetti, S.J., Levinger, N.E., Crans, D.C. 2014. Correlation of insulin-enhancing properties of vanadium-dipicolinate complexes in model membrane systems: phospholipid langmuirmonolayers and AOT reverse micelles. Chem.-Eur. J., 20, 51495159.

Krikštolaitytė, V., Lamberg, P., Toscano, M.D., Silow, M., Eicher-Lorka, O., Ramanavičius, A., Niaura, G., Abariūtė, L., Ruzgas, T., Sleev, S., 2014. Mediatorless carbohydrate/oxygen biofuel cells with improved cellobiose dehydrogenase based bioanode. Fuel Cells, 14(6), 792800.

National Research Projects

Research Council of Lithuania. Molecular Mechanisms of Alzheimers Pathogenesis. Joint project with Lithuanian University of Health Sciences headed by Dr. R. Morkunienė (LIG-04/2012). 20122014.

Main publications:

Ragaliauskas, T., Mickevicius, M., Budvytyte, R., Niaura, G., Carbonnier, B., Valincius, G., 2014. Adsorption of beta-amyloid oligomers on octadecanethiol monolayers. J Colloid Interface Sci., 425, 159167.

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. Valinčius. 20132015.

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

Lithuanian University of Health Sciences, Institute of Neurosciences, Kaunas (Lithuania)
Centre for Physical Sciences and Technology, Institute of Chemistry, Vilnius (Lithuania)
University of Maryland, Institute for Biosciences and Biotechnology Research, Rockville, MD (USA)
Carnegie Mellon University, Pittsburgh, PA (USA)
NIST Centre for Neutron Research, Gaithersburg, MD (USA)
Department of Biomedical Sciences, Faculty of Health and Society, Malmö University, Malmö (Sweden)

OTHER SCIENTIFIC ACTIVITIES

Dr. G. Valinčius –

  • editorial board member of the journal Chemija(Chemistry);
  • member of the Lithuanina Biophysical Society;
  • member of the Lithuanian Biochemical Society;
  • member of the Electrochemical Society (USA).

Habil. Dr. G.Niaura –

  • member of the Lithuanian Academy of Sciences;
  • editorial board member of the journal Chemija(Chemistry);
  • member of the International Society of Electrochemistry.

Dr. R.Budvytytė –

  • member of the American Biophysical Society.

DEPARTMENT OF BIOLOGICAL MODELS

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

Head Dr. Virginija Bukelskiene

STAFF

Senior research fellows: Dr. V. Bukelskienė, Dr. D. Baltriukienė.
Junior research fellow: R. Jarašienė.
Assistants: D. Kulbienė, V. Untanienė, L. Vaškevičienė.
Doctoral students: M. Pečiukaitytė, E. Balčiūnas.

RESEARCH INTERESTS

Laboratory animals, cell culture, stem cells, tissues engineering

RESEARCH PROJECTS CARRIED OUT IN 2014

Projects Supported by University Budget

Cell Technologies for the Regenerative Medicine: Development and Evaluation using Biological Models. Dr. V. Bukelskienė. 20142018.

The study of cell interactions with natural and synthetic scaffolds.
In the studies of cell interactions with synthetic scaffolds, rabbit’s myogenic cell adhesion intensity on various microstructured scaffolds was investigated. Stem cell differentiation was one of the studied parametersthat are likely to affect cell adhesion on the tested scaffolds. However, according to our data, myogenic progenitor cell differentiation toward the osteogenic and myogenic lineages had no impact on the adhesion of tested cells.  The effect of Akt kinase on cellular proliferation and adhesion on different substrates were studied. The results show that increased expression of Akt improved early myogenic cell adhesion, but did not have any significant influence on later.

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. 20122015. Action 1.1.3. Molecular Processes in Eukaryotic Cells: The

Technological and Medical Aspects. (Head of Action - Prof. Dr. R. Navakauskienė).
The microporous structures out of polylactic acid (PLA) were manufactured using 3D printing. All our engineered scaffolds have demonstrated biocompatibility and were suitable for the primary myogenic and endhotelial stem cell growth. The results show that the myogenic progenitor cells fully-filled and homogeneously colonized scaffolds which pore size was about 400 µm. In addition, myogenic cells intensively differentiated into osteoblasts on these porous scaffolds. Comparable research has been carried out with the endothelium-derived progenitor cells; however, a similar effect was not observed.

Main publications:

Malinauskas, M., Rekštytė, S., Lukoševičius, L., Butkus, S., Balčiūnas, E., Pečiukaitytė, M., Baltriukienė, D., Bukelskienė, V., Butkevičius, A., Kucevičius, P., Rutkūnas, V., Juodkazis, S. 2014. 3D microporous scaffolds manufactured via combination of fused filament fabrication and direct laser writing ablation. Micromachines, 5, 839858.

National Research Projects

Research Council of Lithuania.Molecular Mechanisms of Toxicity and Antitumour Activity of Quinones and Polyphenols: Enzymatic Redox Reactions, Cytotoxicity, Signal Transduction and Proteomics (VP1-3.1-ŠMM-07-K01-103, Global grant); Head - habil.dr. N. Čėnas. 20112015.

The mode of action of tetramethyl-1,4-benzoquinone (DQ), 2,5-diaziridinyl-3,6-dimethyl-1,4-benzoquinone (MeDZQ), and 2,5-diaziridinyl-3-(hydroxymethyl)-6-methyl-1,4-benzoquinone (RH1) were analysed. We have found that in the MH-22A cell culture, quinones MeDZQ and RH1 caused only apoptotic cell death, whereas DQ induced both necrosis and apoptosis. Antioxidants DPPD and DFOA protected the cells against the action of tested quinones. This effect demonstrated possible role of oxidative stress in the quinones induced cell death process. The role of stress-activated protein kinases p38 and JNK were elucidated.

Research Council of Lithuania. Significance of Titin Ligands Murf and C ARP in Dilated Myocardium. MIP-011/2014; Head - Prof. Habil. Dr. V. Grabauskienė (VU Faculty of Medicine). 20142016.
We have evaluated the clinical potential of titin ligands in monitoring progression of cardiac remodeling associated with end-stage idiopathic dilated cardiomyopathy (IDCM). Expression patterns of 8 mechanoptotic machinery-associated titin ligands (among which is ligand ANKRD1) were quantitated in endomyocardial biopsies from patients with advanced IDCM. On molecular level, myocardial ANKRD1 and serum adiponectin correlated with low BAX/BCL-2 ratios, indicative of antiapoptotic tissue propensity observed during the worsening of heart failure. The association of ANKRD1 with antiapoptotic response suggests its role as myocyte survival factor during the late stage heart disease.

Main publications:

Bogomolovas, J., Brohm, K., Čelutkienė, J., Balčiūnaitė, G., Bironaitė, D., Bukelskienė, V., Daunoravičus, D., Witt, Ch.C, Fielitz, J., Grabauskienė, V., Labeit, S. 2014. Induction of Ankrd1 in dilated cardiomyopathy correlates with the heart failure progression. BioMed Research International (formerly titled Journal of Biomedicine and Biotechnology).  Article ID 273936.

Agency for Science, Innovation and Technology. Co-operation between business and research institutions Innovation Voucher, projects:

Evaluation of the Biocompatibility of Scaffolds Designed for Bone Formation. CCAudronės odontologijos gydykla. Dr. V. Bukelskienė.

Assessment of the Chronic Toxicity of Drinking Water “Melt Water Original”. Research and Production Company Melt Water(LT). Dr. D. Baltriukienė.

Contractual Research

To Assess Feed Additives Acute, Chronic or Repeated Doses Toxic Effect by Using Laboratory Mice. CC Centrinis parkas. Dr. V. Bukelskienė.
Study of Hemoproliferative Activity. CC Profarma. Dr. V. Bukelskienė.
Evaluation of the Most Active Microorganism Susceptibility and Toxicity for Warm-blooded Animals. Nature Research Centre. Dr. V. Bukelskienė.

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

Vilnius University, Faculty of Physics, Laser Research Centre (Lithuania)
Vilnius University, Faculty of Chemistry (Lithuania)
Vilnius University, Faculty of Medicine (Lithuania)
Vilnius University, Hospital Santariškių klinikos, Centre of Heart Surgery (Lithuania)
Vilnius University, Faculty of Medicine, Institute of Odontology (Lithuania)

OTHER SCIENTIFIC ACTIVITIES

Dr. V. Bukelskienė –

Dr. D. Baltriukienė –

DEPARTMENT OF BIOORGANIC COMPOUNDS CHEMISTRY

12A Mokslininkų, LT-08662 Vilnius
Tel. 2729058, fax 2729196
E-mail:

Head – Dr. Regina Jančienė

STAFF

Senior research fellow: 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 2014

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. 20142016.

Investigation of the synthesis of cyclic polyethers bearing disubstituted cyclohexane moiety
Study of the usage of various protecting groups for the synthesis of polyethylene glycol oligomers
Synthesis of new tricyclic fused 1,5-benzodiazepine derivatives
The alkylation of dibenzo-18-crown-6 with t-butanol was investigated and a new method for 4’,4’’(5’’)-di-tert-butyl-dibenzocrown synthesis was developed. Optimal reaction conditions of the hydrogenation of dibenzoderivatives were established.
The synthesis of 1-(3-nitrophenyl)-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepines was investigated. These compounds were synthesized by the thermal cyclization of corresponding benzodiazepine-2-nitrobenzohydrazide derivatives which were obtained from 1,5-benzodiazepin-2-thiones.

Main publications:

Janciene, R., Mikulskiene, G., Javorskis, T., Vektariene, A., Vektaris, G., Kosychova, L. 2014. Dihydroquinazolino[3,2-a][1,5]benzodiazepines: synthesis and computational study of reductive N-heterocyclization of N-(2-nitrobenzoyl)-1,5-benzodiazepin-2-ones. Journal of Heterocyclic Chemistry,doi:10.1002/jhet.2038.

Butkus, S., Paipulas, D., Sirutkaitis, R., Gaižauskas, E., Sirutkaitis, V. 2014. Rapid cutting and drilling of transparent materials via femtosecond laser filamentation. JLMN-Journal of Laser Micro/Nanoengineering, 9(3), 213220.

National Research Projects

Agency for Science, Innovation and Technology.National program to support R&D contracts.
Synthesis of Pantetine-4‘,4‘‘-Diphosphate and other Enzyme Cofactors.
Research in Development of New Methods for Monobenzylation of Diols
Study of the Synthesis of Aromatic and Cyclohexane Carboxylic Acid Derivatives. Dr. A. Palaima. 2014.
Methods of synthesis of pantethine-4',4''-diphosphate were developed, reaction conditions of separate steps were optimized, developed technology was applied for the preparative synthesis and the experimental batches were prepared. Method of benzylation of nonaethylene glycol was developed and experimental batches suitable for the further syntheses were prepared. Stereospecific conditions of catalytic hydrogenation of nitrobenzoic acid derivatives were investigated and experimental batches of cyclohexanecarboxylic acid derivatives were prepared.

Contractual Research

Study of Synthesis Optimization of Pantetine-4‘,4‘‘-Diphosphate and other Enzyme Cofactors. CC Thermo Fisher Scientific Baltics. Dr. A. Palaima.

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

Study of the Synthesis of Indole Derivatives Containing Amidine Group. CC Biotecha. Dr. R. Jančienė.

Research in Development of New Methods for Monobenzylation of Diols. Ramidus AB (Sweden). Dr. A. Palaima.

Study of the Synthesis of Aromatic and Cyclohexane Carboxylic Acid Derivatives. Bapeks SIA (Latvia). Dr. R. Jančienė.

Synthesis of 4-Methyl-1-Tetralone and Dicyclohexyl-18-Crown-6. Synthon Chemicals GmbH (Germany). Dr. R. Jančienė.

Synthesis of 1,3-Dithiane. Admiral Chemicals LLC (USA). Dr. R. Jančienė.

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

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

DEPARTMENT OF MOLECULAR CELL BIOLOGY

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

Head – Prof. Dr. Rūta Navakauskienė

STAFF

Chief research associate: Prof. Dr. R. Navakauskienė.
Senior research fellow: Dr. A. Kalvelytė.
Research fellows: Dr. G. Treigytė, Dr. J. Savickienė, Dr. V. V. Borutinskaitė, Dr. A. Imbrasaitė.
Junior research fellows: A. Stulpinas, Dr. N. Krestnikova, I. Zaikova.
Doctoral students: S. Baronaitė, G. Valiulienė (Vištartaitė).

RESEARCH INTERESTS

Studies of molecular mechanisms in normal and cancer cells to determine new possibilities of leukemia differentiation therapy
Epigenetic regulation in cancer and stem cells
Studies of apoptosis signaling in cancer and adult stem cell models in vitro, stem cells in cell therapy and drug testing

RESEARCH PROJECTS CARRIED OUT IN 2014

Projects Supported by University Budget

Studies of Regulatory Mechanisms of Cancer and Stem Cell for New Technologies of Personalized Medicine. Prof. R. Navakauskienė. 20142018.

Studies of signaling molecules regulating tumor suppressor p53 expression and phosphorylation in the stem cells models and cancer cells treated with anticancer agents were carried out.

Main publications:

Savickiene, J., Treigytė, G., Stirblyte, I., Valiuliene, G., Navakauskienė, R., 2014. Euchromatic histone methyltransferase 2 inhibitor, BIX-01294, sensitizes human promyelocytic leukemia HL-60 and NB4 cells to growth inhibition and differentiation. Leukemia Research, 38 (7), 822829.

Savickiene, J.,Treigytė, G., Valiuliene, G., Stirblyte, I., Navakauskienė, R., 2014.Epigenetic and molecular mechanisms underlying the antileukemic activity of the histone deacetylase inhibitor belinostat in human acute promyelocytic leukemia cells. Anti-Cancer Drugs, 25(8), 938949. doi:10.1097/CAD.0000000000000122.

Krestnikova, N., Stulpinas, A., Imbrasaitė, A., Sinkevičiūtė, G., Kalvelytė, A. JNK implication in adipocyte-like cell death induced by chemotherapeutic drug cisplatin. The Journal of Toxicological Sciences, 40(1) (2015).

National Research Projects

Research Council of Lithuania. Multiplexed Molecular Biomarker Study for Leukemia (No.LIG-06/2012). Prof. R. Navakauskienė. 20122014.

Research Council of Lithuania.Cytological, Molecular and Epigenetic Studies of Amniotic Fluid (No. MIP-033/2013) Dr. G. Treigytė. 20132015.

Research Council of Lithuania. National Science program project Bee Products Enriched with Plant Components, the Composition and Properties (No. SVE-01/2012). 20122015.

Research Council of Lithuania.Molecular Mechanisms of Toxicity and Antitumour Activity of Quinones and Polyphenols: Enzymatic Redox Reactions, Cytotoxicity, Signal Transduction and Proteomics (VP1-3.1-ŠMM-07-K01-103, Global grant, Head - Habil. Dr. N. Čėnas, 20112015).

Projects supported by theEuropean 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. 20122015.Action 1.1.3. Molecular Processes in Eukaryotic Cells: the Technological and Medical Aspects. Prof. Dr. R. Navakauskienė.

International Research Projects

COST Action CM1106: Chemical Approaches to Targeting Drug Resistance in Cancer Stem Cells (Stemchem). Prof. R. Navakauskienė. 20122016.

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

Linkoping University (Sweden)
Nice University (France)
Milan University (Italy)

DEPARTMENT OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY

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

HeadDr. Rolandas Meškys

STAFF

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

RESEARCH INTERESTS

Molecular biology and genetics of bacteria and bacteriophages
Genetic and biochemical diversity of microorganisms, enzyme biotechnology

RESEARCH PROJECTS CARRIED OUT IN 2014

Projects Supported by University Budget

Investigation of Genetic and Biochemical Diversity of Bacteriophages and Microorganisms Bacteriophages. Dr. R. Meškys. 20142018.

Studies of microbial oxidoreductases and arthrobacterial bacteriophages

Several biocatalytic processes based on laccases, oxydases as well as hydrolases have been developed for synthesis of modified oligosaccharides and dihydroxyacetone phosphate, and regeneration of cofactors. The optimization and analysis of these biocatalytic conversions was cariied out.
Bacteriophages ArV1 and ArV2 were isolated from soil using Arthrobacter sp. 68b for phage propagation. Based on transmission electron microscopy, ArV1 belongs to the family Myoviridae and has an isometric head (80 nm), a contractile tail (150×30 nm), a baseplate, and short tail fibers. Phage ArV2 is morphologically similar to phages of the family Siphoviridae, and has an isometric head of 60 nm and a non-contractile tail of 190 nm by 10 nm. The genome sequence of ArV2 was determined using HiSeq 2000 DNA sequencing technology. Analysis of the draft genome sequence (37.4 kb; 63% G+C) of siphovirus ArV2 allowed identification of 70 ArV2 probable protein-encoding genes, of which 17 encode unique proteins that have no homologs in databases. Among the ORFs that encode proteins with matches to those in other sequenced genomes, 27 are similar to proteins from viruses that infect Mycobacterium, Rhodococcus, Propionibacterium and other bacteria, while another 27 are most similar to proteins from Bacteria.  Proteomic analysis of the structural ArV2 proteins separated by SDS PAGE led to the experimental identification of 15 virion proteins, including 7 that were predicted by bioinformatics approaches, and 8 unique gene products that have no reliable homologues to annotated structural proteins in other organisms.

Main publications:

Tetianec, L., Chaleckaja, A., Vidziunaite, R., Kulys, J., Bachmatova, I., Marcinkeviciene, L., Meskys, R. 2014. Development the laccase/syringaldazine system for NAD(P)H oxidation. J. Mol. Catal. B: Enzym, 101, 2834. doi:10.1016/j.molcatb.2013.12.013.

Dagys, M., Lamberg, P, Shleev, S., Niaura, G., Bachmatova, I., Marcinkeviciene, L., Meskys, R., Kulys, J., Arnebrant, T., Ruzgas, T. 2014. Comparison of bioelectrocatalysis at Trichaptum abietinum and Trametes hirsuta laccase modified electrodes. Electrochimica Acta, 130,141–147.

Sulcius, S., Simoliunas, E., Staniulis, J., Koreiviene, J., Baltrusis, P., Meskys, R., Paskauskas, R. 2014. Characterization of a lytic cyanophage that infects the bloom-forming cyanobacterium Aphanizomenon flos-aquae.FEMS Microbiol. Ecol. doi:10.1093/femsec/fiu012./s00705-013-1800-x

National Research Projects

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 have been collected, new potential substrates for these enzymes have been prepared, new inducible promoters including of the ones from bacteriophages applicable for non-standard hosts have been identified and characterized. Novel oxygenases screening system has been developed. Novel Baeyer-Villiger monooxygenases have been identified and their encoding genes have been cloned by using substrates prepared during this study.

Main publications:

Šimoliūnas, E., Kaliniene, L., Stasilo, M., Truncaitė, L., Zajančkauskaitė, A., Staniulis, J., Nainys, J., Kaupinis, A., Valius, M., Meškys, R. 2014. Isolation and characterization of vB_ArS-ArV2 – first Arthobacter sp. infecting bacteriophage with completely sequenced genome. PLoS One9(10): e111230. doi:10.1371/journal.pone.0111230.

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

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 the following results were obtained in 2014:the mutagenesis of the previously cloned six archaeal genes, involved in the biosynthesis of the wyosine derivatives, was carried out; the enzymatic activity of the mutant proteins was analysed.

Main publications:

Urbonavičius, J., Meškys, R., Grosjean, H. 2014. Biosynthesis of wyosine derivatives in tRNAPhe of Archaea: role of aremarkable bifunctional tRNAPhe:m1G/imG2 methyltransferase. RNA 20:747–753.

Research Council of Lithuania. Adaptation of Invasive Species and their Impact on Aquatic Ecosystems of Different Complexity (LEK-10/2012). Dr. R. Meškys. 2012–2014.

This project aims at investigating adaptation of invasive species and their impacts on aquatic ecosystems. For the first time oxygenases producing microoorganisms were isolated from intestine microflora of two crayfish species. The corresponding genes were cloned and analysed.

Research Council of Lithuania. Proteogenomics of the Early Infection Stages of Virulent Escherichia Coli Bacteriophages (MIP-002/2014). Dr. L. Truncaitė. 2014–2016.

Complete genome sequence of the Escherichia coli bacteriophage vB_EcoM_VpaE1 (VpaE1) have been determined and submitted to NCBI GenBank database. Proteins of the early infection stages of VpaE1 have been identified using mass spectrometric analysis of the total proteome of infected cells. Transcripts of the early genes have been investigated by primer extension analysis. Several genes encoding proteins of unknown function of phages VpaEI and T4 have been cloned and expressed in the E. coli expression strains.

Contractual Research

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)

DEPARTMENTS OF XENOBIOTICS BIOCHEMISTRY1 AND SCIENTIFIC INFORMATION2

12 Mokslininkų, LT-08662 Vilnius
Tel.: 272 90421, 272 91952, fax 272 9196
E-mail: 1, 2

Heads – Habil. Dr. Narimantas Čėnas1, Dr. Kastis Krikštopaitis2

STAFF

Chief research fellow: Habil. Dr. N. Čėnas.
Senior research fellows: Dr. Žilvinas Anusevičius, Dr. Kastis Krikštopaitis, Dr. Jonas Šarlauskas.
Research fellows: Dr. Audronė Marozienė, Dr. Gema Mikulskienė, Dr. Valė Miliukienė, Dr. Lina Misevičienė.
Doctoral students: R. Jarašienė, E. Polmickaitė.

RESEARCH INTERESTS

Investigations of the molecular mechanisms of antitumour activity and cytotoxicity of aziridinyl-substituted and –unsubstituted quinones, including the heterocyclic ones, in particular of the impact of their single - and two-electron enzymatic reduction
Investigations of the molecular mechanisms of the prooxidant cytotoxicity of polyphenols in mammalian cells
Investigations of the redox reactions of flavoenzymes with quinoidal, nitroaromatic and other redox active xenobiotics which may cause the cytotoxic and prooxidant events

RESEARCH PROJECTS CARRIED OUT IN 2014

Projects Supported by University Budget

Molecular Mechanisms of Enzymatic Activation, Detoxification, Biodegradation, and Cytotoxicity of Redox Active Xenobiotics. Habil. Dr. N. Čėnas. 20112016.

The reactivity of of benzo[1,2-c]1,2,5-oxadiazole N-oxides (BFX) towards single-electron transferring NADPH:cytochrome P-450 reductase (P-450R) and two-electron transferring NAD(P)H:quinone oxidoreductase (NQO1) was compared to that of nitroaromatic compounds (ArNO2) which possessed the same electron-accepting potency. In P-450R-catalyzed reactions, both BFX and ArNO2 showed the same reactivity dependence on their electron-accepting potency which is consistent with an "outer sphere" electron transfer. In NQO1-catalyzed reactions, BFX were more efficient substrates than ArNO2 due to their ditfferent binding mode.

Main publications:

Šarlauskas, J., Misevičienė, L., Marozienė, A., Karvelis, L., Stankevičiūtė, J., Krikštopaitis, K., Čėnas, N., Yantsevich, A., Laurynėnas, A., Anusevičius, Ž. 2014. The study of NADPH-dependent flavoenzyme-catalyzed reduction of benzo[1,2c]1,2,5-oxadiazole N-Oxides (Benzofuroxans). Int. J. Mol. Sci., 15, 2330723341.

National Research Projects

Research Council of Lithuania. Targeted Synthesis of New Generation N-Heterocyclic Quinones and the Studies of their Antitumour Action (No.MIP-032/2014). Dr. Ž. Anusevičius. 20142016.

Main results of 2014 were as follows: a) 6 new compounds of this group were synthesized; b) their single-and two-electron redox properties in reactions with cytochrome P-450 reductase and DT-diaphorase were determined, and c) their cytotoxicity in MH22a cells was investigated.

Research Council of Lithuania. Molecular Mechanisms of Toxicity and Antitumour Activity of Quinones and Polyphenols: Enzymatic Redox Reactions, Cytotoxicity, Signal Transduction and Proteomics (VP1-3.1-ŠMM-07-K01-103, Global grant). Habil. Dr. N. Čėnas. 20112015.

Both 2e- and 4e-reduced states of pig heart lipoamide dehydrogenase, and its reaction product, dihydrolipoamide, efficiently reduce aziridinyl-substituted anticancer benzoquinones. Thus, lipoamide dehydrogenase/lipoamide system may be considered as their additional source of bioreductive activation in the cell. Polyhydroxybenzenes and flavonoids exhibit the same patterns of prooxidant cytotoxicity in primary cells (splenocytes) as in tumour (transformed) cells. Therefore, they may not be regarded as specific antitumour agents. Antitumour aziridinyl-substituted enzoquinone RH1 exhibits moderately enhanced cytotoxicity in primary mice splenocytes with a low content of DT-diaphorase. Thus, this compound may be not devoid of the significant side-effects in tumour chemotherapy. 

Main publications:

Nivinskas, H., Valiauga, B., Šarlauskas, J., Čėnas, N. 2014.Reduction of aziridinyl-substituted anticancer benzoquinones by lipoamide dehydrogenase. Chemija, 25, 213217.

Miliukienė, V., Nemeikaitė-Čėnienė, A., Čėnas, N. 2014. Prooxidant cytotocity of polyphenolic antioxidants in primary mice splenocytes: the role of redox potential and lipophilicity. Chemija, 25, 218223.

Miliukienė, V., Nivinskas, H., Čėnas, N. 2014. Cytotoxicity of anticancer aziridinyl-substituted benzoquinones in primary mice splenocytes. Acta Biochimica Polonica, vol. 61, 833836.

International Research Projects

COST Action CM1307 Targeted Chemotherapy Towards Diseases Caused By Endoparasites. Dr. J. Šarlauskas, Habil. Dr. N.  Čėnas. 20142017.

Main results: synthesis of 7 nitroheterocyclic compounds, testing of their antileishmanial activity.

Bilateral French-Lithuanian programme Gilibert. Quinones and Nitroaromatic Compounds as the Subversive Substrates of Flavohemoglobins: Mechanisms and Biomedical Implications (No. TAP LZ 07/2013). Habil. Dr. N. Čėnas. 20132014.

Main results: using nonphysiological quinoidal and nitroaromatic electron acceptors, the electron transfer between flavin and heme cofactors in S. aureus flavohemoglobin was thoroughly investigated. The effects of flavohemoglobin inhibitors on the reaction kinetics show that the electrons are accepted from flavin but do not form heme cofactor.

Bilateral Lithuanian-Belarus programme Characterisation of Interprotein Interaction and Transfer of Redox Equivalents in Steroid Hydroxylase Systems (No. TAP LB 02/2013). Dr. Ž. Anusevičius. 20132014.

Main results: the electron transfer from NADPH: cytochrome P-450 reductase and adrenodoxin reductase/adrenodoxin system to novel redox active heterocyclic compounds was quantitatively characterized.

Main publications:

Anusevičius, Ž., Šarlauskas, J., Misevičienė, L., Krikštopaitis, K., Yantsevich, A.V., Dichenko, Y.V. Stankevičiūtė, J., Usanov, S.A., Čėnas, N. 2014. Phenyl-N-methylnitroamines: their preparation, electron- accepting potency and enzymatic reactivity. New Trends in Research of Energetic Materials, 17, Pt.II, 518532.

Bilateral Lithuanian-Ukraine programme Investigation of L- and D-lactate: Cytochrome с Oxidoreductases Isolated from the Recombinant Yeast Hansenula Polymorpha and their Usage for Construction of Amperometric Biosensors (No. TAP LU 03/2014). Dr. K. Krikštopaitis. 20142015.

Main results: flavocytochrome b2from Hansenula polymorpha was purified; the enzyme kinetic properties using ferricyanide (acceptance of electrons from flavin and heme) and cytochrome c (acceptance of electrons from heme) were examined; the mode of enzyme inhibition by the reaction product, pyruvate, was examined; prelimiminary studies of the application of flavocytochrome b2 in the amperometric biosensor for L-lactate were carried out. 

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

Universite de Paris Sud (Orsay) (France)
Universite de Lorraine, Nancy (France)
Pardubice University, Pardubice (Czech Republic)
Institute of Bioorganic Chemistry of Belarus Academy of Sciences, Minsk (Belarus)
Institute of Cell Biology of Ukrainian Academy of Sciences, Lviv (Ukraine)

PROTEOMICS CENTRE

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

Head – Dr. Mindaugas Valius

STAFF

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

RESEARCH INTERESTS

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

RESEARCH PROJECTS CARRIED OUT IN 2014

Projects Supported by University Budget

New Technologies for Tumor Diagnosis and Treatment Based on Nano-Materials and Proteomics. Dr. M. Valius. 20142018.

Main publications:

Karabanovas V., Zitkus Z, Kučiauskas D. Rotomskis R., Valius M. 2014. Surface properties of quantum dots define their cellular endocytic routes, mitogenic stimulation and suppression of cell migration. Journal of Biomedical Nanotechnology, 10(5), 775786 2014. doi: http://dx.doi.org/10.1166/jbn.2014.1770.

Damalakiene L., Karabanovas V., Bagdonas S., Pupelis L., Valius M., Rotomskis R. 2015. Suppression of a specific intracellular uptake pathway by a saturating accumulation of quantum dots.Journal of Biomedical Nanotechnology, 11(5), 841853. doi: http://dx.doi.org/10.1166/jbn.2015.2007

Šimoliūnas E., Kalinienė L., Stasilo M., Truncaitė L., Zajančkauskaitė A., Staniulis J. B., Nainys J., Kaupinis A., Valius M., Meškys R. 2014. Isolation and characterization of vB_ArS-ArV2 - first Arthrobacter sp. infecting bacteriophage with completely sequenced genome. PLoS ONE 9(10), e111230. doi:10.1371/journal.pone.0111230.

National Research Projects

Research Council of Lithuania: High Throughput Proteomics for Cancer Cell Surface Protein Recognition by Quantum Dots (MIP-033/2014). Dr. M. Valius. 20142016.

Cancer treatment leads to the development of the resistance to the therapeutic agent. Here we sought to investigate molecular mechanisms of drug-resistance by proteomics approach, find cancer cell-specific surface proteins and use that knowledge in developing novel visualization techniques of cancer cells and cancer cells unsusceptible to therapy.

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). Head - Habil. Dr. N. Čėnas. 20112015.

We have performed high throughput proteomics analysis of human promyelocytic leukemia cells cell lines sensitive and resistant to the experimental cancer drug RH1. To this end we have identified and quantitated more than different 7000 proteins; ~500 protein were correlated with drug-resistance. Bioinformatics analysis reveals various biological and molecular processes relevant to the molecular mechanism that could contribute to the RH1-resistancy.

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-K01-005.20122015.Action 1.1.3. Molecular Processes in Eukaryotic Cells: The Technological and Medical Aspects. Head of Action - Prof. Dr. R. Navakauskienė, Dr. M. Valius. 20122015.

We have elucidated intracellular enterence and trafficking of nano-particles (quantum dots) in cancer cells and have shown that surface properties of these particles define their biological impact. Results also show that quantum dots might affect the outcome of anti-cancer therapy.

Contractual Research

Study of the effect of various hart conditions on their mitochondria proteome (new technology: high throughput quantitative proteomics). Lithuanian University of Health Sciences, Institute for Biomedical Research, Kaunas (Lithuania).

Study of Apple Proteome. Institute of Horticulture, Lithuanian Research Centre for Agriculture and Forestry Plant Biology, Baptai (Lithuania).

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

Swiss Institute of Bioinformatics, Geneva (Switzerland)
Aargus University, Aargus (Denmark)
Schepens Eye Research Institute, Harvard Medical School, Boston (USA)
Lithuania National Cancer Center, Vilnius (Lithuania)

OTHER SCIENTIFIC ACTIVITIES

Dr. M. Valius –

  • editorial board member of the journal MAP Kinases.