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

62 research fellows (50 holding research degree), 23 doctoral students.

 

RESEARCH AREAS

Signalling Pathways and Epigenetic Regulation in Cancer and Stem Cells

Investigation and Application of Biocatalysts and Self-assembled Structures

 

DEPARTMENT OF BIOANALYSIS

12 Mokslininkų, LT-08662 Vilnius
Tel. 272 9068, fax 272 9196
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, A. Laurynėnas.
Doctoral students: A. Chaleckaja, D. Ratautas, 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 2015

Project Supported by University Budget

Biocatalytic Systems for Analysis and Synthesis. Prof. Habil. Dr. V. Laurinavičius. 2011–2016:

Investigation of catalytic properties and specificity of the oxidoreductases and application in biosensors and bioreactors

Construction of nanonobiocatalytic systems

An investigation of mechanisms of bacterial self-organization

Mathematical modeling of biosensors, bioreactors and cell systems 

The investigation of consecutive enzyme reactions and their application in development of bioanalytical and substrates transformation systems

New mediators (N-hydroxy- compounds, benzodiazepines, phenylenediamine derivatives) and enzymes (laccases and dehydrogenases) were investigated and their catalytic properties, essential for development of bioanalytical and substrate transformation systems, were estimated. 

Main publication:

Kosychova, L., Vidziunaite, R., Mikulskiene, G., Bratkovskaja, I., Janciene, R. 2015. A convenient synthesis and spectral characterization of novel 5,6-dihydro-4H-tetrazolo-[1,5-a][1,5]benzodiazepine derivatives. ARKIVOC, vol. 2, p. 71–87.                                                                                 

Mathematical modeling of biosensors, bioreactors and cell systems

The modelling and fitting of biochemical and chemical kinetics was  investigated. The effective and robust algorithm for rate constants deteremination was created.
Molecular structure and reactivity of enzymes was analysed using the molecular orbitals theory and condensed Fukui functions.

Main publications:

Laurynėnas, A., Kulys, J. 2015. An exhaustive search approach for chemical kinetics experimental data fitting, rate constants optimization and confidence interval estimation. Nonlinear Analysis-Modelling And Control, vol. 20, no. 1, p. 145–157. 

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, 2-c] 1, 2, 5-oxadiazole N-oxides (Benzofuroxans). International Journal of Molecular Sciences, vol. 15, no. 12, p. 23307–23331.

Kosychova, L., Karalius, A., Staniulytė, Z., Sirutkaitis, R. A., Palaima, A., Laurynėnas, A., Anusevičius, Ž. 2015. New 1-(3-Nitrophenyl)-5, 6-dihydro-4H-[1, 2, 4] triazolo [4, 3-a][1, 5] benzodiazepines: synthesis and computational study. Molecules, vol. 20, no. 4, p. 5392–5408.

New matrixes using immobilized enzymes for prospective bioanalytic tools have been created.

Main publication:

Voitechovic, E., Bratov, A., Abramova, N., Razumiene, J., Kirsanov, D., Legin, A.,. Lakshmi, D., Piletsky, S., Whitcombe, M., Ivanova- Mitseva, P.K. 2015. Development of label-free impedimetric platform based on new conductive polyaniline polymer and three-dimensional interdigitated electrode array for biosensor applications. Electrochimica Acta, vol. 173, p. 59–66.

An investigation of mechanisms of bacterial self-organization

We show that bioluminescence imaging can be fruitfully applied to provide new insights into bacterial self-organization. In this work we analyse changes in spatiotemporal patterns of bacterial self-organization, which are induced by the addition of organic solvents to the culture medium. Results show a pronounced effect of the addition of ethyl alcohol. 

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

The carbon materials prospective to be employed in the reagentless biosensing systems, which are able to operate on the principle of the direct electron transfer have been discovered and such products have been tested as the electrode material for the amperometric biosensors working with pyrroloquinoline quinone dependent glucose dehydrogenase, urease or fructose dehydrogenase. It was shown way from carbon modification to analyzer design.

Main publications:

Razumiene, J., Sakinyte, I., Gureviciene, V., Petrauskas, K. 2015. Amperometric Urea Sensor Enzyme Immobilization into Adjustable Membrane and Mathematical Characterization of the Biosensor. Biodevices: 8th international conference on biomedical electronics and devices: proceedings. 2015 SCITEPRESS-science and technology publications, Lisboa, p. 144–149.

Razumiene, J., Sakinyte, I., Gureviciene, V., Jonuska, A. 2015. From carbon modification to analyzer design. International Journal of Emerging Technology and Advanced Engineering, vol. 5 (2) special Issue, p. 19–24.

National Research Projects

Lithuanian Agency for Science, Innovation and Technology. EUREKA Project E! 8835. Multiple Biosensor Device for Hemodialysis Patients. Dr. J. Razumiene.

Aiming to design commercially viable analytical device, detecting urea, sodium and potassium concentrations in blood and biological fluids necessary bioelectrodes have been created on a base of thermally reduced graphene oxide and immobilized enzymes.

Main publication:

Šakinytė, I., Barkauskas, J., Gaidukevič, J., Razumienė, J. 2015. Thermally reduced graphene oxide: The study and use for reagentless amperometric D-fructose biosensors. Talanta, vvol. 144, p. 1096–1103.

Research Council of Lithuania. Bee Products Enriched with Plant Components, the Composition and Properties. Grant No. SVE-01/2012. Dr. B. Kurtinaitiene 2012–2015.

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.  

Contractual Research

Applied science project Amperometric Fast Response Method for Measurement of Urea Concentration in Industrial Media, funded by Charity and Support Foundation of Dr. Bronislovas Lubys. head – Dr. Marius Dagys, partner – Vidutė Gurevičienė. 2015–2016.

An amperometric urea biosensor system is to be adapted to measurement of urea in industrial production and waste media obtained from nitrogen fertilizer production plant “Achema”. The activities involve improvement of current urea biosensor technology with respect to insensitivity to reactive compounds present in industrial media, also redesign of current urea amperometric cell and electronic measurement system.

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

Vilnius Gediminas Technical University (Lithuania)
Gaziantep University (Turkey)
Malmo University (Sweeden)
Institute of Molecular Biology and Genetics of the National Academy of Science (Ukraine)
CC Bioanalizės sistemos (Lithuania)
CC Ubique calculus (Lithuania)

OTHER SCIENTIFIC ACTIVITIES

Prof. Habil. Dr. V. Laurinavičius – 

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

Prof. Habil. Dr. V. Razumas –

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

Prof. Habil. Dr. J. Kulys –

  • member of the Lithuanian Academy of Sciences;
  • member of the Research Council of Lithuania;
  • member of Europe Biotechnology Federation, Europe Applied Biocatalysis Association, Lithuanian Biotechnology Association and Lithuanian Biochemical Society;
  • editor-in-chief of the journal Biosensors & Bioelectronics;
  • editorial boards member of: The Open Nanoscience Journal, The Open Enzyme Inhibition Journal, The Open Biotechnology Journal, Biologija, Nonlinear analysis, Modelling and Control.

 

DEPARTMENT OF BIOELECTROCHEMISTRY AND BIOSPECTROSCOPY

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

Head – Dr. Gintaras Valinčius

STAFF

Chief research fellows: Dr. G. Valinčius, Habil. Dr. G. Niaura.
Senior research fellow: Dr. Giulio Preta.
Research fellow: Dr. M. Jankunec.
Junior research fellows: Dr. A. Bulavas, Dr. R. Budvytytė, Dr. B. Rakovska.
Specialists: T. Ragaliauskas, M. Mickevičius, M. Talaikis.
Doctoral students: I. Aleknavičienė, J. Latynis, T. Penkauskas.

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 2015

Project Supported by University Budget

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

Using reflection absorption and surface plasmon resonance spectroscopies along with the electrochemical detection of enzymatic rates, we found that crowding of ester bond cleaving enzymes sharply accelerates enzymatic digestion rates. This effect was explained by self-organization of enzyme molecules driven by increased surface concentration (activity), during which favourable orientation of enzyme with respect to its target group is achieved.

Main publication:

Balevičius, Z., Ignatjeva, D., Niaura, G., Ignatjevas, I., Vaičikauskas, V., Babonas, G. J., Valincius, G. 2015. Crowding enhances lipase turnover rate on surface immobilized substrates. Colloids and Surfaces: Biointerfaces, vol. 131, p. 115–121.

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. 2013–2015.

Project aimed at designing and laboratory testing of phospholipid bilayers for detection of bacterial virulence factors that impairs integrity of the artificial membranes. A study of the electrochemical impedance response to a pore-forming toxins revealed several important diagnostic criteria that may be used for the interpretation and quantitative estimates of pathogens from the EIS measurements.

Main publications:

Valincius, G., Mickevicius, M. 2015. Tethered phospholipid bilayer membranes: an interpretation of the electrochemical impedance response. In: Advances in Liposomes and Planar Bilayers, vol. 21, Chapter IV.

Rakovska, B., Ragaliauskas, T., Mickevicius, M., Jankunec, M., Niaura, G., Vanderah, D.J., Valincius, G. 2015. Structure and function of membrane anchoring self-assembled monolayers. Langmuir, vol. 31, p. 846–857. 

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

Lithuanian University of Health Sciences, Institute of Neurosciences, Kaunas (Lithuania)

Center 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 Center 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;
  • 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;
  • 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. Alksnė (Pečiukaitytė), E. Balčiūnas.

RESEARCH INTERESTS

Laboratory animals, cell culture, stem cells, tissues engineering

RESEARCH PROJECTS CARRIED OUT IN 2015

Project Supported by University Budget

Cell Technologies for Regenerative Medicine: Development and Evaluation. Dr. V. Bukelskienė. 2014–2018.

Study of cell interactions with natural and synthetic scaffolds.

Material biocompatibility depends on numerous factors including the nature of the material, its chemical composition, roughness, texture, hydrophilicity and surface charge. The aim of the study was to compare the viability and adhesion strength of human gingival fibroblasts (HGFs) grown on various surfaces. Focal adhesion kinase (FAK) expression and phosphorylation in cells grown on the specimens were registered. The obtained results indicate that material type and surface processing technique have an impact on gingival fibroblast interaction with the materials.

Main publications:

Trumpaitė-Vanagienė, R., Bukelskienė, V., Aleksejunienė, J., Purienė, A., Baltriukienė, D., Rutkūnas, V. 2015. Cytotoxicity of commonly used luting cements - an in vitro study. Dental Materials Journal, vol. 34, p. 294–301.

Rutkūnas, V., Bukelskienė, V., Sabaliauskas, V., Balčiūnas, E., Malinauskas, M., Baltriukienė, D. 2015. Assessment of human gingival fibroblast interaction with dental implant abutment materials. Journal of Materials Science - Materials in Medicine, vol. 26(4), p. 1–9.

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. Action 1.1.3. Molecular processes in eukaryotic cells: the technological and medical aspects. Prof. Dr. R. Navakauskienė. 2012–2015.

Cell attachment to scaffolds and stem cell differentiation are based on either intrinsic or extrinsic signals which largely depend on the scaffold topography. The scaffolds for cell growth could be fabricated using various methods. One of the most promising methods is 3D printing. It is a process of making three dimensional solid objects from a digital file by either melting or polymerizing a material. In our study, adult stem cell signaling was studied when the cells were grown on various printed scaffolds. Results show that adult stem cell signaling responsible for cell behavior is an important factor in designing the scaffolds.

Main publication:

Iždonienė, G., Bukelskienė, V. 2015. Comparison of the biological scaffolds designed for cell growing. Veterinarija ir zootechnika, vol. 71, p. 14–20.

National Research Projects

Research Council of Lithuania. European Social Fund (ESF) under the Human Resources Development Action Programme, the Global Grant measure, project No. VP1-3.1-ŠMM-07-K-01-103. Molecular Mechanisms of Toxicity and Antitumour Activity of Quinones and Polyphenols: Enzymatic Redox Reactions and Cytotoxicity, Signal Transduction, and Proteomics. Habil. Dr. N. Čenas. 2011–2015.

Involvement of oxidative stress in 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) was shown to induce mouse hepatoma MH-22a cell death. According to our data, SAPK (SAPKs - JNK and p38 referred to as stress-activated protein kinases) expression and phosphorylation after treatment with tested quinones differed from H2O2-induced (positive reference) changes in JNK and p38 activation. Thereby, other factors may also be involved murine hepatoma cell death. The alkaline comet assay confirmed that high levels of DNA damage occurred after treatment with RH1 and MeDZQ. Consequently, oxidative stress and DNA damages both are involved in the RH1 and MeDZQ induced MH-22a cell death.

Main publications:

Nemeikaitė-Čėnienė, A., Jarašienė, R., Nivinskas, H., Šarlauskas, J., Čėnas, N. 2015. Cytotoxicity of anticancer aziridinyl-benzoquinones in murine hepatome MH22a cells: the properties of RH1-resistant subline. Chemija, vol. 26, p. 46–50.

Šarlauskas, J., Nemeikaitė-Čėnienė, A., Nivinskas, H., Miliukienė, V., Jarašienė, R., Pečiukaitytė, M., Baltriukienė, D., Bukelskienė, V., Krikštopaitis, K., Čėnas, N. 2015. Redox reactions and cytotoxicity mechanisms of anticancer aziridinyl-substituted-1,4-benzoquinones: a minireview. Chemija, vol. 26, p. 208–217.

Research Council of Lithuania. Significance of Titin Ligands Murf And C ARP In Dilated Myocardium (No. MIP-14205). Prof. Habil. Dr. V. Grabauskienė (VU Faculty of Medicine). 2014–2016.

In this work, we demonstrate that major immunogenic epitope of B19V, VP1-unique region (VP1u), hold cardiopathic potential. Echocardiographic and histological assessment of cardiac function and structure in VP1u immunized mice, revealed gradual remodelling of LV and worsening of systolic function. Observed changes are typical for DCM phenotype and follow the pattern of heart damage caused by established myosin-induced myocarditis/DCM model, used in this work as a positive reference. To our knowledge, we have created the first murine model to study B19V induced DCM.

Main publication:

Bogomolovas, J., Brohm, K., Čelutkienė, J., Balčiūnaitė, G., Bironaitė, D., Bukelskienė,V., Daunoravičus, D., Witt, Ch., Fielitz, J., Grabauskienė, V., Labeit, S. 2015. 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.

Research Council of Lithuania. Construction of Composite Bone Scaffold Material and In Vivo Evaluation of Biocompatibility and Osteopromotion (No. MIP 15552). Assoc. Prof. Dr. V. Rutkūnas (VU Faculty of Medicine, Institute of Odontology). 2015–2018.

New inorganic-organic composite materials designed for bone regeneration were produced and made ready for the study of their biocompatibility in the primary cell culture derived from dental pulp and periosteum.

Research Council of Lithuania. National Science Programme „Healthy aging“. Soft Tissue Engineering: From Cell to Artificial Tissue (No.  SEN-15049). Dr. D. Baltriukienė. 2015–2018. 

The aim of this study is to create a fragment of functional artificial tissue, based on a coculture of two different cell types on a chemically modified 3D elastomer surface. To produce a mechanically stable, biocompatible and 3D printable material, triacetoxy(vinyl)silane, vinyltrimethoxysilane and methacrylic/acrylic acid or other water- soluble monomers is used.

Research Council of Lithuania. New Generation N-Heterocyclic Quinones: Rational Synthesis and Elucidation of Anticancer Activity (No. MIP-14077).  Dr. Ž. Anusevičius. 2014–2016.

Cytotoxic activity of newly synthesized naphtho[1′,2′:4,5]imidazo[1,2-a]pyridine-5,6-diones (NPDOs) were examined against a panel of three human tumor cell lines:  adenocarcinomic alveolar basal epithelial (A-549), breast cancer (MCF-7) and promyelocytic leukemia (HL-60). According our data, NPDOs exhibited relatively high cytotoxic activity against A-549 and MCF-7 cell lines, while HL-60 cells were less sensitive to NPDOs. 3-Nitro-substituted NPDO revealed the highest potency against both A-549 and MCF-7 cell lines. Dicoumarol partly suppressed the activity of the compounds against A-594 and MCF-7 cell lines, suggesting that their cytotoxic action might be partially influenced by quinone oxidoreductase (NQO1)-mediated bioreductive activation.

Main publication:

Šarlauskas, J., Pečiukaitytė-Alksnė, M., Misevičienė, L., Marozienė, A., Polmickaitė, E., Staniulytė, Z., Čėnas, N., Anusevičius, Ž. Epub 2015 Nov.Naphtho[1′,2′:4,5]imidazo[1,2-a]pyridine-5,6-diones: Synthesis, enzymatic reduction and cytotoxic activity. Bioorganic & Medicinal Chemistry Letters (IF: 2.420), 2016 Jan, vol. 26(2), p. 512–517, doi: 10.1016/j.bmcl.2015.11.084.

Contractual Research 

To Assess Feed Additives Toxicity by Using Laboratory Mice. CC Centrinis parkas. Dr. V. Bukelskienė.

Evaluation of the Biocompatibility of Scaffolds Designed for Bone Formation. CC Audronės 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.

Study of Cell Interaction with the Hydrogel Samples. CC Ferentis. 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)
Vilnius Gediminas Technical University, Faculty of Fundamental Sciences, Department of Chemistry and Bioengineering (Lithuania)
CC Thermo Fisher Scientific Baltics
CC Audronės odontologijos gydykla
CC Melt Water
CC Prodentum
CC Centrinis parkas
CC Ferentis 

OTHER SCIENTIFIC ACTIVITIES

Dr. D. Baltriukienė –

Dr. V. Bukelskienė –

 

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 fellow: Dr. R. Jančienė.
Research fellows: Dr. A. Klimavičius, Dr. Z. Staniulytė, Dr. L. Kosychova.
Junior research fellow: Dr. R. Sirutkaitis.
Assistants: J. Meškauskas, D. Podėnienė, R. Rozenbergas, S. Palaikienė.

RESEARCH INTERESTS

Synthesis of heterocyclic, amino acid and polyether derivatives

RESEARCH PROJECTS CARRIED OUT IN 2015

Project 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. 2014–2016. 

Search for the synthesis methods of imidazo[1,5-a][1,5]benzodiazepine derivatives.

Interaction of model tetraethyleneglycol (TEG) with 1,3-propanesultone and bromomethylbiphenyl was investigated. Optimal reaction conditions were established in various volumes and corresponding di-substituted TEG derivatives were synthesized. TEG reaction with variously substituted phenols (o-isopropyl, p-tert-butyl and similar) was further investigated with the aim to create synthesis methods for highly pure TEG diphenylethers.

Reaction of 5-benzyl-1,5-benzodiazepin-2-ones with diethylmalonate and ethylisocyanoacetate was performed under Wittig–Horner reaction conditions using diphenyl (or diethyl)chlorophosphate. It was found that the reaction with diethylmalonate did not occur under these conditions. Tricyclic ethyl-6-benzyl-5,6-dihydro-4H-imidazo[1,5-a][1,5]benzodiazepin-3-carboxylates were afforded in the reaction with ethylisocyanoacetate.

Main publications:

Janciene, R., Javorskis, T., Mikulskiene, G., Vektariene, A., Vektaris, G., Klimavicius, K. A. 2015. Novel synthesis of quinazolino[3,2-a][1,5]benzodiazepines: an experimental and computational study. ARKIVOC, vol. 2015, issue 5, p. 366–382, doi: http://dx.doi.org/10.3998/ark.5550190.p009.141.

Kosychova, L., Karalius, A., Staniulytė, Z., Sirutkaitis, R. A., Palaima, A., Laurynėnas, A., Anusevičius, Ž. 2015. New 1-(3-nitrophenyl)-5,6-dihydro-4H-[1,2,4]triazolo[4,3- a][1,5]benzodiazepines: synthesis and computational study. Molecules, vol. 20, no. 4, p. 5392–5408.

Alesenkov, A., Pilipavičius, J., Beganskienė, A., Sirutkaitis, R., Sirutkaitis, V. 2015. Nonlinear properties of silver nanoparticles explored by a femtosecond Z-scan technique. Lithuanian Journal of Physics, vol. 55, no. 2, p. 100–109.

National Research Projects

Agency for Science, Innovation and Technology. National program to support R&D contracts, invitation No. US1501. Research in Development of New Methods for Making Aromatic Ethers of Polyethylene Glycols.

Study of the Synthesis of Aromatic and Cyclohexane Carboxylic Acid Derivatives. Study of the Synthesis and Purification of Cis- and Trans-4-Amino-Cyclohexanecarboxylic Acid Derivatives. Study of the Synthesis of Indole Derivatives Containing Amidine Group. Dr. R. Jančienė 2015.

Methods of synthesis of target organic compounds were developed, reaction conditions of separate steps were optimized, developed technology was applied for the preparative synthesis and the experimental batches were prepared under R&D contracts.

Contractual Research

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

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

Investigation of Cyclization of P-Cyano-O-Nitrobenzyl-P-Cyanophenylketone and Synthesis of Experimental Batches of DAPI Dihydrochloride. Contract with CC Elymus. Dr. R. Jančienė.

Research in Development of New Methods for Making Aromatic Ethers of Polyethylene. Contract with Ramidus AB (Sweden). Dr. R. Jančienė.

Study of the Synthesis and Purification of Cis- and Trans-4-Aminocyclohexane Carboxylic Acid Derivatives. Contract with Bapeks Sia (Latvia). Dr. R. Jančienė.

Synthesis of Sulfur Heterocyclic Derivatives and Cyclic Polyether Derivatives. Contract with Synthon Chemicals GmbH (Germany). Dr. R. Jančienė.

Development of Viable Methods for The Synthesis of Various Organic Compounds and Preparation of their Experimental Batches. Contract with Synthon Chemicals GmbH (Germany). Dr. R. Jančienė.

Synthesis of N-Phenyl-Ethylenediamine Methacrylamide. Contract with D+T Microelectronica, AIE (Spain). Dr. R. Jančienė.

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

Centre of Physical Sciences and Technology (Lithuania)
CC Thermo Fisher Scientific Baltics (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 fellow: Prof. Dr. R. Navakauskienė.
Senior research fellow: Dr. A. Kalvelytė.
Research fellows: Dr. V. V. Borutinskaitė, Dr. A. Imbrasaitė, Dr. J. Savickienė, Dr. G. Treigytė.
Junior research fellows: Dr. N. Krestnikova, A. Stulpinas, A. Zentelytė.
Doctoral students: S. Baronaitė, M. Glemžaitė, G. Valiulienė, A. Virkšaitė.

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 2015

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.

We have analyzed epigenetic chromatin modifications in mesenchymal stem cells (MSCs) from human amniotic fluid sharing embryonic and adult stem cells characteristics of normal pregnancy and polyhydroamniotic fluid with fetus abnormalities. We have shown the differences in the expression of chromatin modifiers (DNMT1, HDAC1/2), euchromatic activating (H4ac, H4K16ac) histone marks dependently on cell morphologic, growth characteristics and differentiation level.

In the context of applications of histone H2AX in the treatment and diagnosis of cancer, the kinetics of histone H2AX phosphorylation, a marker for DNA damage, was studied. Increase of gamma-H2AX phosphorylation at Ser139 was registered in lung cancer cells in the later times of treatment with different cytotoxic chemicals and DNA-damaging therapeutic agents (cisplatin, RH-1, H202, duroquinone, quercetin).

Main publications:

Borutinskaitė, V., Navakauskienė, R. 2015. The histone deacetylase inhibitor BML-210 influences gene and protein expression in human promyelocytic leukemia NB4 cells via epigenetic reprogramming. International Journal of Molecular Sciences, vol. 16(8), p. 18252–69, doi: 10.3390/ijms160818252.

Krestnikova, N., Stulpinas, A., Imbrasaite, A., Sinkeviciute, G., Kalvelyte, A.V. 2015. JNK implication in adipocyte-like cell death induced by chemotherapeutic drug cisplatin. J Toxicol Sci., vol. 40(1), p. 21–32.

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. Action 1.1.3. Molecular Processes in Eukaryotic Cells: the Technological and Medical Aspects. Prof. Dr. R. Navakauskienė. 2012–2015.

The aim of the project is to define healthy and cancerous cells, to investigate molecular mechanisms of cell proliferation and apoptosis, to identify diagnostic, predictive and prognostic biomarkers for developing new application protocols. In the present study we have used chemical agents that affect cancer cell functioning and chromatin remodeling. We compared healthy, untreated and treated tumor cells and performed transcriptomic and proteomic analysis; studied stem cell interactions with the substrate induced intracellular processes. Molecular mechanisms of anoikis regulation may serve as a target both in reducing metastatic cancer growth and in increasing cell therapy efficiency. Studies of kinase AKT and MAP kinases (ERK, p38 and JNK) involvement in anoikis-regulation revealed differences in dependence of kinase phosphorylation on cell-cell/ cell-substrate contacts in cancer and stem cells. Results contribute to new possibilities in regenerative medicine and cancer therapy.

National Research Projects

Research Council of Lithuania. European Social Fund (ESF) under the Human Resources Development Action Programme, the Global Grant measure, project No. VP1-3.1-ŠMM-07-K-01-103. Molecular Mechanisms of Toxicity and Antitumour Activity of Quinones and Polyphenols: Enzymatic Redox Reactions and Cytotoxicity, Signal Transduction, and Proteomics. Habil. Dr. N. Čenas. 2011–2015.

In 2015 we showed that different mode of activation and the involvement of MAPKs in apoptosis triggered by different oxidative stress-inducing agents were shown in A549 lung cancer cell line. 

Research Council of Lithuania. The Role of Molecular Modulators in the Hematological System during Cell Senescence, Differentiation and Regeneration (No. SEN-12/2015) Prof. R. Navakauskienė. 2015–2018.

The cells of hematopoietic system are the precursors of hematopoietic stem cells, those the main characteristics are ‐ renewal and differentiation into different blood cells. Aging of the hematological system is associated with age‐dependent hematological malignancies. We investigate the molecular factors and their role in human hematopoietic system and leukemia cell differentiation, regeneration and aging processes.

Research Council of Lithuania. Regulation of Amniotic Fluid‐Derived Stem Cell Functioning by Microrna and Epigenetic Factors (No. MIP-57/2015) Dr. J. Savickienė. 2015–2018.

Amniotic fluid‐derived stem cells endowed with self‐renewal and pluripotent differentiation capacities are suitable for cell therapy in regenerative medicine and are not tumorigenic and do not raise ethical problems. We investigate the regulatory role of epigenetic factors in the determination of amniotic stem cell fate – the potential of the growth and differentiation into specialized cell types and death.

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

The aim of the project is to determine amniotic fluid cytological, molecular and epigenetic differences that characteristic for normal and pathological pregnancies. We identified amniotic fluid proteins characteristic pathological pregnancies and demonstrated that epigenetic studies are important to identify epigenetic biomarkers and regulatory mechanisms for clarification of physiological and pathological development of the fetus.

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

Different types of pollen are characterized by specific content of proteins. During the project, a comprehensive comparative analysis of proteomes typical to different kinds of clover - 'Meduna' white, 'Faraon' Egyptian, ‘Kiršiniai’ and ‘Vyčiai’ red clover, and dandelion Taraxacum officinale was performed. 

Main publications:

Savickiene, J., Treigyte, G., Baronaite, S., Valiuliene, G., Kaupinis, A., Valius, M., Arlauskiene, A., Navakauskiene, R. 2015. Human amniotic fluid mesenchymal stem cells from second- and third-trimester amniocentesis: differentiation potential, molecular signature, and proteome analysis. Stem Cells International, 2015:319238, doi: 10.1155/2015/319238.

Valiuliene, G., Stirblyte, I., Cicenaite, D.,   Kaupinis, A., Valius, M., Navakauskiene, R.  2015. Belinostat, a potent HDACi, exerts antileukemic effect in human acute promyelocytic leukemia cells via chromatin remodelling. Journal of Cellular and Molecular Medicine, vol. 19(7), p. 1742–55, doi: 10.1111/jcmm.12550.

International Research Projects

COST Action CM1106: Chemical Approaches to Targeting Drug Resistance in Cancer Stem Cells (Stemchem). Prof. R. Navakauskienė. 2012–2016.

The COST Action CM1106 aims at uniting researchers with expertise in drug design, medicinal chemistry of synthetic and natural compounds and biomedical investigators. Researchers of the Department of Molecular Cell Biology in collaboration with Nice University (France) and Milano University (Italy) studied the effects of newly synthesized agents on epigenetic changes in cancer and cancer stem cells after treatment. Some of tested novel compounds showed effects on histone demethylation in cancer cells. These compounds could become drug candidates that target cancer and cancer stem cells.

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

Linkoping University (Sweden)
Nice University (France)
Milan University (Italy)
Malta University (Malta)
Northwestern University (USA) 

OTHER SCIENTIFIC ACTIVITIES

Prof. R. Navakauskienė –

  • member of American Society for Cell Biology;
  • member of Lithuanian Stem Cell Researchers Association;
  • member of Federation of European Biochemical Society.

Dr. A. V. Kalvelytė –

  • member of Lithuanian Stem Cell Researchers Association;
  • member of Federation of European Biochemical Society.

Dr. V. Borutinskaitė –

  • member of Lithuanian Stem Cell Researchers Association;
  • member of Federation of European Biochemical Society.

Dr. A.  Imbrasaitė –

  • member of Federation of European Biochemical Society.

Dr. N. Krestnikova –

  • member of Federation of European Biochemical Society.

A. Stulpinas –

  • member of Lithuanian Stem Cell Researchers Association;
  • member of Federation of European Biochemical Society.

 

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. 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, Dr. J. Stankevičiūtė.
Junior research fellows: R. Meškienė, Dr. S. Povilionienė, Dr. R. Stanislauskienė, Dr. S. Kutanovas, J. Vaitekūnas.
Doctoral students: A. Aučynaitė, J. Jakubovska, V. Petkevičius, M. Sadauskas, E. Šimoliūnas, N. Urbelienė. 

RESEARCH INTERESTS

Molecular biology and genetics of bacteria and bacteriophages

Genetic and biochemical diversity of microorganisms, enzyme biotechnology

RESEARCH PROJECTS CARRIED OUT IN 2014

Project Supported by University Budget

Investigation of Genetic and Biochemical Diversity of Bacteriophages and Microorganisms Dr. R. Meškys. 2014–2018.

Several biocatalytic processes based on laccases have been developed for degradation of bisphenol, and bioelectrocatalytic conversions. Nanostructures based on the recombinant mutant of alpha-synuclein have been developed.

A novel virus vB_ArtM-ArV1 (ArV1) was isolated from soil using Arthrobacter sp. 68b strain for phage propagation. Transmission electron microscopy showed its resemblance to members of the family Myoviridae: ArV1 has an isometric head (~74 nm in diameter) and contractible nonflexible tail (~192 nm). Whole-genome sequencing of ArV1 revealed a linear circularly permutated double-stranded DNA (71,200 bp) with a G+C content of 61.6 %. In total, the genome contains 101 ORFs yet encodes no tRNA genes. The data presented will help advance our understanding of genetic diversity and evolution within phages from the order Caudovirales.

Main publications:

Ivanec-Goranina, R., Kulys, J., Bachmatova, I., Marcinkevičienė, L., Meškys, R. 2015. Laccase-catalyzed bisphenol a oxidation in presence of 10-propyl sulfonic acid phenoxazine. J. Environ. Sci., vol. 30, p. 135–139, doi: 10.1016/j.jes.2014.07.026.

Povilonienė, S., Časaitė, V., Bukauskas, V., Šetkus, A., Staniulis, J., Meškys, R. 2015. Functionalization of a-synuclein fibrils. Beilstein J. Nanotech., vol. 6, p. 124–133.

Kaliniene, L., Zajančkauskaitė, A., Šimoliūnas, E., Truncaitė, L., Meškys, R. 2015. Low-temperature bacterial viruses VR – a small but diverse group of E. coli phages. Arch. Virol., vol. 160, p.1367–1370, doi: 10.1007/s00705-015-2388-0.

National Research Projects

Research Council of Lithuania. 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.

The CHORD project aimed at the screening and construction of novel oxidoreductases, applicable for the region-selective hydroxylation of the pyridine ring and the synthesis of the chemical analogs of the nucleosides and nucleotides. Novel pyridines-specific hydroxylating mono- and dioxygenases as well as mono- and dioxygenases with the novel substrate specificity, e.g. hydroxylating pyridine derivatives with multiple side groups have been screened and applied for synthesis of various pyridones and pyridin-2-amines. The synthesis of novel acyclic and cyclic pyridone-based nucleosides and nucleotides was carried out. In total, 7 nucleosides and 4 nucleotides were synthesized. None of the tested nucleosides showed inhibitory properties against Klenow exo- polymerase as well as M.MuLV and HIV-1 reverse transcriptases. The nucleotides containing 4-chloro- and 4-bromo-2-pyridone as a nucleobase were accepted by the Klenow fragment, yet at the expence of fidelity and extension efficiency.

Main publications:

Tauraitė, D., Dabužinskaitė, J., Ražanas, R., Urbonavičius, J., Stankevičiūtė, J., Serva, S., Meškys, R. 2015. Synthesis of novel derivatives of 5-carboxyuracil. Chemija, vol.  26, p. 120–125.

Stankevičiūtė, J., Kutanovas, S., Rutkienė, R., Ražanas, R., Tauraitė, D., Striela, R., Meškys, R.  2015. Ketoreductase TpdE from Rhodococcus jostii TMP1: characterization and application in the synthesis of chiral alcohols. PeerJ  3:e1387, https://dx.doi.org/10.7717/peerj.1387.

Research Council of Lithuania. Novel prodrug activation systems for cancer genotherapy (SEN-15027) Dr. J. Urbonavičius. 2015–2018.

Aim of the project is to develop novel prodrugs and their activating enzymes applicable for cancer therapy.

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

The aim of this project is to investigate the initial steps of phage lytic infection by using proteogenomic approaches. For this, three E. coli-specific bacteriophages, namely T4, FV3 and VpaE1, belonging to different genera (T4-like, rV5-like and Felix 01-like viruses) have been chosen. Morphological and physiological characteristics as well as genomic and proteomic features of FV3 have been published previously. During this project, the genome sequence of VpaE1 has been determined and deposited in GenBank under accession number (KM657822).

Main publication:

Šimoliūnas, E., Vilkaitytė, M., Kaliniene, L., Zajančkauskaitė, A., Kaupinis, A., Staniulis, J., Valius, M., Meškys, R., Truncaitė, L. 2015. Incomplete LPS core-specific Felix01likevirus vB_EcoM_VpaE1. Viruses-Basel, vol.  7(12), p. 6163–6181, doi:10.3390/v7122932.

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.

In this project (INMARE), Vilnius University will be represented by the scientists from the Department of Molecular Microbiology and Biotechnology (Institute of Biochemistry), headed by Dr. Rolandas Meškys, whose main focus will be the development of the innovative enzyme-screening techniques, involving the construction of tailored microorganisms and the synthesis of smart substrates.

The companies involved in the project, such as Bayer, Novozymes and others, are market leaders in enzyme production as well as biocatalysis, and aim to deliver safer (pharmaceuticals), cheaper (agriculture) and biobased (biopolymers) products. In addition, all participating companies feel responsible and committed to render chemical processes greener. Other industrial partners have impressive track records in discovery of natural products for biomedical purposes, especially anti-cancer therapy (PharmaMar), environmental clean-up applications (INOFEA) and biocatalysis for the fine chemicals (evocatal GmbH).

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. Ž. Anusevičius, Dr. K. Krikštopaitis, Dr. J. Šarlauskas.
Research fellows: Dr. A. Marozienė, Dr. G. Mikulskienė, Dr. V. Miliukienė, Dr. L. Misevičienė. 
Doctoral students: E. Polmickaitė, B. Valiauga.

RESEARCH INTERESTS 

Investigations of the molecular mechanisms of the antitumour activity and cytotoxicity of aziridinyl-substituted and –unsubstituted quinones, in particular the impact of their redox activity on their cytotoxic action

Investigations of the molecular mechanisms of cytotoxicity of novel nitroaromatic and related compounds, in particular the impact of their redox activity and electronic properties on their cytotoxic action

The studies of the catalytic mechanism of mamalian and bacterial quinone- and nitroreductases

The studies of redox reactions of flavo-heme proteins, possibly participating in the bioreductive activation of quinoidal and nitroaromatic compounds

The studies of mechanisms of cytotoxicity of natural and synthetic polyphenolic antioxidants

RESEARCH PROJECTS CARRIED OUT IN 2015

Project Supported by University Budget

Molecular Mechanisms of Enzymatic Activation, Detoxification, Biodegradation, and Cytotoxicity of Redox Active Xenobiotics. Habil. Dr. N. Čėnas. 2011–2016.

The catalytic scheme of single-electron reduction of quinones and nitroaromatic compounds by flavohemoglobin of S. aureus has been elucidated including the use of the ‚stopped-flow‘ experiments. It shows that 2-OH-1,4-naphthoquinones display an enhanced reactivity towards this enzyme, which opens the new perspectives for the creation of new antibacterial drugs of this group. It was shown that T. maritima thioredoxin reductase catalyzed the mixed single-and two-electron reduction of quinones and nitroaromatic compounds via FAD cofactor, whose general substrate specificity is opposite to that of S. aureus flavohemoglobin.

Main publication:

Valiauga, B., Rouhier, N., Jacquot, J.-P., Čėnas, N. 2015. Quinone- and nitroreductase reactions of Thermotoga maritima thioredoxin reductase. Acta Biochim. Polon., vol. 62, p. 303–309. 

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. 2014–2016.

Main results of 2015 were as follows: 8 new compounds of this group were synthesized; their single-and two-electron redox properties in reactions with cytochrome P-450 reductase and DT-diaphorase were determined, and their cytotoxicity in 3 mammalian tumour cell lines was investigated.

Research Council of Lithuania. European Social Fund (ESF) under the Human Resources Development Action Programme, the Global Grant measure, project No. VP1-3.1-ŠMM-07-K-01-103. Molecular Mechanisms of Toxicity and Antitumour Activity of Quinones and Polyphenols: Enzymatic Redox Reactions, Cytotoxicity, Signal Transduction and Proteomics. Habil. Dr. N. Čenas. 2011–2015.

The structure-activity relationships in the toxic action of quinones towards murine hepatoma MH22a cells were elucidated, the systematically increased activity of aziridinyl-substituted benzoquinones has been demonstrated. Two MH22a resistant to a novel aziridinyl-benzoquinone antitumour agent RH1 were obtained, the changes in their enzymatic activities elucidated, showing unaltered balance of antioxidant/prooxidant enzymes, and a markedly decreased expression of NAD(P)H:quinone oxidoreductase and glutathione-S-transferase. 

Main publications: 

Nemeikaitė-Čėnienė, A., Jarašienė, R., Nivinskas, H., Šarlauskas, J., Čėnas, N. 2015. Cytotoxicity of antitumour aziridinyl-benzoquinones in murine hepatoma MH22a cells: the properties of RH1-resistant subline. Chemija, vol. 26, p. 46–50.

Šarlauskas, J., Nemeikaitė-Čėnienė, A., Nivinskas, H., Miliukienė, V., Jarašienė, R., Pečiukaitytė, M., Baltriukienė, D., Bukelskienė, V., Krikštopaitis, K., Čėnas, N. 2015. Chemija, vol. 26, p. 208–217.

International Research Projects

COST Action CM1307 Targeted Chemotherapy Towards Diseases Caused by Endoparasites. Dr. J. Šarlauskas, Habil. Dr. N.  Čėnas. 2014–2017.

Main results: synthesis of 6 nitroheterocyclic compounds, testing of their antileishmanial and antiplasmodial activity.

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. 2014–2015.

Quinone reductase activities of flavocytochrome b2 from Hansenula polymorpha were elucidated, showing an increase of reaction rate upon increase in the reduction potential of quinone. The Au-nanoparticle-mediated flavocytochrome b2-electrode electron transfer has been investigated for the construction of new biosensors for L-lactate. 

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

Universite de Paris Sud, Orsay (France)
Universite de Lorraine, Nancy (France)
Victoria University of Wellington (New Zealand)
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 

Senior research fellow: Dr. M. Valius.
Research fellow: Dr. A. Kaupinis.
Junior research fellow: Dr. M. Ger.
Doctoral students: A. Androšiūnaitė, D. Kučiauskas, N. Šumilova. 

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

Biomarkers for cancer diagnostics and treatment

RESEARCH PROJECTS CARRIED OUT IN 2015

Project Supported by University Budget

New Technologies for Tumor Diagnosis and Treatment Based on Nano-Materials and Proteomics. Dr. M. Valius. 2014–2018.

During the implementation of this project we have generated drug-resistant breast cancer cell lines and used them for performing high throughput label-free quantitative proteomic analysis to find proteins that might be served as drug-resistance drug protein markers. More than 4000 proteins were identified and quantified; bioinformatic analysis allowed to categorize more than 30 proteins as potential biomarkers. In parallel, proteomic analysis of cell surface proteins revealed ~20 proteins that might be used to visualize breast cancer cells and cells resistant to chemotherapy in future. 

Main publications:

Valiuliene, G., Striblyte, I., Cicenaite, D., Kaupinis, A., Valius, M., Navakauskiene, R. 2015.  Belinostat, a potent HDACi, exerts antileukaemic effect in human acute promyelocytic leukaemia cells via chromatin remodeling. J. Cell. Mol. Med., vol 19, no 7, p. 1742–1755, doi: 10.1111/jcmm.12550.

Šimoliūnas, E., Vilkaitytė, M., Kaliniene, L., Zajančkauskaitė, A., Kaupinis, A., Staniulis, J., Valius, M., Meškys, R., Truncaitė, L. 2015. Incomplete LPS Core-Specific Felix01-Like Virus vB_EcoM_VpaE1. Viruses, vol. 7(12), p. 6163–6181, doi:10.3390/v7122932.

National Research Projects

Research Council of Lithuania: High Throughput Proteomics for Cancer Cell Surface Protein Recognition by Quantum Dots (No. MIP-033/2014) Dr. M. Valius, 2014–2016.

The aim 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. To this end we have generated a number of cell lines resistant to the novel anticancer drug RH1 and performed global differential high throughput proteomics analysis, cytoplasmic membrane proteome and search for active kinases by the novel multiplex kinase inhibitor beads assay. Bioinformatic analysis of this high content date allowed identifying a number of possible mechanisms of cell resistant to the RH1 drug.

aGer, M., Kaupinis, A., Nemeikaite-Ceniene, A., Sarlauskas, J., Cicenas, J., Cenas, N., Valius, M. 2015. Quantitative proteomic analysis of anticancer drug RH1 resistance in liver carcinoma. Biochim Biophys Acta, vol. 1864(2), p. 219–232.

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.  J. Biomed. Nanotechnol. Vol. 11, p. 841–853, doi: http://dx.doi.org/10.1166/jbn.2015.2007

Cicenas, J., Kalyan, K., Sorokinas, A., Stankunas, E., Levy, J., Meskinyte, I., Stankevicius, V., Kaupinis, A., Valius, M. 2015. Roscovitine in cancer and other diseases. Ann Transl Med., vol. 3(10), p.135, doi: 10.3978/j.issn.2305-5839.2015.03.61.

Research Council of Lithuania: Novel Biomarkers for Individualized Therapy of Colon Cancer: Proteomics, Micrornomics and Clinics (No. SEN-17/2015 ILSS-150000-2330) Project manager Prof. A. Laurinavicius, work package manager Dr. M. Valius. 2015–2018.

In this project we will use chemotherapy‐sensitive and ‐resistant CRC cell lines that will be established or have been established already. We will perform highthroughput quantitative proteomic and microRNomic analysis of the cell lines. Potential predictive biomarkers will be identified from the bioinformatic analysis of proteomic and microRNomic data and validated in various models of cell culture. Next, the selected set of potential protein and microRNA biomarkers will be validated in human CRC clinical samples.

The project will result in the discovery of potential predictive biomarkers for the successful personalized CRC adjuvant chemotherapy.

Contractual Research

Mitochondria Proteome (New Technology: High Throughput Quantitative Proteomics. Institute for Biomedical Research. Lithuanian University of Health Sciences.

Study of Apple Proteome. Institute of Horticulture, Lithuanian Research Centre for Agriculture and Forestry Plant biology.

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

Swiss Institute of Bioinformatics, Geneva (Switzerland)
Aargus University, Aargus (Denmark)
Schepens Eye Research  Institute, Harvard Medical School, Boston (USA)
University of North Carolina School of Medicine, Department of Farmacology, Chapel Hill (USA)
Lithuania National Cancer Center, Vilnius (Lithuania)

OTHER SCIENTIFIC ACTIVITIES

Dr. M. Valius –

  • editorial board member of the journal MAP Kinases.