Institute of Biochemistry

Department of Bioelectrochemistry and Biospectroscopy

Head dr. Gintaras Valinčius
Phone: +37052234435
email:

Formation of plasma membrane is considered as a crucial event during evolution and life, as known today, would not be possible without them. Actual plasma membranes contain a complex, heterogeneous distribution of lipids and membrane proteins which interact to create important biological functions. To investigate this complex membrane environment significant progress has been made to model native membranes.

Our research group focuses on development of nature inspired models, in particular, surface tethered phospholipid membranes (tBLM) and membrane-protein complexes exhibiting catalytic activities. The group addresses problems related to basic life-science as well as applications in biomedicine.  In particular, including sensor development for various endogenous and exogenous pathogens and ultrasensitive detection of microbial toxins (α-hemolysin (αHL), Vaginolysin (VLY), Pneumolysin (PLY), etc.).

We offer a broad spectrum of technological solutions to reconstitute proteins into the tethered bilayer for structural and functional studies. Bioelectrochemical and Biospectroscopic techniques and relevant expertise can be accessed by the external users through the standard open access procedures implemented at Vilnius University. We seek both academic and industrial partnerships to further develop molecular devices based on tethered bilayer technologies and advance basic knowledge in the field of the protein function in biological membranes.  In particular, we seek to establish partnerships with theoretical groups having expertise in modelling structures of biomolecules in membranes as well as predicting the dynamic properties of ion carriers in confined nano-compartments. Also, we aim to spread our technological knowledge into the areas of biochemistry and molecular biology where the phospholipid milieu is required for functional reconstitution of membrane proteins for structural and functional studies. Joint initiatives for EU and other international funding for research and technology development are also sought-after.

Our resources contain proprietary technology and compounds for the production of the self-assembled molecular anchors and tethered phospholipid bilayers. Wide spectrum of electrochemical and spectroscopy instrumentation for molecular level characterization of the structure and function of phospholipid bilayers, membrane-protein interaction, detection of membrane-damaging toxins and surface visualization by the fluorescence and atomic force microscopies. Proprietary algorithms and software for the analysis of the electrochemical impedance response of tethered bilayers.

Main Grants (2007–2017):

1. Research council of Lithuania grant "Advanced Technology Development Program" project, B-38, AMILOIDE. (2008-2010). Project partners: LSMU Institute of Biomedical science, LSMU Neurological clinic, Institute of Biotechnology, Institute of Chemistry, Institute of Physics. (Project leader dr. G. Valinčius).
2. Research council of Lithuania grant MIP project, MIP-11395, IMFABITE (2011-2012). Immobilized phospholipid bilayers for protein reconstitution. (Project leader dr. G. Valinčius).
3. Research council of Lithuania grant National research programme "Chronic Non-Infectious Diseases" project, LIG-12048, MALPALMA (2012-2014) (Project leader: dr. R. Morkūnienė).
4. MINIFOB funded by European Social Fund Agency, “Miniaturized phospholipid biosensors” (2013-2015), (Principal investigator: dr. G. Valinčius).
5. Biosentox (2017-2019) “Biosensors for toxin detection” funded by VU and Lithuanian business support agency (Principal investigation – G. Valinčius).

 Main Publications (2007–2019):

Dagys M., A. Laurynėnas, D. Ratautas J. Kulys, R. Vidžiūnaitė, M. Talaikis, G. Niaura, L. Marcinkevičienė, R. Meškys, Shleev. 2017. Oxygen electroreduction catalysed by laccase wired to gold nanoparticle via trinuclear copper cluster. Energy&Environmental Science 10: 498-502

Preta G. Understanding the Dr. Jekyll and Mr. Hyde nature of apoptosis-inducing factor: future perspectives. Biomedical Journal 40: 239-240;

Penkauskas T, Preta G. (2019): Biological applications of tethered bilayer lipid membranes. Biochimie. Nov 22;157:131-14

Santos A.L.,  Preta G. (2018): Lipids in the cell: organization regulates function. Cell Mol Life Sci.. Jun;75(11):1909-1927.

Griffin S, Preta G., Sheldon IM. (2017): Inhibiting mevalonate pathway enzymes increases stromal cell resilience to a cholesterol-dependent cytolysin. Sci. Rep. Dec 6;7(1):17050.

Valiuniene, T.Petrulioniene, I.Baleviciutei, L.Mikoliunaite, G.Valincius. Formation of hybrid bilayers on silanized thin-film Ti electrode. Chemistry and Physics of Lipids. 2017,  202, 62-68.

Ragaliauskas T., M. Mickevičius, B. Rakovska, T. Penkauskas,J. Vanderah, F.Heinrich,G. Valinčius. 2017. Fast formation of low-defect-density tethered bilayers by fusion of multilamellar vesicles. Biochimica et Biophysica Acta (BBA) - Biomembranes 1859: 669-678.

Eicher-Lorka O., T. Charkova, A. Matijoska, Z. Kuodis, G. Urbelis, T. Penkauskas, M. Mickevičius, A. Bulovas, G. Valinčius. 2016. Cholesterol-based tethers and markers for model membranes investigation. Chemistry and Physics of Lipids 195: 71-86.

Preta G., M. Jankunec, F. Heinrich, S. Griffin, I.M. Sheldon, G. Valinčius. 2016. Tethered bilayer membranes as a complementary tool for functional and structural studies: The pyolysin case. Biochimica et Biophysica Acta-Biomembranes 1858: 2070-2080.

Talaikis M., O. Eicher-Lorka, G. Valinčius, G. Niaura. 2016. Water-Induced Structural Changes in the Membrane-Anchoring Monolayers Revealed by Isotope-Edited SERS. Journal of Physical Chemistry C 120: 22489-22499

Valinčius G., M. Mickevičius, T. Penkauskas, M. Jankunec. 2016. Electrochemical Impedance Spectroscopy of Tethered Bilayer Membranes: An Effect of Heterogeneous Distribution of Defects in Membranes. Electrochimica Acta 222: 904-913.

Rakovska B., T. Ragaliauskas, M. Mickevičius, M. Jankunec, G. Niaura, D.J. Vanderah, G. Valinčius. 2015. Structure and function of the membrane anchoring self-assembled monolayers. Langmuir 31: 846-857.

Ragaliauskas T., M. Mickevičius, R. Budvytytė, G. Niaura, B. Carbonnier, G. Valinčius. 2014. Adsorption of b-amyloid oligomers on octadecanethiol monolayers. Journal of Colloid and Interface Science 425: 159-167.

Budvytytė R., M. Mickevičius, D.J. Vanderah, F. Heinrich, G. Valinčius. 2013. Modification of tethered bilayers by phospholipid exchange with vesicles. Langmuir 29: 4320-4327.

Budvytytė R., M. Plečkaitytė, A. Žvirblienė, D. J. Vanderah, G. Valinčius. 2013. Reconstitution of cholesterol-dependent vaginolysin into tethered phospholipid bilayers: implications for bioanalysis. PLOS ONE. 8: e82536.

Budvytytė R., G. Valinčius, G. Niaura, V. Voiciuk, M. Mickevičius, H. Chapman, H.Z. Goh, P. Shekhar, F. Heinrich, S. Shenoy, M. Losche, D.J. Vanderah. 2013. Structure and properties of tethered bilayer lipid membranes with unsaturated anchor molecules. Langmuir 29: 8645-8656.

Valincius G., T. Meskauskas, F. Ivanauskas. 2012. Electrochemical impedance spectroscopy of tethered bilayer membranes. Langmuir 28: 977-990.

Voiciuk V., G. Valincius, R. Budvytyte, A. Matijoska, I. Matulaitiene, G. Niaura. 2012. Surface-enhanced Raman spectroscopy for detection of toxic amyloid beta oligomers adsorbed on self-assembled monolayers. Spectrochimica Acta Part A-molecular and Biomolecular Spectroscopy 95: 526-532.

Cizas P., R. Budvytyte, R. Morkuniene, R. Moldovan, M. Broccio, M. Loesche, G. Niaura, G. Valincius, V. Borutaite. 2010. Size-dependent neurotoxicity of beta-amyloid oligomers Archives of Biochemistry and Biophysics 496:84-92.

K. J. Kwak, G. Valincius, W.-C. Liao, X. Hu, X. Wen, A. Lee, B. Yu, D. J. Vanderah, W. Lu and L. J. Lee. 2010. Formation and finite element analysis of tethered bilayer lipid structures. Langmuir 26:18199-18208.

McGillivray D., G. Valincius, F. Heinrich, J. Robertson, D. Vanderah, W. Febo-Ayala, I. Ignatjev, M. Lösche, J. Kasianowicz. 2009. Structure of functional Staphylococcus aureus alpha-hemolysin channels in tethered bilayer lipid membranes. Biophysical Journal 96: 1547-1553.

Kazakevičienė, B., G. Valinčius, M. Kažemėkaitė, V. Razumas. 2008. Self-assembled redox system for bioelectrocatalytic assay of L-ascorbylphosphate and alkaline phosphatase activity. Electroanalysis 20: 2235-2240.

Valincius, G., F. Heinrich, R. Budvytyte, D.J. Vanderah, Y. Sokolov, J.E. Hall, M. Loesche. 2008. Soluble amyloid ß oligomers affect dielectric membrane properties by bilayer insertion and domain formation: Implications for cell toxicity. Biophysical Journal 95: 4845-4861.

McGillivray, D. J., G. Valinčius, D. J. Vanderah, W. Febo-Ayala, J. T. Woodward, F. Heinrich, J. Kasianowicz, M. Losche. 2007. Molecular-scale structural and functional characterization of sparsely tethered bilayer membranes. Biointerphases 2: 21-33

Collaborations:

Long-term projects with research groups at the Institute for Biotechnology and Bioscience Research at the University of Maryland (College Park, USA), Carnegie Mellon University (USA) and NIST Center for Neutron Research (USA), Niels Bohr Institute at University of Copenhagen (Denmark).

Swansea University, Wales, UK: biological and biophysical approaches for the characterization of the cholesterol-dependent cytolysins Pyolysin (PLO).

Haifa University, Israel: using biophysical approaches (EIS and AFM) to study the structure and function of the pro-apoptotic protein BAX.

Malmö University, Sweden: prof. Johan Engblom. Dermal Drug Delivery - Increasing bioavailability in viable skin.

Department of Biological Models

Head dr. Virginija Bukelskienė
phone: +370 5 223 4408
email:

The Department of Biological Models focuses on the study of adult stem cells and their application for regenerative medicine using two model systems - in vitro (cell cultures) and in vivo (experimental animals). The team has deep knowledge of artificial tissue construction, using polymer scaffolds. Their expertise includes the evaluation of material biocompatibility, cell-surface interactions and methods of stem cell differentiation and associated processes assessment. The ultimate goal of these studies is to control the behavior of stem cells, directing them towards specific lineage differentiation by tailoring the chemical composition, physical properties and surface coating of the materials. Fabricated segments of artificial tissues are tested in vivo – by surgical implantation in animals.

The department has a modern laboratory for experimental animals, which is designed for work with mice, rats and rabbits. The animals are kept either in conventional or SPF (specific-pathogen-free) areas. The laboratory is approved by the State Food and Veterinary Service for breeding and selling as well as experimental work with animals. The highly qualified staff hold all the necessary certificates for animal research. Some facilities, including a fully equipped operating room and laboratory for working with animal specimens are open to all scientists who have the right to work with animals. In this laboratory, heart failure research is carried out, studies of biocompatibility and toxicological tests are being performed.              

Projects 2012-2017:

1. ”Soft tissue engineering: from cell to artificial tissue“, 2015-2018, funded by the Research Council of Lithuania. Head dr. D. Baltriukienė.
2. ”Construction of composite bone scaffold material and in vivo evaluation of biocompatibility and osteopromotion“, 2015-2018, funded by the Research Council of Lithuania. Head dr. V. Rutkūnas.
3. ”Significance of titin ligands MuRF and C ARP in dilated myocardium“, 2014-2016, funded by the Research Council of Lithuania. Head prof. V. Grabauskienė.
4. ”Molecular mechanisms of the toxicity and antitumor activity of quinones and polyphenols: enzymatic redox reactions, cytotoxicity, signal transduction and proteomics“ 2011-2015, funded via the Global Grant measure, managed using EU funding. Head habil. dr. N. Čėnas.
5. ”Molecular processes in eukaryotic cells: technological and medical aspects”, 2012-2015, funded by the EU support program „Biotechnology and biopharmacy: fundamental and applied research“. Head prof. R. Navakauskienė.
6. ”Biocatalysts, recombinant proteins and cell technologies”, 2012-2014, funded by the EU support program „Biotechnology and biopharmacy: fundamental and applied research“. Head prof. J. Kulys.
7. “Evaluation of gingival fibroblast adhesion properties and their use in regeneration of soft tissue”, 2011-2012, funded by the Research Council of Lithuania, head dr. E. Liutkevičius.

Main publications 2012-2017:

1. Jarasiene-Burinskaja R., M. Alksne, Bartuskiene,  V. Voisniene, J. Burinskij., N. Cenas, V. Bukelskiene. Study of the cytotoxic effects of 2,5-diaziridinyl-3,6-dimethyl-1,4-benzoquinone (MEDZQ) in mouse hepatoma cells. EXCLI Journal. 2017, Vol. 16, p. 151-159.
2. Valiuliene G., G. Treigyte, J. Savickiene, D. Matuzevicius, M. Alksne, R. Jarašiene-Burinskaja, V. Bukelskiene, D. Navakauskas, R. Navakauskiene. Histone modifications patterns in tissues and tumours from acute promyelocytic leukemia xenograft model in response to combined epigenetic therapy. Biomedicine & Pharmacotherapy, 2016, Vol. 79, 62-70.
3. Bogomolovas J., E. Šimoliūnas, I. Rinkūnaitė,L. Smalinskaitė, A. Podkopajev, D. Bironaitė, -A. Weis, A. Marx, V. Bukelskienė, N. Gretz, V. Grabauskienė, D. Labeit, S. Labeit. A Novel Murine Model of Parvovirus Associated Dilated Cardiomyopathy Induced by Immunization with VP1-Unique Region of Parvovirus B19. Biomed Research International, 2016, Article Number: 1627184.   
4. Rutkunas V., V. Bukelskiene, V. Sabaliauskas, E. Balciunas, M. Malinauskas, D. Baltriukiene. Assessment of human gingival fibroblast interaction with dental implant abutment materials. Journal of materials science-materials in medicine, 2015, 26 (4), Article Number: 169.
5. Bogomolovas J., K. Brohm, J. Čelutkienė, G. Balčiūnaitė, D. Bironaitė, V. Bukelskienė, Daunoravičus, Ch.C. Witt, J. Fielitz, V. Grabauskienė, S. Labeit. Induction of Ankrd1 in Dilated Cardiomyopathy Correlates with the Heart Failure Progression. Biomed research international , 2015, Article Number: 273936.
6. Malinauskas M., S. Rekštytė, L. Lukoševičius, S. Butkus, E. Balčiūnas, M. Pečiukaitytė, Baltriukienė, V. Bukelskienė, A. Butkevičius, P. Kucevičius, V. Rutkūnas, S. Juodkazis. 3D Microporous Scaffolds Manufactured via Combination of Fused Filament Fabrication and Direct Laser Writing Ablation. Micromachines, 2014, Vol. 5 (4), p. 839-858.
7. Baltriukiene D., V. Sabaliauskas, E. Balčiūnas, A. Melninkaitis, E. Liutkevičius, V. Bukelskiene, V. Rutkūnas. The effect of laser-treated titanium surface on human gingival fibroblast behavior. Journal of biomedical materials research, Part A, 2014, 102 (3), p. 713-720.
8. Kalvelyte A., N. Krestnikova, A. Stulpinas, V. Bukelskiene, D. Bironaite, D. Baltriukiene, A. Imbrasaite. Long-term muscle-derived cell culture: multipotency and susceptibility to cell death stimuli. Cell biology international, 2013, 37 (4), p. 292-304.
9. Danilevičius P., S. Rekstytė, E. Balčiūnas, A. Kraniauskas, R. Širmenis, D. Baltriukienė, V. Bukelskienė, R. Gadonas, V. Sirvydis, A. Piskarskas, M. Malinauskas. Laser 3D micro/nanofabrication of polymers for tissue engineering applications. Optics and laser technology, 2013, 45, p. 518-524.
10. Danilevicius P.; S. Rekstyte; E. Balciunas; A. Kraniauskas; R. Jarasiene; R. Sirmenis; D. Baltriukiene; V. Bukelskiene; R. Gadonas; M. Malinauskas. Micro-structured polymer scaffolds fabricated by direct laser writing for tissue engineering. Journal of biomedical optics, 2012, Vol. 17 (8), Article Number: 081405.

Department of Molecular Cell Biology

Head prof. Rūta Navakauskienė
phone: +37052234409
email: 

Research interests

We study the molecular mechanisms of normal, cancer and stem cells functioning in order to determine new possibilities in cancer therapy and regenerative medicine. Studies are designed to predict the outcome of treatment in in vitro models and in the individual cases (Personalized Cancer Therapy):

• Evaluation of proliferation, differentiation and apoptosis signaling in human cancer and stem cells in in vitro and in vivo models
• Determination of epigenetic regulation in stem cells during self-renewing and differentiation
• Manipulation of signaling molecules in chemotherapeutic drugs-induced pathway for establishment of new strategies for targeted anti-cancer treatment of many tumors
  

Research resources and services/Offer

Cancer and stem cell culturing (isolation, cultivation, differentiation), Flow cytometry analysis (sample preparation and analysis, cell cycle checkpoints), Protein fractionation one or two dimensional electrophoresis (SDS/PAGE and 2DE, further preparation for mass spectrometry analysis), Real-time PCR analysis, Epigenetic markers (histone modifications, DNA methylation), Chromatin immunoprecipitation (sonication, ChIP and PCR), Microscopy, Cytoxicity evaluation and signaling mechanisms determination in cellular models.

Research projects 2012-2017

Project Supported by University Budget

Studies of regulatory mechanisms of cancer and stem cell for new technologies of personalized medicine. Prof. R. Navakauskienė. 2014-2018.

Projects Supported by Research Council of Lithuania (2012-2017):

National Science program project „Multiplexed molecular biomarker study for leukemia“ (No. LIG-06-2012) Prof. Rūta Navakauskienė. 2012-2014

National Science program project “Bee products enriched with plant components, the composition and properties”(No. SVE-01/2012) Dr. Bogumila Kurtinaitienė.  2012-2015

“Cytological, molecular and epigenetic studies of amniotic fluid” (No. MIP-033/2013) Dr. Gražina Treigytė. 2013-2015

National Science program project “The role of molecular modulators in the hematological system during cell senescence, differentiation and regeneration”  (No. SEN-12/2015) Prof. Rūta Navakauskienė. 2015–2018.

“Regulation of amniotic fluid‐derived stem cell functioning by microRNA and epigenetic factors” (No. MIP-57/2015) Dr. Jūratė Savickienė. 2015-2018.

Projects Supported by EU funding:

”Molecular processes in eukaryotic cells: technological and medical aspects”, 2012-2015, funded by the EU support program „Biotechnology and biopharmacy: fundamental and applied research“. Head prof. R. Navakauskienė.

”Molecular mechanisms of the toxicity and antitumor activity of quinones and polyphenols: enzymatic redox reactions, cytotoxicity, signal transduction and proteomics“. 2011-2015, funded via the Global Grant measure, managed using EU funding.  Head habil. dr. N. Čėnas.

International Research Projects (2012-2017):

CM1106 Chemical approaches to targeting drug resistance in cancer stem cells (StemChem). Prof. R. Navakauskienė.  2011-2015

BM1402 Development of a European network for preclinical testing of interventions in mouse models of age and age-related diseases (MouseAGE). Prof. R. Navakauskienė. 2014-2018.

CA15138 European Network of Multidisciplinary Research and Translation of Autophagy knowledge (TRANSAUTOPHAGY). Dr. Veronika Borutinskaitė. 2015- 2019.

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

Vilnius Gediminas Technical University, Linkoping University (Sweden), Nice University (France), Milan University (Italy), Malta University (Malta), Northwestern University (USA)

Main publications (2012-2017):

1. Navakauskienė R. Combination Epigenetic Therapy. Handbook of Epigenetics. The new molecular and medical genetics. 2nd Edition, Edited by T.O.Tollefsbol, 2017, Chapter 41, p. 623-632, Elsevier ISBN: 978-0-12-805388-1.
2. Audrone V. Kalvelyte, Aušra Imbrasaite, Natalija Krestnikova, Aurimas Stulpinas. Adult Stem Cells and Anticancer Therapy. Advances in Molecular Toxicology, 1st Edition, Volume 11, Chapter Four.  Pages  124 – 202. Published date: 2nd October 2017. Edited by J.C. Fishbein and J.M. Heilman, Elsevier ISBN: 9780128125229.
3. Borutinskaitė V, Virkšaitė A, Gudelytė G, Navakauskienė R. Green tea polyphenol EGCG causes anti-cancerous epigenetic modulations in acute promyelocytic leukemia cells. Leuk Lymphoma. 2018 Feb;59(2):469-478.
4. Abdelwahid E, Stulpinas A, Kalvelyte A. Effective agents targeting the mitochondria and apoptosis to protect the heart. Current Pharmacological Design, 2017, 23(8): 1153-1166. ISSN 1873-4286.
5. Valiulienė G, Stirblytė I, Jasnauskaitė M, Borutinskaitė V, Navakauskienė R. Anti-leukemic effects of HDACi Belinostat and HMTi 3-Deazaneplanocin A on human acute promyelocytic leukemia cells. European Journal of Pharmacology. 2017 Mar 15;799:143-153.
6. Savickienė J., Baronaitė S., Zentelytė A., Treigytė G., Navakauskienė R. Senescence-associated molecular and epigenetic alterations in mesenchymal stem cell cultures from amniotic fluid of normal and fetus-affected pregnancy. Stem Cells International. 2016, vol. 2016. Article ID 2019498.
7. Glemžaitė M. and Navakauskienė R. Osteogenic differentiation of human amniotic fluid mesenchymal stem cells is determined by epigenetic changes. Stem Cells International. 2016. Article ID 6465307.
8. Stulpinas A., Imbrasaitė A., Krestnikova N., Šarlauskas J., Čėnas N., Kalvelytė A.V. Study of Bioreductive Anticancer Agent RH-1-Induced Signals Leading the Wild-Type p53-Bearing Lung Cancer A549 Cells to Apoptosis. Chemical Research in Toxicology. 2016, 29(1): 26-39.
9. Abdelwahid E., Kalvelyte A., Stulpinas A., de Carvalho K.A., Guarita-Souza L.C., Foldes G. Stem cell death and survival in heart regeneration and repair. Apoptosis. 2016, 21(3): 252-268.
10. R. Navakauskienė, M. Mori, M. S. Christodoulou, A. Zentelytė, B. Botta, L. Dalla Via, F. Ricci, G. Damia, D. Passarella, C. Zilio and N. Martinet. Histone demethylating agents as potential S-adenosyl-L-methionine-competitors. Medicinal Chemical Communications. 2016, vol. 7 (6), p. 1245-1255.
11. R. Navakauskiene, S. Baronaite, D. Matuzevicius, I. Zaikova, A. Arlauskiene, D. Navakauskas, G. Treigyte. Identification and Characterization of Amniotic Fluid Proteins Incident to Normal, Preeclampsia and Polyhydramnios Pregnancies. Current Proteomics. 2016, vol. 13 (3), p. 206-217.
12. Borutinskaitė V, Navakauskienė R. 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. 2015 Aug 6;16(8):18252-69.
13. Krestnikova N., Stulpinas A., Imbrasaite A., Sinkeviciute G., Kalvelyte A.V. JNK implication in adipocyte-like cell death induced by chemotherapeutic drug cisplatin. The Journal of Toxicological Sciences, 2015, 40(1): 21-32.
14. R. Navakauskiene, V.V. Borutinskaite, G. Treigyte, J. Savickiene, D. Matuzevicius, D. Navakauskas, K.-E. Magnusson. Epigenetic changes during hematopoietic cell granulocytic differentiation--comparative analysis of primary CD34+ cells, KG1 myeloid cells and mature neutrophils. BMC Cell Biology 2014, vol. 15(4), p. 938-949.
15. Navakauskiene R., Treigyte G., Borutinskaite V., Matuzevicius D., Navakauskas D., Magnusson K.-E. Alpha-Dystrobrevin and its associated proteins in human promyelocytic leukemia cells induced to apoptosis. Journal of Proteomics. 2012, vol. 75, p. 3291-3303.
16. Kalvelyte A., N. Krestnikova, A. Stulpinas, V. Bukelskiene, D. Bironaite, D. Baltriukiene, A. Imbrasaite. Long-term muscle-derived cell culture: multipotency and susceptibility to cell death stimuli. Cell Biology International. 2013, Vol. 37 (4), p. 292-304.
17. Stulpinas A., Imbrasaitė A., Kalvelytė A.V. Daunorubicin induces cell death via activation of apoptotic signalling pathway and inactivation of survival pathway in muscle-derived stem cells. Cell Biology and Toxicology. 2012, Vol. 28 (2), p.103–114.

Department of Molecular Microbiology and Biotechnology

Head dr. Rolandas Meškys
phone: +370 5 223 4386
email:

Microbial diversity both genetic and biochemical is incredible resource of different proteins and biocatalysts. Analysis and exploration of such diversity is one of the main aim of our group. The studies are concentrated in several fields.

The first one is related to isolation of N-heterocyclic compounds-utilising microorganisms and investigation of catabolic pathways of these compounds in individual bacteria. Both genetic and biochemical characterization of bioconversion processes are carried out. The identified novel oxygenases as well as other enzymes participating in the biodegradation are tested as biocatalysts for organic chemistry.

The modified nucleotides are ones of the many substrates, whose catabolism is being elucidated. In addition, the studies of biosynthetic pathways of wyosine, a modified nucleotide base, is also our activity.

Screening of novel enzymes is also carried out by application of metagenomic techniques, specific and effective selection systems combined with tailored substrates. In cooperation with other groups both from Vilnius University and international, the screened enzymes are used for development of biosensors, biofuel-cells and for synthesis of industry-related chemical compounds.

The second major field of our activities is associated with studies of bacteriophages active towards various gram-negative and gram-positive bacteria. We are interested in elucidation of structural diversity of bacteriophages, initial stages of the infection process and the identification of self-assembling proteins applicable for construction of the hybrid nanoparticles.

We are experts in discovering of enzymes including hydrolases, oxidoreductases and transaminases. Metagenomic libraries combined with the “smart” substrates that are developed and synthesized in our group is a technology, which offers an efficient screening and selection of novel biocatalysts applicable for bioconversion, organic syntheses and development of biosensors as well as biofuel cells. Our team is also skilled in isolation and identification of bacteriophages as a source of proteins predisposed to form self-assembling structures and important for the biomedical application.

Key grants (2012–2017):

National Research Projects funded by Research Council of Lithuania:

Development of methods for screening and expression of Baeyer-Villiger monooxygenases. (MIP-042/2012) Dr. R. Meškys. 2012–2014.

tRNA modification pathways – evidence of the enzyme evolution. (MIP-043/2012) Dr. J. Urbonavičius. 2012–2014.

European Social Fund (ESF) under the Human Resources Development Action Programme, the Global Grant measure, project No. VP1-3.1-ŠMM-07-K-03-015. Change or die: redesign of oxidoreductases (CHORD). Dr. R. Meškys. 2013–2015.

Proteogenomics of the early infection stages of virulent Escherichia coli bacteriophages. (MIP-002/2014) Dr. L. Truncaitė. 2014–2016.

Screening and analysis of novel enzymes participating in catabolism of modified uracil base and nucleosides (MIP-103/2015) Dr. J. Urbonavičius. 2015–2017.

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

International Research Projects:

EU Horizon2020 Program. H2020-BG-2014-2. Industrial Applications of Marine Enzymes: Innovative screening and expression platforms to discover and use the functional protein diversity from the sea (INMARE). Dr. R. Meškys. 2015–2019.

Contractual Research:

Bayer Technology Services GmbH (Germany), Amilina AB (Lithuania), Baxalta Innovation GmbH (Austria). Dr. R. Meškys.

Key publications (2012–2017):

1. Šimoliūnas E., Kalinienė L., Truncaitė L., Zajančkauskaitė A., Staniulis J., Kaupinis A., Ger M., Valius M., Meškys, R. Klebsiella phage vB_KleM-RaK2 - a giant singleton virus of the family Myoviridae. PLOS One 2013 8(4): e60717.
2. Kutanovas S, Stankeviciute J, Urbelis G, Tauraite D, Rutkiene R, Meskys R. Identification and characterization of tetramethylpyrazine catabolic pathway in Rhodococcus jostii TMP1. Appl. Environ. Microbiol. 2013 79: 3649–3657.
3. Urbonavičius J., Meškys R., Grosjean H. Biosynthesis of wyosine derivatives in tRNAPhe of Archaea: role of a remarkable bifunctional tRNAPhe:m1G/imG2 methyltransferase. RNA 2014 20:747–753.
4. Šimoliūnas E., Kaliniene L., Stasilo M., Truncaitė L., Zajančkauskaitė A., Staniulis J., Nainys J., Kaupinis A., Valius M., Meškys R. Isolation and characterization of vB_ArS-ArV2 – first Arthobacter sp. infecting bacteriophage with completely sequenced genome. PLoS One 2014 9(10): e111230.
5. Povilonienė S., Časaitė V., Bukauskas V., Šetkus A., Staniulis J., Meškys R. Functionalization of alpha-synuclein fibrils. Beilstein J. Nanotech. 2015, 6: 124–133.
6. Stankevičiūtė J., Kutanovas S., Rutkienė R., Ražanas R., Tauraitė D., Striela R., Meškys R. Ketoreductase TpdE from Rhodococcus jostii TMP1: characterization and application in the synthesis of chiral alcohols. PeerJ 2015 3: e1387.
7. Vaitekūnas J., Gasparavičiūtė R., Rutkienė R., Tauraitė D., Meškys R. A 2-hydroxypyridine catabolism pathway in Rhodococcus rhodochrous strain PY11. Appl. Environ. Microbiol. 2016 82: 1264–1273.
8. Stankevičiūtė J., Vaitekūnas J., Petkevičius V., Gasparavičiūtė R., Tauraitė D., Meškys R. Oxyfunctionalization of pyridine derivatives using whole cells of Burkholderia sp. MAK1. Sci. Rep. 2016 6: 39129.
9. Urbonavičius J., Rutkienė R., Lopato A., Tauraitė D., Stankevičiūtė J., Aučynaitė A., Kaliniene L., van Tilbeurgh H., Meškys R. Evolution of tRNAPhe:imG2 methyltransferases involved in the biosynthesis of wyosine derivatives in Archaea. RNA 2016 22: 1871-1883.
10. Dagys M., Laurynėnas A., Ratautas D., Kulys J., Vidžiūnaitė R., Talaikis M., Niaura G., Marcinkevičienė L., Meškys R., Shleev S. Oxygen electroreduction catalyzed by laccase wired to gold nanoparticle via trinuclear copper cluster. Energy Environ. Sci. 2017, 10: 498–502.
11. Tetianec L., Chaleckaja A., Kulys J., Janciene R., Marcinkeviciene L., Meskiene R., Stankeviciute J., Meskys R. Characterization of methylated azopyridine as a potential electron transfer mediator for electroenzymatic systems. Process Biochem. 2017 54: 41–48.
12. Kaliniene L., Šimoliūnas E., Truncaitė L., Zajančkauskaitė A., Nainys J., Kaupinis A., Valius M., Meškys R. Molecular analysis of Arthrobacter myovirus vB_ArtM-ArV1: we blame it on the tail. J. Virol. 2017 91: e00023-17.
13. Tauraitė D., Jakubovska J., Dabužinskaitė J., Bratchikov M., Meškys R. Modified nucleotides as substrates of terminal deoxynucleotidyl transferase. Molecules 2017 22(4), 672.
14. Sadauskas M, Vaitekūnas J, Gasparavičiūtė R, Meškys R. Indole biodegradation in Acinetobacter sp. strain O153: genetic and biochemical characterization. Appl. Environ. Microbiol. 2017 83 (19): e01453-17.

Department of Xenobiotics Biochemistry

Head habil. dr. Narimantas Čėnas
phone: +370 5 223 4392
email:

Main research directions. Synthesis of prooxidant xenobiotics (quinones, aromatic nitrocompounds, N-oxides, etc.), studies of interaction of these compounds with flavoenzymes and their impact on their cytotoxicity, mechanisms of flavoenzyme catalysis, prooxidant cytotoxicity of polyphenolic compounds. Since 1992, the Department collaborates with research centers in Lithuania, Belarus, Great Britain, Spain, Italy, USA, New Zealand, the Netherlands, France, Sweden, and Ukraine.  We have participated in projects supported by the EC (2), NATO (2), the Royal Swedish Academy of Sciences (1),   bilateral projects with France (2), Belarus (1), and Ukraine (1), COST actions (4), received a number of grants from LSSSF and RCL including the project funded by European Social Fund (ESF) under the Human Resources Development Action Programme, the Global Grant measure (2011-2015).

Synthesis of prooxidant compounds. We have synthesized or resynthesized over 300 compounds of different groups  – nitroaromatic and nitroheterocyclic compounds, aliphatic nitrates, aromatic N-oxides, quinones, benzofuroxans, etc. (Fig. 1), examined their electrochemical properties and characterized their reduction energetics by quantum-mechanical methods.

Fig. 1. High-energy substances tetryl (1), keto-RDX (2), PETN (3), and other groups of compounds: nitrobenzimidazolonesi (4), aziridinyl-substituted quinones (5) and nitrobenzenes (6), nitrofurans (7), benzofuroxanes (8), di-N-oxides of quinoxaline (9) and 1,2,4-benzotriazine (10), and heterocyclic oximes (11).

The mechanisms of single- and two-electron reduction of quinones, nitroaromatic compounds, and other prooxidants by flavoenzymes. Flavoenzymes  electrontransferases reduce quinones, aromatic nitrocompounds and N-oxides into their free radicals. The latter are reoxidized by  oxygen with the formation of superoxide and other reactive oxygen species (ROS) causing the oxidative stress which significantly determines their cytotoxicity , antitumour and other therapeutic activity of the compounds.  The enzymatic single-electron reduction reactions of the compounds have been examined applying mammalian cytochrome P-450 reductase, NO-synthase (in collaboration with J.-L. Boucher, Universite de Paris V), Anabaena sp. and P. falciparum ferredoxin:NADP⁺ reductase (in collaboration with C. Gomez-Moreno, Universidad de Zaragoza, and A. Aliverti, Universita de Milano), and mixed single- and two-electron reduction reactions by using mammalian mitochondrial complex I (in collaboration with A.D. Vinogradov, Moscow University), apoptosis inducting factor (in collaboration with I.F. Sevrioukova,  California University, Irvine), lipoamide dehydrogenase, plant and bacterial thioredoxin reductases (in collaboration with J.-P. Jacquot and N. Rouhier, Universite de Nancy), and bacterial flavohemoglobin (in collaboration with L. Baciou and F. Lederer, Universite de Paris Sud). The single-electron reduction of quinones and nitroaromatic compounds by aforementioned enzymes is described by Marcus' model, and the rates are weakly influenced by the structure and VdWvol of the compounds.  In several cases, the redox states of the enzymes responsible for the rate-limiting stage have been identified.  Mixed single- and two-electron reduction is characterized by  e^-,H⁺,e^-  mechanism determined by the destabilization of neutral flavin semiquinone.

Two-electron reduction by mammalian DT-diaphorase or bacterial  nitroreductases decreases the cytotoxicity of simple quinone compounds, but increases the cytotoxicity of aziridinyl-substituted quinones and nitroaromatic compounds due to formation of DNA-alkylating products (Fig. 2).

Fig. 2. Two-electron reduction of aziridinyl-substituted quinones with subsequent alkylation of DNA.

It has been examined the reduction of quinones and nitroaromatic compounds mediated by DT-diaphorase, E. cloacae nitroreductase B (in collaboration with R. Koder, Kentucky University), PETN reductase (in collaboration with N.S. Scrutton, Manchester University), and E. coli nitroreductase A (in collaboration with D.F. Ackerley, Welington University). These reactions have been found to be characterized by a strong substrate structure specificity because of significant conformational changes of the enzyme active sites and by negative ∆S^≠. Depending on the stability of anionic flavin semiquinone radical, these reactions proceed through single-  (H^-) or three-step (e^-,H⁺,e^-) hydride transfer.

Mammalian cell culture cytotoxicity of quinones and nitroaromatic compounds. Applying several transformed and primary mammalian cell cultures (Center of Innovative Medicine), the cytotoxic action of quinones and nitroaromatics has been found to be mainly determined by the oxidative stress, and that the cytotoxicity of compounds increases with an increase in their single-electron reduction potential, with ∆log cL₅₀/∆E¹₇  of  -8 – -10 V^-1. Significantly increased cytotoxicity of aziridinyl-substituted quinones is attributed to their activation by DT-diaphorase. Aziridinyl-benzoquinone resistant cell sub-lines possess 10-fold decreased activity with DT-diaphorase and glutathione-S-transferase, whereas the activity of prooxidant and antioxidant enzymes varies in the limits of ±50%. 

Quinones and nitroaromatic compounds as inhibitors and subversive substrates of antioxidant flavoenzymes.  Quinones and nitroaromatic compounds inhibit the antioxidant mammalian and parasite flavoenzymes glutathione reductase (GR) and trypanothione reductase (TR), and mammalian thioredoxin reductase (TrxR), thus inhibiting the regeneration of –SH groups in the cell.  In parallel, they may be reduced by the aforementioned enzymes in mixed single- and two-electron way, thus subverting their antioxidant functions.  The above mechanisms may be employed in the design of new antiparasitic and anticancer agents. The interaction of the above compounds has been examined with erythrocyte and P. falciparum GR (in collaboration with E. Davioud-Charvet, Universite de Strasbourg), T. congolense TR (in collaboration with J. Blanchard,  Albert Einstein College of Medicine, NY), and mammalian TrxR (in collaboration with E. Arner, Karolinska Institutet). A number of efficient inhibitors of the above enzymes have been discovered. It has been established that apart from the reduced flavin, the above compounds may be reduced by the catalytic SeH-SH-moiety of TrxR. In collaboration with P. Grellier (MNHN, Paris), the relation between the efficiency of inhibition of P. falciparum GR by quinones and nitroaromatic compounds and their in vitro antiplasmodial activity has been established.

Prooxidant cytotoxicity of polyphenols. The antioxidant activity of polyphenols (flavonoids, polihydroxybenzenes, etc.) relies on neutralization of ROS. Therefore they are considered as useful food components; their antitumour and antiparasitic activity have been examined. However, polyphenols possess prooxidant cytotoxicity, because during their (auto)oxidation, H₂O₂ and quinone/quinomethide oxidation products are formed which alkylate –SH groups in the cell. The cytotoxicity of polyphenols in several cell lines increases with a decrease in their single-electron oxidation potential (∆log cL₅₀/∆E²₇ = 1 – 2 V^-1 ), and with an increase in their lipophilicity. Hydroxylation and oxidative demethylation of polyphenols by cytochromes P-450 increases their cytotoxicity, whereas the methylation by catechol-O-methyltransferase decreases it. During the collaboration with P. Venskutonis (Kaunas Technological University), prooxidant cytotoxicity of a number of plant and herb polyphenolic extracts has been characterized.

Key grants 2012-2017

 National Research Projects funded by Research Council of Lithuania

1. Heterocyclic N-oxides: synthesis, cytotoxicity, and interaction with target enzymes (MIP-080/2011). Dr. J. Šarlauskas. 2011-2012.
2. 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 antitumor activity of quinones and polyphenols: enzymatic redox reactions, cytotoxicity, signal transduction and proteomics. Habil. Dr. N. Čėnas. 2011–2015.
3. New generation N-heterocyclic quinones: rational synthesis and elucidation of anticancer activity (MIP-032/2014). Dr. Ž. Anusevičius. 2014-2016.

International Research Projects 

1. COST Action CM0801. New drugs for neglected diseases. Dr. J. Šarlauskas. Habil. Dr. N. Čėnas. 2009-2012.
2. COST Action CM1307. Targeted chemotherapy towards diseases by endoparasites. Dr. J. Šarlauskas. Habil. Dr. N. Čėnas. 2014-2017.
3. Bilateral Lithuanian-French programme Gilibert. Quinones and nitroaromatic compounds as the subversive substrates of flavohemoglobins: mechanisms and biomedicinal implications (No. TAP LZ 07/2013). Habil. Dr. N. Čėnas 2013-2014.
4. Bilateral Lithuania-Belarus programme. The characterization of the inter-protein interaction and the modulators of the redox equivalent transfer in steroid hydroxylation systems (No. TAP LB 02/2013). Dr. Ž. Anusevičius. 2013-2014.
5. 5. Bilateral Lithuania-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.

Key publications 2012-2017

1. Valiauga, E.M. Williams, D.F. Ackerley, N. Čėnas (2017). Reduction of quinones and nitroaromatic compounds by Escherichia coli nitroreductase A (NfsA): characterization of kinetics and substrate specificity. Arch. Biochem. Biophys. 614,14-22.
2. Smutok O., M. Karkovska, R. Serkiz, B. Vus, N. Čėnas, M. Gonchar (2017). A novel mediatorless biosensor based on flavocytochrome b(2) immobilized onto gold nanoclasters for non-invasive L-lactate analysis of human liquids. Sensors and Actuators, 250, 469-475.
3. Pečiukaityte-Alksnė, J. Šarlauskas, L. Misevičienė, A. Marozienė, K. Krikštopaitis, N. Čėnas, K. Krikštopaitis, Z. Staniulytė, Ž. Anusevičius (2017). Flavoenzyme-mediated reduction reactions of nitrogen-containing tetracyclic ortho-quinone compounds and their nitrated derivatives. EXCLI J. 16, 663-678.
4. Šarlauskas, J. Tamulienė, N. Čėnas (2017). Aziridinyl-substituted benzo-1,4-quinones: a preliminary investigation on the theoretical and experimental studies of their structure and spectroscopic properties. Spectrochim. Acta 178, 136-141.
5. Jarasiene-Burinskaja, M. Alksne, V. Bartuskiene,  V. Voisniene, J. Burinskij., N. Cenas, V. Bukelskiene (2017). Study of the cytotoxic effects of 2,5-diaziridinyl-3,6-dimethyl-1,4-benzoquinone (MEDZQ) in mouse hepatoma cells. EXCLI J. 2017,16, 151-159.
6. Šarlauskas, M. Pečiukaitytė-Alksnė, L. Misevičienė, A. Marozienė, E. Polmickaitė, Z. Staniulytė, N. Čėnas, Ž. Anusevičius (2016). Naphtho[1',2':4,5]imidazo[1,2-a]pyridine-5,6-diones:synthesis, enzymatic reduction and cytotoxicity. Bioorg. & Med. Chem. Lett. 26, 512-517.
7. Ger, A. Kaupinis, A. Nemeikaite-Čėnienė, J. Šarlauskas, J. Cicėnas, N. Čėnas, M. Valius (2016). Quantitative proteomic analysis of anticancer drug RH1 resistance in liver carcinoma. Biochim. Biophys. Acta 1864, 219-232.
8. Stulpinas, A. Imbrasaitė, N. Krestnikova, J. Šarlauskas, N. Čėnas, A.V. Kalvelytė (2016). Study of bioreductive anticancer agent RH-1-induced signals leading the wild-type p53-bearing lung cancer A549 cells to apoptosis. Chem. Res. Toxicol. 29, 26-39.
9. Valiauga, N. Rouhier, J.-P. Jacquot, N. Čėnas (2015). Quinone- and nitroreductase reactions of Thermotoga maritima thioredoxin reductase. Acta Biochim. Polon. 62, 303-309.
10.   Kosychova, A. Karalius, Z. Staniulytė, R.A. Sirutkaitis, A. Palaima, A. Laurynėnas, Ž. Anusevičius (2015) New 1-(3-nitrophenyl)-5,6-dihydro-4H-[1,2,4]triazolo[4,3a][1,5]benzodiazepines: synthesis and computational study. Molecules 20, 5392-5408.
11. Miliukienė, H. Nivinskas, N. Čėnas (2014) Cytotoxicity of anticancer aziridinyl-substituted benzoquinones in primary mice splenocytes. Acta Biochim. Polon. 61, 833-836.
12. Šarlauskas J., L. Misevičienė, A. Marozienė, L. Karvelis, J. Stankevičiūtė, K. Krikštopaitis, N. Čėnas, Yantsevich, A. Laurynėnas, Ž. Anusevičius (2014). The study of NADPH-dependent flavoenzyme-catalyzed reduction of benzo[1,2-c]1,2,5-oxadiazole N-oxides (benzofuroxans). Int. J. Mol. Sci. 15, 23307-23331.
13. Ž. Anusevičius, H. Nivinskas, M.A. Sari, J.-L. Boucher (2013) Single-electron reduction of quinone and nitroaromatic  xenobiotics by recombinant rat neuronal nitric oxide synthase. Acta Biochim. Polon. 60, 217-222.
14. Ž. Anusevičius, L. Misevičienė, J. Šarlauskas, N. Rouhier, J.-P. Jacquot, N. Čėnas (2012) Quinone-and nitroreductase reactions of Thermotoga maritima peroxiredoxin-nitroreductase hybrid enzime. Biochem. Biophys. 528, 50-56.

Laboratory of Bioorganic Compounds Chemistry

Head dr. Regina Jančienė
phone: +37052729058
email:

The Laboratory of Bioorganic Compounds Chemistry is a non-academic unit of the VU LSC Institute of Biochemistry, which carries out activities at the Section of Experimental Production located in Mokslininku Street, Vilnius. Besides research laboratories, the Section of Experimental Production has facilities and equipment for large volume organic synthesis and a separate unit adapted for high-pressure reactions.

Research interests of Laboratory of Bioorganic Compounds Chemistry are the synthesis of amino acids and their derivatives, the search of synthesis pathways and the development of technologies for macrocyclic and linear polyethers and investigation of the synthesis, structural and other properties of various heterocycles. Since 2014 the main activities of Laboratory focused on the contractual projects. These studies are carried out in cooperation with Lithuanian and foreign business entities who are interested in introducing the results of research into practice. Our partners are Ramidus AB (Sweden), Synthon Chemicals GmbH (Germany), Polypure AS (Norway), Bapeks Ltd. (Latvia), Thermofisher Scientific Baltics UAB (Lithuania), UAB Elymus, (Lithuania), UAB Biotecha (Lithuania), UAB Ekorama (Lithuania), UAB Vilniaus Ventas Semiconductors (Lithuania).

Current aim of our laboratory is closing the gap from laboratory to market via pilot-scale development.  This activity enables to demonstrate the commercial potential of the new technology.

The applied scientific research can be conducted both in laboratory and reactor scale. Our equipment includes different volume glass (20-100 L), glass-lined (10-1600 L) and stainless steel reactors (10-600 L), as well as autoclaves for catalytic hydrogenation (0.2-10 L) and different kinds of auxiliary equipment.

We offer services to fellow scientists and business representatives in the field of organic synthesis:

• Development and optimization of technologies for the synthesis of chemical compounds
• Testing of scalability of chemical technology designed by interested developers
• Investigation of synthesis methods for organic compounds of different classes, development and design of multi-step synthesis schemes
• Custom synthesis of fine chemicals for research, commerce and industry

Our product portfolio contains over 200 compounds of various classes:

O,N ir S-heterocyclic compounds

thiols, thioethers and thioamides

stereoisomeric disubstituted cyclohexane derivativesi

aromatic carboxylic acids

aminoacid derivatives

mono- and disubstituted cyclic polyethers

aminonaphthalensulfoamides

monodisperse derivatives of polyethylene glycols

enzyme cofactors

These high quality fine chemicals for scientific and commercial purposes are produced from grams to hundreds of kilograms, depending on the compounds structure and requirement of the customers.

Proteomics Centre

Head dr. Mindaugas Valius
phone: +37052234410
email:  

Research interests

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

Projects

• Research Council of Lithuania. High throughput proteomics for cancer cell surface protein recognition by quantum dots. Dr. M. Valius, 2014–2016.
• Agency for Science, Innovation and Technology. Creation of biologically active regular three-dimensional structures for tissue molecular bioengineering, Dr. M. Valius, 2012-2013
• Participation in Global grant „Molecular mechanisms of the toxicity and antitumour activity of quinones and polyphenols: enzymatic redox reactions, cytotoxicity, signal transduction and proteomics “, Habil. Dr. N. Čenas (Dept. Xenobiotics Biochemistry), 2011-2015
• Participation in the project supported by the European Social Fund under National Integrated Programme. Biotechnology and Biopharmacy: fundamental and applied research, 2012-2015. Action 1.1.3. Molecular processes in eukaryotic cells: the technological and medical aspects. Head of Action Prof. Dr. R. Navakauskienė (Dept. Mol. Cell Biology).