Institute of Biochemistry

Institute of Biochemistry

Sukurta: 30 July 2017

bchi7 Saulėtekio, LT-10257
Tel. 223 4378
E-mail:
http://www.bchi.vu.lt

Director - Dr. Kastis Krikštopaitis

STAFF

64 research fellows (incl. 56 holding research degree), 24 doctoral students.

 

 


RESEARCH AREAS

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

MAIN CONFERENCES ORGANIZED IN 2016

20th conference “Laboratory Animals in Research”


DEPARTMENT OF BIOANALYSIS

7 Saulėtekio, LT-10257
Tel. 223 43 89
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 (completed studies in 2016), J. Gružauskaitė, D. Ratautas, L. Rekovič, 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 2016

Project Supported by University Budget

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

Different oxidoreductases were applied for the creation of mediatorless bio-anodes and bio-cathodes in bio-solar cells, bio-batteries and bio-fuel cells.

Main publication:

Ratautas, D., Laurynėnas, A., Dagys, M., Marcinkevičienė, L., Meškys, R., Kulys, J. 2016. High current, low redox potential mediatorless bioanode based on gold nanoparticles and glucose dehydrogenase from Ewingella Americana. Electrochimica Acta, vol. 199, p. 254–260.

Nanostructurized carbonatious matrixes for effective electron transfer in bio-electrocatalysis.   

Oxidized graphites (OG), thermally reduced graphene oxides or nanocomposite materials have been prepared and studied aiming to obtain and further to apply the nanostructures as effective electrode material for effective oxygen reduction (OR) or reagentless enzyme electrodes in which electron transfer between electrode and enzyme active site proceeds directly, without any additional mediators. Novel electrochemical OR system, glucose and urea detection systems on a base of such materials were proposed. The numerical modelling of biosensor made possible to determine several structural and kinetic parameters of the sensor constructed on a base of pyrroloquinoline quinone-containing glucose dehydrogenase.

Main publications:

Puida, M., Dabulytė-Bagdonavičienė, J., Ivanauskas, F., Razumas, V., Razumienė, J., Šakinytė, I. 2016. Glucose sensor based on nanostructured carbon electrode with immobilized PQQ-containing glucose dehydrogenase: construction, experimental study and mathematical modelling.  Nonlinear Analysis: Modelling and Control, vol. 21, no 5, p. 702–715.

Razumienė, J., Gurevičienė, V., Dagys, M., Šakinytė, I., Jonuška, A., Rimševičius, L., Marchenko, S., Soldatkin, A. 2016.  Development of multi-parameter analyser based on electrochemical urea biosensors and electrolyte electrodes for monitoring of hemodialysis patients. Proceedings of the 9th international joint conference on Biomedical Engineering Systems and Technologies (BIOSTEC 2016), vol. 1, p. 93–101.

Ivanauskas, F., Katauskis, P., Laurinavicius, V. 2016. Impact of convective transport and inert membrane on action of bio-catalytic filter. Journal of Mathematical Chemistry, vol. 54, no 6, p. 1221–1232.

The investigation of enzymes catalysed conversion of hydroxygroup containing substrates  

Conversion of N-hydroxy- compounds, alcohols and other substrates catalysed by oxidoreductases (laccases, peroxidases and quinoprotein dehydrogenases) was investigated. The catalytic activity of the enzymes in the process, influence of different factors (temperature, composition and pH of buffer solution) on it and final products of the reactions were determined.
Bioluminescence imaging experiments were carried out to characterize spatiotemporal patterns of self-organization of bioluminescent E. coli and its chemotaxis mutants in standard microtiter plates. An analysis of the effects of mutations shows that spatiotemporal patterns formed due to migration (swimming) of cells near three phase contact line are not related to the chemotaxis system of bacteria.

Main publication:

Jasevičius, R., Baronas R., Kačianauskas, R., Šimkus, R. 2015. Numerical modeling of bacterium-surface interaction by applying DEM. Book Series: Procedia Engineering, vol., p. 1408–1414.

Self-organization of chemotaxis mutants of E. coli

Bioluminescence imaging experiments were carried out to characterize spatiotemporal patterns of self-organization of bioluminescent E. coli and its chemotaxis mutants in standard microtiter plates. Analysis of the effects of mutations shows that spatiotemporal patterns formed due to migration (swimming) of cells near three phase contact line are not related to the chemotaxis system of bacteria.

National Research Projects

Research Council of Lithuania. Self-Organization of E. Coli and Their Mutants Near Three Phase Contact Line (MIP-001/2014). Dr. R. Šimkus. 2014–2016.

It is shown that patterns of bacterial self-organization are essentially dependent on the properties of mutants which characterize them as colloidal swimmers. In particular, the observed patterns are essentially dependent on the efficiency of proton translocation across membranes and the smoothness of the cell surface. These characteristics can be associated, respectively, with the surface activity and the phoretic mobility of the colloidal swimmer.

Main publication:

Šimkus, R., Meškienė, R., Ledas, Ž., Baronas, R., Meškys, R. 2016. Microtiter plate tests for segregation of bioluminescent bacteria. Luminescence, vol. 31, no 1, p. 127–134.

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:

Razumienė, J., Gurevičienė, V., Dagys, M., Šakinytė, I., Jonuška, A., Rimševičius, L., Marchenko, S., Soldatkin, A. 2016. Development of Multi-Parameter Analyser based on Electrochemical Urea Biosensors and Electrolyte Electrodes for Monitoring of Hemodialysis Patients. Proceedings of the 9th international joint conference on Biomedical Engineering Systems and Technologies (BIOSTEC 2016), vol. 1, p. 93–101.

Research Council of Lithuania. Bee Products Enriched with Plant Components, the Composition and Properties. (SVE-01/2012). Dr. B. Kurtinaitienė.
Beekeeping products conserved with quality honey were analysed. Various additives, as plant oils, algae powder, and royal jelly can modify biological activity of the mixes.  Bioanalytical oxidase activity measurement system was developed. Monitoring of the changes of mixture parameters via different storage conditions revealed a stabilizing influence of honey and additives on anti-oxidative properties, flavonoids composition and enzymes activity of the mixes. Investigation revealed the most advantageous to health ratio of saturated and unsaturated fatty acids optimized in these mixtures.

Main publications:

Čeksterytė, V., Kurtinaitienė, B., Venskutonis, P. R., Pukalskas, A., Kazernavičiūtė, R., Balžekas, J. 2016. Evaluation of antioxidant activity and flavonoid composition in differently preserved bee products. Czech Journal of Food Sciences, vol. 34, p. 133–142.

Čeksterytė, V., Navakauskienė, R., Treigytė, G., Jansen, E., Kurtinaitienė, B., Dabkevičienė, G., Balžekas, J. 2016. Lipodomics and proteomics in beebread and pollen. Bioscience, Biotechnology, and Biochemistry, vol. 80, No. 11, p. 2100–2108.

Kretavičius, J., Kurtinaitienė, B., Buckiūnienė, V. 2016. Influence of non-phenolic compounds of honey on antioxidant capacity. Veterinarija ir zootechnika (Veterinary Medicine and Zootechnics), vol. 73, no. 95, p. 82–87.

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. M. Dagys, partner – V. 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)                                                                                                                         
Malmo University (Sweeden)                                                                                                         
Institute of Molecular Biology and Genetics of the National Academy of Science of Ukraine     
CC Bioanalizės sistemos (Lithuania)                  
CC Ubique calculus (Lithuania)                                                                                                                           
CC Sentiero Baltic (Lithuania)

OTHER SCIENTIFIC ACTIVITIES

Prof. Habil. Dr. V. Laurinavičius –

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

Prof. Habil. Dr. V. Razumas –

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

Prof. Habil. Dr. J. Kulys –

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

DEPARTMENT OF BIOELECTROCHEMISTRY AND BIOSPECTROSCOPY

7 Salėtekio, LT-10257 Vilnius
Tel. 223 43 94
E-mail:
mailto:

Head – Dr. Gintaras Valinčius

STAFF

Chief research fellows: Dr. G. Valinčius, Habil.Dr. G. Niaura (part-time).
Senior research fellow: Dr. G. Preta.
Research fellow: Dr. M. Jankunec.
Junior research fellows: Dr. A. Bulavas, Dr. R. Budvytytė, Dr. B. Rakovska.
Specialists: T. Ragaliauskas, M. Talaikis.
Doctoral students: T. Penkauskas, J. Latynis, I. Aleknavičienė, K. Majauskaitė.

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 2016

Project Supported by University Budget

Spectroelectrochemical Studies of Biological Systems and Their Models. Dr. G. Valinčius. 2011–2018.

Tethered bilayer lipid membranes (tBLMs) consist of a lipid bilayer anchored by a mixed self-assembled monolayer (SAM) to a solid support. The water-induced structural changes were monitored by the isotope-edited SERS coupled with the first-principles calculations. The vibrational bands of deuterated 2-mercaptoethanol, which is widely used as surface back-filler, was performed. Two conformers: gauche and trans are dominating on the surface. Analysis of relative intensities revealed a decrease in relative amount of trans conformers after 72 h incubation of the SAM in water. At the same time an increase in the population of a long carbon chain molecular anchor (WC14) in the all-trans hydrocarbon chain conformation was obeserved by SERS. These structural changes suggest water-induced clustering of long-chain anchors, and conformational transition for short-chain thiols occurs simultaneousely.
Next aim was to develop biocathode for the molecular oxygen reduction in artificial nano-electrode systems. Spectroscopy evidence of the direct electron transfer from protein to the oxygen was provided by SERS.

Main publication:

Talaikis, M., Eicher-Lorka, O., Valincius, G., Niaura, G. 2016. Water-Iiduced structural changes in the membrane-anchoring monolayers revealed by isotope-edited SERS. Journal of Physical Chemistry C., vol. 120, p. 22489–22499.

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.

A series of new bifunctional cholesterol compounds for tethered bilayer membrane (tBLM) systems were synthesized and tested. Anchoring occurs through the insertion of the cholesterol moiety into the hydrophobic slab of the phospholipid layer, while the surface density of anchor molecules may be adjusted using disulfides terminated spacers. Another group of cholesterol derivatives described in this work contains either fluorescence probe or electroactive functional groups. We demonstrated the practical utility of these compounds for visualization of cholesterol extraction from and loading to tBLMs. We demonstrated that electroactive group containing cholesterol derivatives can be reconstituted either into vesicles or tBLMs. In both cases an electrochemical signal can be generated on electrodes from these probes.
The analysis of an electrochemical impedance response data of phospholipid biosensors in case of heterogeneous population of pore-forming toxins was performed.
In collaboration with parters from the NSIT center for Neutron Research (USA) and Swansea University (UK) we studied function and structure of one of the major virulence factors in cattle disease – bacterial piolysing which causes severe inflammation and animal infertility.

Main publications:

Eicher-Lorka, O., Charkova, T., Matijoška, A., Kuodis, Z., Urbelis, G., Penkauskas, T., Mickevicius, M., Bulovas, A., Valincius, G. 2016. Cholesterol-based tethers and markers for model membranes investigation. Chemistry and Physics of Lipids, vol. 195, p. 71–86;

Valincius, G., Mickevicius, M., Penkauskas, T., Jankunec, M. 2016. Electrochemical impedance spectroscopy of tethered bilayer membranes: an effect of heterogeneous distribution of defects in membranes.  Electrochimica acta, vol. 222, p. 904–613.

Preta, G., Jankunec, M., Heinrich, F., Griffin, S., Sheldon, I.M., Valincius, G. 2016. Tethered bilayer membranes as a complementary tool for functional and structural studies: the pyolysin case. Biochimica et Biophysica Acta-Biomembranes, vol. 1858, p. 2070–2080, doi: 10.1016/j.bbamem.2016.05.016.

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

Lithuanian University of Health Sciences, Institute of Neurosciences, Kaunas (Lithuania)
Centre for Physical Sciences and Technology, Institute of Chemistry, Vilnius (Lithuania)
University of Maryland, Institute for Biosciences and Biotechnology Research, Rockville, MD (USA)
NIST Center for Neutron Research, Gaithersburg, MD (USA)
Department of Biomedical Sciences, Faculty of Health and Society, Malmö University (Sweden)
Swansea University, Institute of Lifescience (United Kingdom)

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);
  • member of International Society of Electrochemistry;
  • expert of Research and Higher Education Monitoring and Analysis Centre (MOSTA).

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

7 Saulėtekio, LT-10257 Vilnius
Tel. 223 44 08
E-mail:

Head – Dr. Virginija Bukelskienė

STAFF

Senior research fellows: Dr. V. Bukelskienė, Dr. D. Baltriukienė.
Junior research fellow: R. Jarašienė-Burinskaja.
Senior assistants: I. Rinkūnaitė, A. Ščerbavičienė.
Assistants: D. Kulbienė, V. Untanienė, L. Vaškevičienė.
Doctoral students: M. Alksnė, E. Balčiūnas, E. Šimoliūnas.

RESEARCH INTERESTS

Laboratory animals                                                                                                                              
Cell culture                                                                                                                                              
Stem cells                                                                                                                                          
Tissues engineering

RESEARCH PROJECTS CARRIED OUT IN 2016

Project Supported by University Budget

Study of Cell Interactions with Scaffolds of Different Chemical Composition and Topography. Dr. V. Bukelskienė. 2014–2018.

The study is focussed on the evaluation of biocompatibility and proliferation activity of newly prepared bioglass-hydroxyapatite and polymer-hydroxyapatite composites of various formulations. In the investigations, primary different rat tissue (muscle, splint, dental pulp)-derived stem cell lines were used. The cells were grown on the 3D printed scaffolds. The best chemical formulation of the scaffolds was choosen which impact will be tested in more detailed cell signaling studies.

National Research Projects

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.

Numerous studies reported the presence of parvovirus B19 (PVB19) in the patients’ dilated cardiomyopathy (DCM) hearts implying that PVB19 might be causatively linked to the heart damage. However, the pathogenetic significance of PVB19 genomes in those patients is still a matter of debate. In our study, immunization of mice with PVB19 capsid protein VP1 unique region (VP1u) caused heart damage compatible with the DCM phenotype. In VP1u induced DCM, heart damage was focused around the vessels, thus in this study we evaluated the effect of PVB19 VP1u protein on endothelial cells (EC) in vitro. VP1u concentration used to mimic acute phase PVB19 infection levels were not toxic to EC, however they increased EC proliferation and migration potential. Cells treated with VP1u also demonstrated increased expression of proteins participating in immune and stress response implying EC activation. These results will help to elucidate the pathology associated with endothelial dysfunction with PV-B19 VP1u induced DCM.

Main publication:

Bogomolovas, J., Šimoliūnas, E., Rinkūnaitė, I., Smalinskaitė, L., Podkopajev, A., Bironaitė, D., Weis, C.-A., Marx, A., Bukelskienė, V., Gretz, N., Grabauskienė, V., Labeit, D., Labeit, S. 2016. A Novel murine model of parvovirus associated dilated cardiomyopathy induced by immunization with VP1-unique region of parvovirus B19. Biomed Research International Article ID 1627184, 9 p.

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.

By modulating the scaffold topography, it is possible to modify behavior of the cells maintained on these surfaces. The study was focused on the impact of biodegradable polylactic acid (PLA) scaffolds surface microstructurization to rat dental pulp stem cells (DPSC) adhesion, proliferation and differentiation. It was found that DPSC cell adhesion was not greatly affected by PLA surface topography; nevertheless, due to greater surface area for cells to settle wavy scaffolds, they were more favorable for DPSC to adhere. However, scaffolds surface topography influenced cells osteogenic differentiation capacity. It was found that microporous surface topography, with pores of 300 µm diameter, were more suitable for osteogenic differentiation.

Research Council of Lithuania. Science programme Healthy Aging project: Soft Tissue Engineering: from Cell to Artificial Tissue (No. SEN-13/2015). Dr. D. Baltriukienė. 2015–2018.  

PDMS (polydimethylsiloxane), an attractive material for tissue engineering applications, has some intrinsic drawbacks, like hydrophobicity, lack of biodegradability and poor suture support. To overcome some of these problems, we have synthesised several PDMS-based block copolymers and tested their biocompatibility. Some of these PDMS block copolymers showed varying degrees of swelling in aqueous media. Moreover, some materials expanded up to three times upon immersion in water. The observed swelling properties might prove promising in loading scaffolds with drugs or other bioactive molecules. As expected, both the chemical structure and polymerisation conditions had a strong influence on cellular metabolism.

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

Anticancer activity of two newly synthesized quinones was tested in three tumour-derived cell lines: human lung carcinoma (A-549), breast tumor (MCF-7) and promyelocytic leukemia cells (HL-60). The cells were treated with  naphtho[1′,2′:4,5]imidazo[1,2-a]pyridine-5,6-dione (NPDO) and 3-NO2-naphtho[1′,2′:4,5]imidazo[1,2-a]pyridine-5,6-dione (3-NO2-NPDO) and it was found that  both quinones caused mainly apoptotic cell death in all tested cell lines. In more detail studies, the role of these pro-apoptotic agents was assessed in cell signaling pathways: expression and activation levels of MAPKs (JNK, p38 and ERK) were evaluated.

Main publication:

Šarlauskas, J., Pečiukaitytė-Alksnė, M., Misevičienė, L., Marozienė, A. Polmickaitė, E., Staniulytė, Z., Čėnas, N., Anusevičius, Ž. 2016. Naphtho[1′,2′:4,5]imidazo[1,2-a]pyridine-5,6-diones: synthesis, enzymatic reduction and cytotoxic activity. Bioorganic & Medicinal Chemistry Letters, vol. 26, no. 2, p. 512–517.

Contractual Research

CC Centrinis Parkas. To Assess Feed Additives Toxicity by Using Laboratory Mice. Dr. V. Bukelskienė.
CC Valentis. Biological Evaluation of the Products. Dr. V. Bukelskienė.

AIN 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 Prodentum
CC Centrinis parkas

OTHER SCIENTIFIC ACTIVITIES

Dr. D. Baltriukienė –

Dr. V. Bukelskienė –

LABORATORY OF BIOORGANIC COMPOUNDS CHEMISTRY

12A Mokslininku, LT-08662 Vilnius
Tel. 272 90 58
E-mail:

Head – Dr. Regina Jančienė

STAFF

Senior research fellow: Dr. R. Jančienė.
Research fellows: Dr. A. Klimavičius, Dr. Z. Staniulytė.
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                                                                                               
Design and development of technology of chemical processes                                                            
Custom synthesis

RESEARCH PROJECTS CARRIED OUT IN 2016

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.

Dimesyltetraethylene glycol was synthesized by reaction of tetraethylene glycol with methansulphochloride. For substitution of mesyl groups by azido groups, several organic and inorganic azides were tested. The best results were obtained with sodium azide and α,ω-diazidotetraethylenglycol of high purity was synthesized. It was shown that triphenylphosphine was the most suitable for the synthesis of mono-amino-substituted product. Optimal reaction conditions for the synthesis of diazido and mono-amino derivatives were established in various volumes and the synthesis of ethylene glycol derivatives of various polimerization degree (n =4÷18) was performed.
Reaction of 5-benzyl or acetyl-substituted 1,5-benzodiazepin-2-one derivatives with ethylisocyanoacetate was performed under modified Wittig-Horner reaction conditions using potassium tret-butoxyde and diphenyl or diethylchlorophosphate. It was found that the main products of this reaction was not expected tricyclic compounds – imidazo[1,5-a][1,5]benzodiazepines, but nonciclized derivatives -  ethyl   5-[2-(acetyl or benzyl{2-[(diphenoxy- or diethoxyphosphoryl)amino]phenyl}amino)alkyl-1,3-oxsazole-4-carboxylate.
Structure of the new compounds was determined using 1H, 13C, 31P NMR, IR, mass and X-ray spectroscopy.

Main publication:

Šarlauskas, J., Pečiukaitytė-Alksnė, M., Misevičienė, L., Marozienė, A., Polmickaitė, E., Staniulytė, Z., Čėnas, N., Anusevičius, Ž. 2016. Naphtho[1′,2′:4,5]imidazo[1,2-a]pyridine-5,6-diones: Synthesis, enzymatic reduction and cytotoxic activity. Bioorganic & Medicinal Chemistry Letters, vol. 26, No. 2 , p. 512–517.

National Research Projects

Agency for Science, Innovation and Technology. National Program to Support R&D Contracts, invitation No. US02. Research in development of new methods for making alfa-amino omega-azido derivatives of polyethylene glycols;

Study of cyclization of p-cyano-o-nitrobenzyl-p-cyanophenylketone and the synthesis of experimental samples of DAPI;

Development of viable methods for the synthesis of various organic compounds and preparation of their experimental batches. 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

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

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

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

Ramidus AB (Sweden). Research in Development of New Methods for Making Alfa-Amino Omega-Azido Derivatives of Polyethylene Glycols. Dr. R. Jančienė.

Development of Viable Methods for the Synthesis of Various Organic Compounds and Preparation of their Experimental Batches. Synthon Chemicals Gmbh (Germany). Dr. R. Jančienė.

CC Ekorama. Optimization of Cultivation Conditions of Lipolytic Producents with the Aim to Select the Most Suitable Parameters of the Process. Dr. R. Jančienė.

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

Center 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

7 Sauletekio, LT-10257 Vilnius
Tel. 223 44 09
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

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 PROJECTS CARRIED OUT IN 2016

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.

Studies of molecular factors associated to senescence in cancer and stem cells.

Chemical agents’ capacity to induce cellular senescence was evaluated by testing gene expression analysis and by staining cells for SA-β-galactosidase activity determination. RT-qPCR analysis demonstrated elevated levels of p53, p21, Rb, ATM, HMGA gene expression after treatment with EGCG in leukemic NB4 cells. However, treatment with BIX-01294 increased only p21 gene expression. Further, SA-β-galactosidase staining supported observation of EGCG ability to induce cellular senescence but no SA-β-galactosidase cell staining was observed after treatment with BIX-01294. Western blot analysis was used for the evaluation both of protein modifications and expression in control and treated with EGCG or BIX-01294 leukemic cells. Increase of phospho-H2AX (Ser139) and phospho-ATM (Ser1981) modifications was determined after treatment with EGCG and BIX-01294 independently.
Human mesenchymal stem cells at passage 2 expressed specific cell surface (CD44, CD90, and CD105) and stemness (Oct4, Nanog, Sox2, and Rex1) markers. Within passages 8 and 10, senescent cultures exhibited typical morphological features, senescence-associated β-galactosidase activity, increased levels of p16, and decreased levels of miR-17 and miR-21 but showed differential expression of p21, p53, and ATM dependently on the onset of cell senescence.

Main publication:

Savickienė, J., Baronaitė, S., Zentelytė, A., Treigytė, G., Navakauskienė, R. 2016. Senescence-associated molecular and epigenetic alterations in mesenchymal stem cell cultures from amniotic fluid of normal and fetus-affected pregnancy. Stem Cells Int., 2016:2019498.

Studies of the regulatory mechanisms of cancer cells functioning revealed that different and opposite cell death regulating signaling pathways, which may counteract one another, are activated in non-small lung carcinoma cells during chemotherapeutic treatment. The involvement of various signal transduction pathways in cell death and survival processes as well as various therapeutic options directed to control of stem cells survival upon transplantation in patients with heart diseases were reviewed.

Main publications:

Stulpinas, A., Imbrasaitė, A., Krestnikova, N., Šarlauskas, J., Čėnas, N., Kalvelytė, A.V. 2016. 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, vol. 29, p. 26−39. https://dx.doi.org/10.1021/acs.chemrestox.5b00336 .

Abdelwahid, E., Kalvelyte, A. V., Stulpinas, A., de Carvalho, K. A. T., Guarita-Souza ,L. C., Foldes, G. 2016. Stem cell death and survival in heart regeneration and repair. Apoptosis, vol. 21, no. 3, p. 252– 268. https://dx.doi.org/10.1007/s10495-015-1203-4 .

National Research Projects

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 studies were performed in in vitro and in vivo models. We detected that combination of epigenetic agents at non-toxic doses; DZNep and Bel, with RA obtain in vitro differentiation effects in APL cell line NB4. We analyzed histone modifications in APL xenograft tumors and tissues in response to epigenetic agents-based treatment. The comparative data demonstrated higher levels of H3K4me3 and H3K9me3 and lower of H4Ac and H3K27me3 in APL xenograft tumors than in leukemic NB4 cells. These changes in histone marks may represent the status of cells or tissues of malignant and healthy organism.

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.

Human amniotic fluid derived mesenchymal stem cells (AF-MSCs) are obtained by amniocentesis a new stem cell source for regenerative medicine and therapy. These cells have multiple lineage differentiation potential towards osteogenic, adipogenic, myogenic, neurogenic, endothelial, and hepatic phenotypes in vitro and they even performed better than adult stem cells. Analysis of epigenetic changes revealed that levels of chromatin modifying enzymes such as Polycomb repressive complex 2 (PRC2) proteins (EZH2 and SUZ12), DNMT1, HDAC1, and HDAC2 were reduced after osteogenic differentiation of AF-MSCs.

Main publications:

Glemžaitė, M., Navakauskienė, R. 2016. Osteogenic differentiation of human amniotic fluid mesenchymal stem cells is determined by epigenetic changes. Stem Cells Int., 2016:6465307, doi: 10.1155/2016/6465307.

Valiulienė, G., Treigytė, G., Savickienė, J., Matuzevičius, D., Alksnė, M., Jarašienė-Burinskaja, R., Bukelskienė, V., Navakauskas, D., Navakauskienė, R. 2016. Histone modifications patterns in tissues and tumours from acute promyelocytic leukemia xenograft model in response to combined epigenetic therapy. Biomed Pharmacother, p. 79:62–70, doi: 10.1016/j.biopha.2016.01.044.

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

7 Saulėtekio, LT-10257 Vilnius
Tel. 223 43 86
E-mail:

Head – Dr. Rolandas Meškys

STAFF

Chief research fellow: Dr. R. Meškys.
Senior research fellows: Dr. V. Časaitė, Dr. L. Truncaitė, Dr. J. Urbonavičius.
Research fellows: Dr. R. Gasparavičiūtė, Dr. L. Kalinienė, Dr. L. Marcinkevičienė, Dr. R. Rutkienė, Dr. S. Povilonienė, Dr. J. Stankevičiūtė, Dr. D. Tauraitė, Dr. A. Zajančkauskaitė.
Junior research fellows: R. Meškienė, Dr. R. Stanislauskienė, Dr. S. Kutanovas, J. Vaitekūnas.
Doctoral students: A. Aučynaitė, J. Jakubovska, V. Petkevičius, M. Sadauskas, N. Urbelienė, E. Šimoliūnas (completed studies in 2016), A. Krikštaponis.
 
RESEARCH INTERESTS

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

RESEARCH PROJECTS CARRIED OUT IN 2016

Project Supported by University Budget

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

Novel microorganisms utilizing pyridine-2,3-dicarboxylic acid as a sole carbon source were identified as Rhodococcus sp. 23C1, Mycobacterium frederiksbergense 23ON and Cupriavidus campinensis 23K8. A pyridine-2,3-dicarboxylic acid dehydrogenase (quinolinate dehydrogenase) activity was detected in Rhodococcus sp. 23C1 and Mycobacterium frederiksbergense 23ON. The enzyme was partially purified from Rhodococcus sp. 23C1. Based on detection of nicotinic acid hydroxylase, 6-hydroxynicotinic acid hydroxylase and 2,5-dihydroxypyridine dioxygenase activities in the cell-free extract, a novel pathway of degradation of pyridine-2,3-dicarboxylic acid proceeding via formation of nicotinic acid was proposed for Cupriavidus campinensis 23K8. A bacterial isolate aerobically degrading pyridine-2,6-dicarboxylic acid was identified as Achromobacter sp. JS18. A novel pathway of pyridine-2,6-dicarboxylic acid degradation with 3-hydroxypicolinic acid as an intermediate was proposed for this bacteria. A pyridine-3,5-dicarboxylic acid-degrading bacterial isolate 35KP identified as Xanthobacter sp. was characterized for the first time. A phenazine methosulphate-dependent pyridine-3,5-dicarboxylate dehydrogenase activity was detected in the cell-free extract of Xanthobacter sp. 35KP.

Burkholderia sp. MAK1 (DSM102049), capable of using pyridin-2-ol as the sole carbon and energy source, was isolated from soil. Whole cells of Burkholderia sp. MAK1 were confirmed to possess a good ability to convert different pyridin-2-amines and pyridin-2-ones into their 5-hydroxy derivatives. Moreover, several methylpyridines as well as methylated pyrazines were converted to appropriate N-oxides. In conclusion, regioselective oxyfunctionalization of pyridine derivatives using whole cells of Burkholderia sp. MAK1 is a promising method for the preparation of various pyridin-5-ols and pyridin-N-oxides.

A novel virus vB_ArtM-ArV1 (ArV1) isolated from soil using Arthrobacter sp. 68b strain for phage propagation. Using bioinformatics approaches, 13 ArV1 structural genes were identified, including those coding for head, tail, tail fiber, and baseplate proteins. A further 6 ArV1 ORFs were annotated as putative structural proteins based on the results of proteomic analysis. Morphological characterization of ArV1 places this phage in the family Myoviridae. Comparative genome sequence analysis, however, indicates that ArV1 has more in common with siphoviruses than it does with any well-known myovirus.

Main publications:

Vaitekūnas, J., Gasparavičiūtė, R., Rutkienė, R., Tauraitė, D., Meškys, R. A. 2016. 2-hydroxypyridine catabolism pathway in Rhodococcus rhodochrous strain PY11.  Appl. Environ. Microbiol., vol. 82, p. 1264–1273, doi:10.1128/AEM.02975-15.

Stankevičiūtė, J., Vaitekūnas, J., Petkevičius, V., Gasparavičiūtė, R., Tauraitė, D., Meškys, R. 2016. Oxyfunctionalization of pyridine derivatives using whole cells of Burkholderia sp. MAK1. Sci. Rep., 39129, doi:10.1038/srep39129.

Ratautas, D., Laurynėnas, A., Dagys, M., Marcinkevičienė, L., Meškys, R., Kulys, J. 2016. High current, low redox potential mediatorless bioanode based on gold nanoparticles and glucose dehydrogenase from Ewingella Americana. Electrochim. Acta, vol. 199, p. 254–260. http://dx.doi.org/10.1016/j.electacta.2016.03.087.

National Research Projects

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 prodrugs and their activating enzymes applicable for cancer therapy. Novel enzymes active towards the modified nucleobases were isolated and tested as a prodrug activating catalysts.

Research Council of Lithuania. Screening and Analysis of Novel Enzymes Participating in Catabolism of Modified Uracil Base and Nucleosides (MIP-103/2015). Dr. J. Urbonavičius. 2015–2017.

Tricyclic wyosine derivatives are found at position 37 of eukaryotic and archaeal tRNAPhe. In Archaea, the intermediate imG-14 is targeted by three different enzymes that catalyze the formation of yW-86, imG, and imG2. We have suggested previously that a peculiar methyltransferase (aTrm5a/Taw22) likely catalyzes two distinct reactions: N1-methylation of guanosine to yield m1G; and C7-methylation of imG-14 to yield imG2. The recombinant aTrm5a/Taw22-like enzymes from both Pyrococcus abyssi and Nanoarchaeum equitans indeed possess such dual specificity. The substitutions of individual conservative amino acids of P. abyssi Taw22 (P260N, E173A, and R174A) have a differential effect on the formation of m1G/imG2, while replacement of R134, F165, E213, and P262 with alanine abolishes the formation of both derivatives of G37. The aTrm5a-type enzyme SSO2439 from Sulfolobus solfataricus, which has no N1-methyltransferase activity, exhibits C7-methyltransferase activity, thereby producing imG2 from imG-14. I was suggested renaming such aTrm5a methyltransferases as Taw21 to distinguish between monofunctional and bifunctional aTrm5a enzymes.

Main publications:

Urbonavičius, J., Rutkienė, R., Lopato, A., Tauraitė, D., Stankevičiūtė, J., Aučynaitė, A., Kaliniene, L., van Tilbeurgh, H., Meškys, R. 2016. Evolution of tRNAPhe: imG2 methyltransferases involved in the biosynthesis of wyosine derivatives in Archaea. RNA 2016, vol. 22, p. 1871–1883, doi: 10.1261/rna.057059.116.

Research Council of Lithuania. Agroecosystems Microbiota under Climate Change: Structure and Concordance Mechanisms (SIT-7/2015). Dr. E. Servienė (Nature Research Center), work package manager Dr. L. Kalinienė. 2015–2018.

For research on microbiota, metagenomic identification of microorganisms and viruses with subsequent phylogenetic analysis, viral genome cloning and sequencing, genome-wide knockout libraries for investigation of interacting gene products, transcriptomic analysis vie mRNA sequencing, proteomic analysis of viral replication complexes were employed. Aim of the application of these methods – exhaustive and detailed datasets, permitting bioinformatics analysis of global trends on the composition of target ecosystems as well as addressing exact reasons behind these trends. In such way, composition of microorganisms and viruses of cultural plant agroecosystems is described, and mechanisms governing this composition uncovered at the molecular level. This deep level of research wealth provides with unprecedent level of detail on impact of climate change on the structure of agroecosystem microbiota and trends for its future development.

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 was to investigate the initial steps of phage lytic infection by proteogenomic approaches. Three E. coli-specific bacteriophages, T4, FV3 and VpaE1, belonging to different genera (T4-like, rV5-like and Felix 01-like viruses) have been investigated. Total proteome of E. coli cells infected by phage FV3 revealed 45 phage proteins produced during first 15 minutes of infection and 1407 E. coli proteins. Early genes of T4, FV3 and VpaE1 have been cloned and expressed. During the purification steps of recombinant proteins several putative phage-bacterial protein complexes have been detected and examined. In addition, several methods suitable for construction of mutant phages have been optimized for the phages selected in this study.

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.

The main focus is the development of the innovative enzyme-screening techniques, involving the construction of tailored microorganisms and the synthesis of smart substrates.
A screening system for ADHs (or ketoreductases) based on oxygenase activity towards 3-acylindoles has been established by using E. coli strains harboring an auxiliary enzyme. Several metagenomic libraries were tested (approx. 300,000 clones) and 11 blue colonies forming clones were screened. A novel approach for esterases/lipase screening has been developed based on the pro-substrate cytidine derivative which is hydrolysed and then required for growth. The system was tested with 10 soil metagenomic libraries (27 clones selected; 14 sequenced).

Contractual Research

Analysis of Biodistribution of the Recombinant Therapeutic Proteins and their Aggregates Baxalta (Shire), Vienna, Austria. 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

7 Saulėtekio, LT-10257 Vilnius
Tel. 223 43 921, 223 43 782
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. L. Kosychova, Dr. A. Marozienė, Dr. G. Mikulskienė, Dr. V. Miliukienė, Dr. L. Misevičienė.
Doctoral students: E. Polmickaitė-Smirnova, 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 and atiparasitic 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 2016

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 mechanism and substrate specificity of two-electron reduction of quinones and two(four)-electron reduction of nitroaromatic compounds by E. coli oxygen-insensitive nitroreductase A (NfsA) was characterized. It was shown that: i) catalysis follows ping-pong mechanism with presumably rapid dissociation of NADP+ from the reduced enzyme form; ii) reduction of nitroaromatic compounds is almost by an order of magnitude higher than that of quinones possessing similar reduction energetics; iii) using the ‚stopped-flow‘ experiments, it has been shown that the oxidative half-reaction is the rate-limiting step of cvatalysis; and iv) the substrate specifity  of NfsA including the enhanced reacticity of 2-OH-1,4-naphthoquinones is similar to the class B nitroreductase of E. cloacae.

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 2016 were as follows: a) 12 new compounds of this group were synthesized; b) their single-and two-electron redox properties in reactions with cytochrome P-450 reductase and DT-diaphorase were determined, c) their cytotoxicity in 3 mammalian tumour cell lines was investigated; and d) 6 compounds were sent to NCI for testing their antitumour activity.

Main publication:

Sarlauskas, J., Peciukaityte-Alksne, M., Miseviciene, L., Maroziene, A., Polmickaite, E., Staniulyte, Z., Cenas, N., Anusevicius, Z. 2016. Naphtho[1',2':4,5]imidazo[1,2-a]-piridin-5,6-diones: synthesis and evaluation of their enzymatic reactivity and cytotoxic activity. Bioorg & Med Chem. Lett., vol. 26(2), p. 512–517, p. 1464–3405 (electronic).

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.

Some papers concerning the proteomic changes in RH1-resistant MH22a cells and expression of signalling proteins under the action of RH1 performed in the frame of this project appeared in 2016.

Main publications:

Ger, M.. Kaupinis, A., Nemeikaitė-Čėnienė, A., Šarlauskas, J., Cicėnas, J., Čėnas, N., Valius, M. 2016. Quantitative proteomic analysis of anticancer drug RH1 resistance in liver carcinoma. Biochimica et Biophysica Acta: Proteins and Proteomics, vol. 1864(2), p. 219–232.

Stulpinas, A., Imbrasaitė, A., Krestnikova, N., Šarlauskas, J., Čėnas, N., Kalvelytė, A.V. 2016. Study of bioreductive anticancer agent RH1-induced signals leading the wild-type p53-bearing lung cancer A549 cells to apoptosis. Chemical Research in Toxicology, vol. 29 (1), p. 26–39.

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 5 nitroheterocyclic compounds, testing of their antileishmanial and antiplasmodial activity.

Main publication:

Benitez, D., Madeiros, A., Fiestas, L., Panosso-Zenere, E.A., Maiwald, F., Prousis, K.C., Roussaki, M., Calageropoulou, T., Detsi, A., Jaeger, T., Šarlauskas, J., Peterlin, Masic, L., Kunick, K., Labadie, G.R., Flohe, L., Comini, M.A. 2016. Identification of novel chemical scaffolds inhibiting trypanothione synthetase from pathogenic trypanosomatids. PLOS Neglected Tropical Diseases, vol. 10 (4), p. 1–25 (e0004617).

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.

Main result was a paper characterizing kinetic parameters of flavocytochrome b2-catalyzed reduction of cytochrome c and ferricyanide in 2016.

Main publication:

Lesanavičius, M., Smutok, O., Valiauga, B., Marozienė, A., Gonchar, M., Krikštopaitis, K., Čėnas, N. 2016. Kinetic properties of flavocytochrome b2 from Hansenula polymorpha . Chemija, vol. 27 (2), p. 123–127.

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

7 Saulėtekio, LT-10257, Vilnius
Tel. 223 44 10
E-mail:

Head – Dr. Mindaugas Valius

STAFF

Senior research fellow: Dr. M. Valius.
Research fellows: Dr. A. Kaupinis, Dr. J. Cicenas.
Junior research fellow: Dr. M. Ger.
Doctoral students: A. Androšiūnaitė, D. Kučiauskas (completed studies in 2016), N. Dreižė.
Visiting scientists: Dr. V. Bastikar; P. Gupta.

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 2016

Project Supported by University Budget

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

Main publications:

Stankevicius, V., Vasauskas, G., Noreikiene, R., Kuodyte, K., Valius, M., Suziedelis, K. 2016. Extracellular matrix-dependent pathways in colorectal cancer cell lines reveal potential targets for anticancer therapies. Anticancer Res., vol. 36(9), p. 4559–67.

Urbonavicius, S., Urbonaviciene, G., Cicenas, J., Hoegh, A., Sandermann, A., Valius, M.  2016. A novel view to the pathogenesis of varicose veins: what proteins are talking? J Vasc Sur Ven Lymph Disord., vol. 4 (1), p. 145, doi: http://dx.doi.org/10.1016/j.jvsv.2015.10.031.

Kaupinis, A., Aitmanaite, L., Strepetkaite, D., Valius, M., Lazutka, J., Arbaciauskas, K. 2015. Proteomic and gene expression differences between post-diapause and subitaneous offspring phenotypes in the cyclic parthenogen Daphnia pulex. Hydrobiologia, 2016. DOI 10.1007/s10750-016-3057-3.

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.

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 highlighting the role of cancer stem-like cells in the drug resistance.

Main publications:

Ger, M., Kaupinis, A., Nemeikaite-Ceniene, A., Sarlauskas, J., Cicenas, J., Cenas, N., Valius, M. 2016. Quantitative proteomic analysis of anticancer drug RH1 resistance in liver carcinoma. Biochim Biophys Acta, 2016 Feb, vol. 1864(2), p. 219–32.

Nissinen, T., Näkki, S., Laakso, H., Kuciauskas, D., Kaupinis, A., Kettunen, M. I., Liimatainen, T., Hyvönen, M., Valius, M., Gröhn, O., Lehto, V. P. 2016. Tailored dual PEGylation of inorganic porous nanocarriers for extremely long blood circulation in vivo. ACS Appl Mater Interfaces, 2016 Dec 7, vol. 8(48), p. 32723–32731.

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 perform highthroughput quantitative proteomic and microRNomic analysis of the chemotherapy‐sensitive and ‐resistant colorectal cancer (CRC) 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 combinational chemotherapy by 5‐fluorouracil and oxaliplatin (FOLFOX).

Research Council of Lithuania: New Multifunctional Nanobiosensor for Early Pancreatic Cancer Diagnostics (Nr. SEN-16041). Project manager Prof. K. Strupas, work package manager Dr. M. Valius, 2015–2018.

In this project we will perform high-throughput protein biomarkers discovery using already collected as well as collected in the frame of this project patients' pancreatic material and samples of blood serum. The potential biomarkers will be validated in a larger group of patients. A novel multifunctional prototypical analytical system based on protein biomarkers detection with antibody-coated quantum dots and magnetic particles will be designed, fabricated and tested.

Main publication:

Sileikis, A., Petrulionis, M., Kurlinkus, B., Ger, M., Kaupinis, A., Cicenas, J., Valius, M., Strupas, K. 2016. Current role of proteomics in pancreatic cancer biomarkers research. Current Proteomics, vol. 13(1), p. 68–75.

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

University of Colorado, Denver (USA)
Swiss Institute of Bioinformatics, Geneva (Switzerland)
Aargus University, Aargus (Denmark)
University of North Carolina School of Medicine, Department of Farmacology, Chapel Hill (USA)
Lithuania National Cancer Center, Vilnius (Lithuania)
Vilnius University Hospital Santariskiu Klinikos, Vilnius (Lithuania)
Nation Center of Patology, Vilnius (Lithuania)

OTHER SCIENTIFIC ACTIVITIES

Dr. M. Valius –

  • editorial board member of the journal MAP Kinases.