91桃色

 7 Saul臈tekio av., LT-10257 Vilnius

Tel. 223 4435E-mail 

Director 鈥� Dr. Gintaras Valin膷ius

 

 

 

Institute of Biotechnology
Institute of Biochemistry
Institute of Biosciences

STAFF

77 teachers (incl. 60 holding research degree), 197 research fellows (incl. 142 holding research degree), 115 doctoral students.

 

INSTITUTE OF BIOTECHNOLOGY

7 Saul臈tekio, LT-10257 Vilnius
Tel. 223 4365
E-mail:

Director 鈥� Prof. Habil. Dr. Saulius Klima拧auskas

DEPARTMENTS OF THE INSTITUTE

Department of Protein - DNA Interactions
Department of Biological DNA Modification
Department of Eukaryote Gene Engineering
Sector of Microtechnologies
Department of Immunology and Cell Biology
Department of Biothermodynamics and Drug Design
Sector of Applied Biocatalysis
Department of Bioinformatics
Laboratory of Medical Epigenomics

RESEARCH AREAS

Structural biology and bioinformatics
Genomics, biomolecules and biotechnologies: fundamental and applied research

DOCTORAL DISSERTATIONS DEFENDED IN 2018

M. Norkien臈. Optimization of polyomavirus VP1 protein biosynthesis in S.cerevisiae cells and application of recombinant virus-like particles for serology.
M. Kazlauskien臈. Target RNA-dependent catalytic activities in a type III-A CRISPR-Cas system.
V. Kiseliovas. Development of microfluidic techniques for cancer and other biological research.
A. Merkys. Extraction and usage of crystallographic knowledge for refinement and validation of molecular models
P. Toliu拧is. Structure and function correlations within the atypical ATP-dependent restriction endonuclease CglI.
J. Lazutka. The development and evaluation of Schmallenberg virus detection systems.
A. Smirnov. Crystallographic studies of carbonic anhydrase isoforms and their complexes with inhibitors.
J. Kazokait臈. Investigation of human carbonic anhydrase VI and IX inhibitor efficacy and toxicity.
E. Zagorskait臈. Recognition of modified cytosine by methyl-directed restriction endonucleases.

MAIN CONFERENCES ORGANIZED IN 2018

12th international conference on Protein Stabilization (ProStab2018)
CRISPR 2018
XV international conference of the Lithuanian Biochemical Society
7th Amyloid Disease Annual Meeting (ADAM)
4th Symposium on Non-Globular Proteins

MAIN SCIENTIFIC ACHIEVEMENTS IN 2018

2018 Kavli Prize in nanosciences (Virginijus 艩ik拧nys) - for the invention of CRISPR-Cas9, a precise nanotool for editing DNA, causing a revolution in biology, agriculture, and medicine.
Lithuanian National Science award (Virginijus 艩ik拧nys, Giedrius Gasi奴nas, Tomas 艩ink奴nas, Tautvydas Karvelis) - for the collection of works CRISPR-Cas systems: from bacterial immunity to genome editing" (2011鈥�2016).
Lithuanian National Science award (Saulius Klima拧auskas) - for the collection of works Molecular tools for Epigenomics and RNomics (2011鈥�2016).

 
DEPARTMENT OF PROTEIN - DNA INTERACTIONS

7 Saul臈tekio, LT-10257 Vilnius
Tel. 223 4354
E-mail:

Head - Prof. Dr. Virginijus 艩ik拧nys

STAFF

Chief research fellows: Prof. Dr. V. 艩ik拧nys, Dr. S. Gra啪ulis, Dr. G. Sasnauskas, Dr. M. Zaremba, Dr. G. Tamulaitis.
Senior research fellows: Dr. G. Tamulaitien臈, Dr. E. Manakova, Dr. G. Gasi奴nas.
Research fellows: Dr. A. 艩ilanskas, Dr. T. 艩ink奴nas, Dr. T. Karvelis, Dr. G. Kostiuk.
Junior research fellows: Dr. P. Toliu拧is, I. Songailien臈, Dr. A. Merkys, Dr. E. Zagorskait臈.
Other researchers and technical staff: A. Tunevi膷, D. Smalakyt臈, E. Raginis, D. Tuminauskait臈, K. Pociut臈, R. 沤edaveinyt臈, J. Juozapaitis.
Doctoral students: A. Vaitkus, G. Drabavi膷ius, A. Grybauskas, G. Bigelyt臈, E. Golovinas, I. Mogila.

RESEARCH INTERESTS

Structural and molecular mechanisms of restriction enzymes

Bacterial antivirus defense systems Bacterial antivirus defense systems

Structural and molecular mechanisms of CRISPR-Cas machinery

CRISPR_Cas systems provide acquired immunity against viruses and plasmids. CRISPR represents a family of DNA repeats present in most bacterial and archaeal genomes. CRISPR loci usually consist of short and highly conserved DNA repeats, typically 21 to 48 bp, repeated from 2 to up to 250 times. The repeated sequences, typically specific to a given CRISPR locus, are interspaced by variable sequences of constant and similar length, called spacers, usually 20 to 58 bp. CRISPR repeat-spacer arrays are typically located in the direct vicinity of cas (CRISPR associated) genes. Cas genes constitute a large and heterogeneous gene family which encodes proteins that often carry functional nucleic-acid related domains such as nuclease, helicase, polymerase and nucleotide binding. The CRISPR/Cas system provides acquired resistance of the host cells against bacteriophages. In response to phage infection, some bacteria integrate new spacers that are derived from phage genomic sequences, which results in CRISPR-mediated phage resistance. Many mechanistic steps involved in invasive element recognition, novel repeat manufacturing, and spacer selection and integration into the CRISPR locus remain uncharacterized.

SELECTED PUBLICATIONS 2018

Mounet, N., Gibertini, M., Schwaller, P., Campi, D., Merkys, A., Marrazzo, A., Sohier, T., Castelli, I.E., Cepellotti, A., Pizzi, G., Marzari, N. 2018. Two-dimensional materials from high-throughput computational exfoliation of experimentally known compounds. Nature Nanotechnology, vol. 13, p. 246鈥�252,

Czapinska, H., Kowalska, M., Zagorskait臈, E., Manakova, E., Slyvka, A., Xu, S., Siksnys, V., Sasnauskas, G., Bochtler, M. 2018. Activity and structure of EcoKMcrA. Nucleic Acids Research, vol. 46, p. 9829鈥�9841,

Sasnauskas, G., Kauneckaite, K., Siksnys, V. 2018. Structural basis of DNA target recognition by the B3 domain of Arabidopsis epigenome reader VAL1. Nucleic Acids Research, vol. 46, p. 4316鈥�4324,

Toliusis, P., Tamulaitiene, G., Grigaitis, R., Tuminauskaite, D., Silanskas, A., Manakova, E., Venclovas, C., Szczelkun, M.D., Siksnys, V., Zaremba, M. 2018. The H-subunit of the restriction endonuclease CglI contains a prototype DEAD-Z1 helicase-like motor. Nucleic Acids Research, vol. 46, p. 2560鈥�2572,

Drabavicius, G., Sinkunas, T., Silanskas, A., Gasiunas, G., Venclovas, 膶., Siksnys, V. 2018. DnaQ exonuclease-like domain of Cas2 promotes spacer integration in a type I-E CRISPR-Cas system. EMBO Reports 19, e45543,

PATENTS 2018

Granted:
艩ik拧nys V., Gasi奴nas G., Karvelis T. RNA-directed DNA cleavage by the Cas9-crRNA complex. JP6423338B2. Publication date: November 14, 201.

Applications:
Fricke T., Bochtler M., Tamulaitis G., Kazlauskien臈 M., 艩ik拧nys V. Targeted RNA knockdown and knockout by type III-A Csm complexes. US20180105835A1. Publication date: April 19, 2018.

艩ik拧nys V., Gasi奴nas G., Karvelis T., Lubys A., 沤aliauskien臈 L., Glem啪ait臈 M., Smith A. RNA-directed DNA cleavage by the Cas9-crRNA complex. US20180187195A1. Publication date: August 05, 2018.

艩ik拧nys V., Kazlauskien臈 M., Kostiuk G., Tamulaitis G. Production of cyclic adenylates and their use as allosteric regulators. PCT/IB2018/053906. Filling date: May 31, 2018.

Jur臈nait臈-Urbanavi膷ien臈 S., Tamulaitis G. (2018) Method for cloning and expression of PfoI restriction endonuclease. US provisional patent aplication 62/650493. Filing date: March 30, 2018.

RESEARCH PROJECTS CARRIED OUT IN 2018

Projects Supported by University Budget

Structure-Function Relationship of Proteins and Protein Complexes. Prof. Dr. V. 艩ik拧nys. 2016鈥�2018.

Restriction and modification systems commonly act as the first line of intracellular defense against foreign DNA and function as sentries that guard bacterial cells against invasion by bacteriophage. R-M systems typically consist of two complementary enzymatic activities, namely restriction endonuclease (REase) and methyltransferase (MTase). In typical RM systems REase cuts foreign DNA but does not act on the host genome because target sites for REase are methylated by accompanying MTase. REases from 4000 bacteria species with nearly 330 differing specificities have been characterised. REases have now gained widespread application as indispensable tools for the in vitro manipulation and cloning of DNA. However, much less is known about how they achieve their function.
In the Laboratory of Protein-DNA Interactions we focus on the structural and molecular mechanisms of restriction enzymes. Among the questions being asked are: How do the restriction enzymes recognize the particular DNA sequence? What common structural principles exist among restriction enzymes that recognize related nucleotide sequences? How are the sequence recognition and catalysis coupled in the function of restriction enzymes? Answers to these questions are being sought using X-ray crystal structure determination of restriction enzyme-DNA complexes, site-directed mutageneses and biochemical studies to relate structure to function.

National Research Projects

Research Council of Lithuania/European Social Fund. Molecular Mechanisms of New Bacterial Antiviral Systems (No. 09.3.3-LMT-K-712-01-0126). Prof. Dr. V. 艩ik拧nys. 2018-2022.

Bacterial viruses, or bacteriophages, are bacterial parasites that employ the replication, transcription and translation machinery of the host cell to make new copies of the virus. They often kill bacteria when replication is completed. In order to survive bacteria built multiple defence barriers that interfere with nearly every step of virus life cycle. Different antiviral defence systems are clustered in the genome in the so-called 鈥渄efence islands鈥�. These defence islands, together with well-known antiviral defence systems, such as R-M and CRISPR-Cas systems, contain other putative antiviral defence systems of unknown molecular mechanism. The idea of the current project is that understanding of molecular mechanisms of novel antiviral defence systems in bacteria may pave the way for the development of new molecular technologies and tools. The major objective of the current project is to elucidate molecular mechanisms of two newly discovered bacterial antiviral defence systems, BREX and prokaryotic argonautes (pAgo). The major task of the project is to perform structural and functional characterization of protein components of the BREX and pAgo systems. We believe that the understanding of molecular mechanisms of these bacterial antiviral defence systems may pave the way the way for the development of new molecular tools.

Central Project Management Agency. Sequencing Center of DNA Double Stranded Breaks (No. 01.2.2-CPVA-K-703-02-0010). Dr. M. Zaremba. 2018鈥�2021.

The aim of the project is to develop and improve DNA double-strand break (DSB) detection technology. One of the most relevant applications of this method would be related to the genome (including human) editing and engineering, which is based on DSB introduction to the target site in the genome using programmable nucleases (homing endonuclease, ZF, TALE or CRISPR-Cas9 nucleases) and utilizing DNA repair systems of the cell. However, programmable nucleases are prone to cleave the DNA sites that are similar to the target sites, resulting in the chromosome rearrangements or mutations causing cell death or their transformation into cancer cells. In order to make genome editing technology safer it is crucial to utilize sensitive and reliable method for DSB detection to evaluate the specificity of a nuclease. Therefore, appropriate DSB detection technology allowing evaluation and selection of the most specific Cas9 or other nucleases for every particular case (including the gene therapy) will be developed during the project.

Research Council of Lithuania. Structure鈥怓unction Relationship of the B3 DNA Binding Domains (No. MIP 106/2015). Dr. G. Sasnauskas. 2015鈥�2018.

Approximately 10% of all transcription factors in the flowering plants contain one or several small (~110 amino acids) B3 DNA binding domains. The biochemical and structural data on B3 domains is very limited: DNA binding in vitro was demonstrated only for a few members of this family, and only one structure of the DNA-bound protein was solved. Our aim is to determine the relationship between the amino acid sequences (and the underlying structures) of the B3 domains and their function. To this end we will employ a combination of computational and biochemical characterization methods, site-specific mutagenesis, and X-ray crystallography.

Research Council of Lithuania. Research and Practical Applications of a Type I-F CRISPR-Cas System (No. S-MIP-17-47). Dr. G. Tamulaitien臈. 2017鈥�2020.

Prokaryotes are the most abundant cellular life form that is able not only to adapt to a variety of the physical conditions of life but also to the biological predators, called bacteriophages. To cope with the rapidly evolving phages, prokaryotes use various anti-virus systems. One of these is recently discovered defense system called CRISPR-Cas. According to composition of CRISPR-Cas effector complex and its mechanism these systems are classified into 6 types, which are then divided into subtypes. Elucidation of the molecular machinery of type II effector complex Cas9-sgRNR has enabled to adapt it as a powerful molecular tool, which allows precise editing of target DNA sequences. A practical potential of other CRISPR-Cas is not fully disclosed yet and requires studies of their molecular mechanisms. The object of the project is type I-F CRISPR-Cas from A. actinomycetemcomitans (Aa) bacteria that cause parodontitis. Effector complex of type I systems consist of 2 separate components: Cascade complex and Cas3 protein. Investigations of type I-E effector complex revealed that Cascade recognizes foreign DNA and binds it, and it is a signal to Cas3, which destroys DNA intruder. The composition of Cascade complex is slightly different between different subtypes of type I, and their properties should also vary. In case of type I-F system, details of the molecular mechanism of DNA degradation has not been studied yet; therefore, using in vivo and in vitro biochemical methods, we will seek to determine how the Cascade recognizes foreign DNA and how Cas3 destroys it. Furthermore, we will investigate the effect of DNA modifications on the system activity. These studies could help to find/create bacteriophages resistant to our system that could be used as a preventive measure against parodontitis. Using X-ray crystallography, we will try to figure out the mechanism of the CRISPR-Cas system at atomic level. Finally, we aim to add this system to the CRISPR-Cas molecular toolbox.

Research Council of Lithuania. Surface Nano-Structures for Mechanistic Studies of DNA - Protein Interaction at the Single-Molecule Level (No. S-MIP-17-59). Dr. E. Manakova. 2017鈥�2020.

Protein-nucleic acids (NA) interactions are playing a crucial role in the regulation of many cellular processes. Modern single-molecule fluorescence microscopy (SMFM) experimental approaches allow studying the real-time behavior of individual protein molecules during interaction with NA. However, these methods are technically challenging and not always successful. Also, due to labeling or surface effects, often it is challenging to collect enough data to prove statistical significance of effects measured during SM experiments. 鈥淒NA curtains鈥� is the next step in the development of the high-throughput SM methods. 鈥淒NA curtains鈥� are glass surface immobilized and in a predefined way distributed NA fragments, which are aligned horizontally with respect to the surface using the flow of the buffer solution. The method allows us to avoid complicated procedure of protein labeling - it is sufficient to conjugate it with the quantum dot (QD). Such a system allows studying many individual protein-NA interactions in a massively parallel manner. Potential of this new method for studying of protein - NA interactions is huge and therefore it is currently under intensive development. The main goal of the project is to create the novel platform for protein-NA interaction studies using SMFM. The platform is such that NA fragments are immobilized onto the glass surface, prepared by the proposed method, in an NA fragment density and arrangement controllable way. It also allows direct monitoring of interaction of the labeled protein with the immobilized NA fragments using an SMFM. Initially, we aim to test our platform with the relatively well characterized NA interacting proteins and later on to apply it for studies of less characterized objects. We expect that in the near future our developed platform will be relevant and broadly applied in other research groups, because it will allow revealing information (target search, interaction constants, etc.) on various protein - NA interactions, which is inaccessible or difficult to access in any other way.

Research Council of Lithuania. Structural and Functional Studies of Prokaryotic Argonaute Proteins (No. S-MIP-17-61). Dr. M. Zaremba. 2017鈥�2020.

Argonaute proteins (Agos) are widespread in all three domains of life (bacteria, archaea and eukaryotes). In eukaryotic organisms, Agos are the functional core of the RNA鈥恠ilencing machinery, which is critical for regulation of gene expression, silencing of mobile genome elements and defense against viruses. Defects in RNA interference (RNAi) machinery are associated with numerous major human pathologies, from metabolic disorders and viral infections to carcinogenesis. RNAi also has a broad therapeutic potential for various human diseases, such as infections and cancers. Despite the mechanistic and structural similarities between archaeal, bacterial and eukaryotic Agos, the biological function of bacterial and archaeal Agos remains elusive. The diversity of prokaryotic Agos structural organization and genomic context suggests a wide spectrum of functions and a variety of action mechanisms. For example, all eukaryotic Agos contain a PAZ domain responsible for binding of the 3鈥� end of the guide RNA strand, while bacterial and eukaryotic Agos are divided into two groups: with and without a PAZ domain. It is believed that most prokaryotic Agos containing a PAZ domain are active nucleases. In contrast, most PAZ-free Agos are found in operons with genes of putative nucleases or other effector proteins. It is therefore proposed that PAZ-free Agos might form functional complexes with these proteins. In the proposed project, we plan to elucidate the mechanism of action for an archaeal PAZ-free Argonaute protein. To this end we will employ a combination of biochemical experiments, single molecule FRET techniques and X-ray crystallography.

International Research Projects

H2020 Framework programme: Sonic Drilling Coupled with Automated Mineralogy and Chemistry On-Line-On-Mine-Real-Time (SOLSA) (No. 689868). Dr. S. Gra啪ulis. 2016鈥�2020.

The main goal of the SOLSA project is to create a novel system for identification of drill core characterisation using combined XRD, XRD and spectroscopic techniques. One of the main components of this new system is open databases of experimental structural data. The COD database will provide the collected open access descriptions of crystal structures that will enable rapid identification of sample composition in real time using the X-ray powder diffraction technique. The COD will also collect, preserve and disseminate data that will be determined by the SOLSA project. This data will be useful later for mineralogy, crystallography, geology and palaeontology, to name just a few areas of application. The SOLSA data will be unique since it will, for the first time, record comprehensive geospatial, stratigraphic, crystallographic and spectral information about the sample.

Research Council of Lithuania. Csm Effector Complex Labelling for Single Molecule FRET Experiments (No. APP-03/2016). Dr. G. Tamulaitis. 2016鈥�2018.

Recently we have showed that the Type III-A CRISPR-Cas system Csm effector complex from Streptococcus thermophilus (StCsm) cleaves RNA at specific sequences. This specificity can be easily reprogrammed by changing the crRNA molecule in the complex, which is a desirable function for biotechnology. Recently, we have determined the capability of this complex to cleave single-stranded DNA as well. The goal of this project is to study relationship between RNA and DNA cleavage dynamics and to engineer a minimal StCsm complex in order to develop it as a molecular tool suitable for precise RNA manipulations in vitro and gene regulation in vivo. We will employ a combination of biochemical characterization methods, X-ray crystallography and single molecule FRET assay. Single molecule experiments of labelled StCsm complex will be performed in collaboration with the project partners from Leipzig University.

Research Council of Lithuania. Research on Prediction of Environmental Change in the Baltic Sea Based on Comprehensive (Meta) Genomic Analysis of Microbial Viruses (No. LJB-17-001). Dr. G. Gasi奴nas. 2017鈥�2019.

Cyanobacteria blooms have significant influence on the Baltic Sea ecosystem functioning and services, and thus, human well-being and competitiveness of the region. The effective management of cyanobacteria blooms largely depends on the understanding of factors that drive cyanobacteria population dynamics. Cyanophages (viruses that infect cyanobacteria) play a key role in controlling structure and proliferation of host population, in particular, in eutrophic aquatic ecosystems. However, the Baltic Sea viruses, and their role in controlling cyanobacteria blooms remain litlle understood. Therefore, in this project we will perform the metagenomic analysis and quantitative assessment of the Baltic Sea virus community to reveal their contribution to cyanobacteria bloom development. The aim of the project is to investigate the impact of viruses on the cyanobacteria population dynamics in the Baltic Sea.

Research Council of Lithuania. CRISPR Tools for the Study of Embryonic Development in Zebrafish (No. S-LL-18-7). Dr. G. Tamulaitis. 2018鈥�2021.

Due to practical and ethical reasons, RNA silencing (not DNA knock-outs) is the preferred method in the studies of early development. The aim of this project is to develop novel RNA-silencing methods using the RNA-targeting CRISPR-Csm nucleases in vertebrate models, such as fish. Our preliminary experiments demonstrated that Csm nuclease pre-loaded with suitable crRNA can be used to target maternally expressed EGFP transcripts. During the project we are going to explore the possibility to use this tool to target endogenous transcripts and will quantify off-target effects using RNA sequencing techniques. Our next goal is to develop new tools for small targeted screens of (maternal) transcripts involved in early development that are not feasible using morpholinos, the current tool for RNA knockdown in zebrafish. The studies will be performed in collaboration with project partners from the International Institute of Molecular and Cell Biology in Warsaw.

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

UAB Thermo Fisher Scientific Baltics (Lithuania)
Bristol University (UK)
Leipzig University (Germany)
DANISCO (France)
DuPont (USA)

OTHER SCIENTIFIC ACTIVITIES

Prof. Dr. V. 艩ik拧nys 鈥�

• member of the Lithuanian Academy of Sciences;
• member of EMBO;
• member of EMBL council;
• member of EMBC council.

 

DEPARTMENT OF BIOLOGICAL DNA MODIFICATION

7 Saul臈tekio, LT-10257 Vilnius
Tel. 223 4350
E-mail:

Head - Prof. Habil. Dr. Saulius Klima拧auskas

STAFF

Chief research fellows: Prof. Habil. Dr. S. Klima拧auskas, Dr. G. Vilkaitis, Dr. V. Masevi膷ius.
Senior research fellows: Dr. E. Kriukien臈, Dr. R. Rakauskait臈, Dr. J. Gordevi膷ius.
Research fellows: Dr. M. Tomkuvien臈, Dr. V. Stankevi膷ius, Dr. V. Klimkevi膷ius.
Junior research fellows: G. Urbanavi膷i奴t臈, A. Osipenko, Z. Sta拧evskij, J. Li膷yt臈, M. Mickut臈, S. Gasiul臈.
Other researchers and technical staff: A. Ruk拧臈nait臈, D. Ikasalait臈, T. Asadauskas, M. Malik臈nas.
Doctoral students: P. Gibas, M. Narmont臈.

RESEARCH INTERESTS

Nucleic acids modification enzymes
Epigenome profiling
Biosynthesis of selenoproteins
Enzyme engineering

SELECTED PUBLICATIONS 2018

Mickut臈, M., Nainyt臈, M., Vasiliauskait臈, L., Plotnikova, A., Masevi膷ius, V., Klima拧auskas, S., Vilkaitis, G. 2018. Animal Hen1 2鈥�-O-methyltransferases as tools for 3鈥�-terminal functionalization and labelling of single-stranded RNAs. Nucleic Acids Research, vol. 46, e104,

Alexeeva, M., Guragain, P., T.sfahun, A. N., Tomkuvien臈, M., Arshad, A., Gerasimait臈, R., Ruk拧臈nait臈, A., Urbanavi膷i奴t臈, G., Bj酶r氓s, M., Laerdahl, J. K., Klungland, A., Klima拧auskas, S., Bjelland, S. 2018. Excision of the doubly methylated base N4,5-dimethylcytosine from DNA by Escherichia coli Nei and Fpg proteins. Philosophical Transactions of the Royal Society B: Biological Sciences, vol. 373, 20170337, .

Oh, G., Ebrahimi, S., Carlucci, M., Zhang, A., Nair, A., Groot, D.E., Labrie, V., Jia, P., Oh, E.S., Jeremian, R.H., Susic, M., Shrestha, T.C., Ralph, M.R., Gordevi膷ius, J., Koncevi膷ius, K., Petronis, A., 2018. Cytosine modifications exhibit circadian oscillations that are involved in epigenetic diversity and aging. Nature Communications, vol. 9, p. 644,

Gordevicius, J., Krisciunas, A., Groot, D.E., Yip, S.M., Susic, M., Kwan, A., Kustra, R., Joshua, A.M., Chi, K.N., Petronis, A., Oh, G., 2018. Cell-Free DNA Modification Dynamics in Abiraterone Acetate-Treated Prostate Cancer Patients. Clinical Cancer Research, vol. 24, p. 3317鈥�3324,

Skeberdyt臈, A., Sarapinien臈, I., Aleksander-Krasko, J., Stankevi膷ius, V., Su啪ied臈lis, K., Jarmalait臈, S., 2018. Dichloroacetate and salinomycin exert a synergistic cytotoxic effect in colorectal cancer cell lines. Scientific Reports, vol/ 8, 17744,

PATENTS 2018

Granted:
Klima拧auskas S., Rakauskait臈 R, Masevi膷ius V. Production of selenoproteins (selprot). EP3019194B1. Publication date: October, 17, 2018.

Klima拧auskas S., Sta拧evskij, Z, Kriukien臈 E. Nucleic acid production and sequence analysis. US9988673B2. Publication date: June 05, 2018.

Applications:
Klima拧auskas S., Vilkaitis G., Mickut臈 M. Analysis of single-stranded RNA. US20180251814A1. Publication date: Septemebr 06, 2018.

Klima拧auskas S., Vilkaitis G., Mickut臈 M. Analysis of single-stranded RNA. EP3271478A1. Publication date: January 24, 2018.

RESEARCH PROJECTS CARRIED OUT IN 2018

Projects Supported by University Budget

Nucleic Acids Modification Enzymes: Structure, Mechanisms of Action and Directed Engineering. Prof. Habil. Dr. S. Klima拧auskas. 2016鈥�2018.

In DNA, enzymatic methylation of nucleobases serves to expand the information content of the genome in organisms ranging from bacteria to mammals. Genomic DNA methylation is a key epigenetic regulatory mechanism in high eukaryotes. Aberrant DNA methylation correlates with a number of pediatric syndromes and cancer, or predisposes individuals to various other human diseases. However, research into the epigenetic misregulation and its diagnostics is hampered by the limitations of available analytical techniques. MicroRNAs and siRNAs are small non-coding double-stranded RNA molecules that control gene activity in a homology-dependent manner. Many microRNAs have well-defined developmental and tissue-specific expression pattern, but a great number of microRNAs and their roles are still unknown. We aim to develop new approaches to genome-wide profiling of DNA and RNA methylation for epigenome studies and improved diagnostics.

National Research Projects

Research Council of Lithuania/European Social Fund. Single Molecule TOP-Seq 鈥� an Innovative Technological Platorm for Early Non-Invasive Diagnostics of Cancer and Other Epigenetic Disorders (No. 09.3.3-LMT-K-712-01-0041). Dr. E. Kriukien臈. 2018鈥�2022.

Cancer-specific mortality from most types of solid tumors has barely decreased in decades, despite an exponential increase in our knowledge about cancer pathogenesis and significant investments in the development of effective treatments. Liquid biopsies are non-invasive blood tests that detect cell-free circulating DNA (cfDNA) fragments that are shed into the bloodstream from a primary tumor. We offer a novel strategy for non-invasive diagnostics of epigenetic disorders including cancer. It will combine the unique advantages offered by droplet microfluidics technology and targeted analysis of epigenetic DNA modification. The resulting integrated analytical platform for analysis of cfDNA at a single molecule level will lead to accurate determination of a malignant tissue in cfDNA.

Research Council of Lithuania. Identification and Analysis of Small Non-Coding RNAs of Gram-Positive Lactic Acids Bacteria Involved in Resistance to Antibacterial Agents (No. MIP 59/2015). Dr. G. Vilkaitis. 2015鈥�2018.

During this project we will try to identify and characterize Lactococcus lactis and Lactobacillus casei small non-coding RNAs responsible for their resistance to lysozyme, beta-lactam and glycopeptide antibiotics. For this, we will apply functional-genetic and next-generation sequencing based analysis. In order to overcome the most common sequencing biases we will try to create and implement the new bacterial sRNA specific bias-reducing method for RNA sequencing library preparation.

Research Council of Lithuania. Age-Related Remodelling of Aorta and Dilatative Pathology of Ascending Aorta: Search for Epigenetic Biomarkers (No. SEN-05/2016). Dr. G. Vilkaitis. 2016鈥�2018.

Ageing is a non-modifiable risk factor for development of cardiovascular diseases but the underlying molecular remodelling mechanisms of ageing vessels has not been investigated sufficiently yet. In recent years a breakthrough in epigenetic studies of mechanisms involved in medial smooth muscle cells phenotypic changes, especially in the field of non-coding RNAs was demonstrated. The aim of this project is to profile selected non-coding RNAs involved in morphogenesis of ascending aorta aneurysm and in age-related aortic remodelling. Clinical, histomorphometric, and epigenetic studies will be performed to evaluate the clinical feasibility of these ncRNAs as biomarkers for ascending aorta aneurysm diagnostics and prognosis.

Research Council of Lithuania. Photosensitive Handles for Selective Manipulations of Biosynthetic Proteins (No. S-MIP-17-57). Prof. S. Klima拧auskas. 2017鈥�2020.

Photochemical transformations enable exquisite spatio-temporal control over biochemical processes, however, methods for reliable site-selective modification of proteins with biocompatible photo-sensitive high affinity reporters are lacking. The objective of this project is to create a high affinity binder specific to biosynthetically incorporated chemically modified amino acid residues carrying a photolytically removable caging group. We will utilize genetically encoded incorporation and chemical modification to synthesize proteins with photocaged cysteine or selenocysteine residues for subsequent production in a murine system of monoclonal antibodies against the photoremovable 4,5-dimethoxy-2-nitrobenzyl (DMNB) tag. Employing the produced antibodies, a general method for light-controlled protein affinity enrichment of photocaged target proteins from complex biological mixtures will be developed.

Research Council of Lithuania. A Technology for Single-Cell Analysis of Genomic DNA Modification. Neuroblastoma Epigenetic Heterogeneity (No. S-MIP-17-58). Dr. E. Kriukien臈. 2017鈥�2020.

Neuroblastoma is a malignancy of the developing nervous system that is characterized by extreme clinical heterogeneity. For high-risk neuroblastoma patients, the prospect of long-term survival is dismal despite intensive multimodal therapy. Varying cellular composition detected at the same stages of neuroblastoma tumors might influence unexpected disease progression, which prevents accurate assessment of disease prognosis. DNA methylation and demethylation of cytosines (mC) in the context of CG sites is a major epigenetic regulatory mechanism implicated in tumorogenenesis. During cancer development and progression, two epigenetic abnormalities are commonly observed: global hypomethylation and localized hypermethylation of specific promoters. Due to high heterogeneity of neuroblastoma cells it is unclear how changes in DNA modification define the tumorigenicity of different neuroblastoma cell types. Within the time-frame of the project, we will develop a new method for single-cell analysis of genomic hmC/unmodified CG profiles. We will employ our recently elaborated unique and economical approach for targeted sequencing of covalently labeled unmodified CG sites, TOP-seq with the most recent advance in single-cell techniques, droplet microfluidics. The new technology will be used to explore the epigenetic heterogeneity of neuroblastoma.

International Research Projects

ERC Advanced Grant. Epitrack - Single-Cell Temporal Tracking of Epigenetic DNA Marks (ERC-2016-ADG/742654). Prof. S. Klima拧auskas. 2017鈥�2022.

DNA methylation is a prevalent epigenetic modification in mammals, which is brought about by enzymatic transfer of methyl groups from the S-adenosylmethionine (SAM) cofactor by three known DNA methyltransferases (DNMTs). The most dramatic epigenomic reprogramming in mammalian development occurs after fertilization, whereby a global loss of DNA methylation is followed by massive reinstatement of new methylation patterns, different for each cell type. Although DNA methylation has been extensively investigated, key mechanistic aspects of these fascinating events remain obscure. The goal of this proposal is to bridge the gap in our understanding of how the genomic methylation patterns are established and how they govern cell plasticity and variability during differentiation and development. These questions could only be answered by precise determination of where and when methylation marks are deposited by the individual DNMTs, and how these methylation marks affect gene expression. To achieve this ambitious goal, we will metabolically engineer mouse cells to permit SAM analog-based chemical pulse-tagging of their methylation sites in vivo. We will then advance profiling of DNA modifications to the single cell level via innovative integration of microdroplet-based barcoding, precise genomic mapping and super-resolution imaging. Using this unique experimental system we will determine, with unprecedented detail and throughput, the dynamics and variability of DNA methylation and gene expression patterns during differentiation of mouse embryonic cells to neural and other lineages.

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

Centre for Addiction and Mental Health, Toronto (Canada)
Cambridge University, Cambridge (U.K.)
University of Paul Sabatier, Toulouse (France)
University of Stavanger, Stavanger (Norway)
International Institute of Molecular and Cell Biology, Warsaw (Poland
University of Southern California, Los Angeles (USA
RIKEN Yokohama (Japan)
INRA (France)
Tartu University (Estonia)
University of Stuttgart (Germany)
Stanford University (USA)
IMB Mainz (Germany)

OTHER SCIENTIFIC ACTIVITIES

Prof. Habil. Dr. S. Klima拧auskas 鈥�

• member/ chairman of the Biology division, the Lithuanian Academy of Sciences;
• Fellow of the Royal Society of Chemistry;
• EMBO member;
• editorial advisory board member of the Open Life Sciences,
• management committee member, COST actions CM1303, CM1406;
• member of the advisory expert group, Strategic Council on Scientific Research, Technological Development and Innovations of Lithuania.

 

DEPARTMENT OF EUKARYOTE GENETIC ENGINEERING

7 Saul臈tekio, LT-10257 Vilnius
Tel. 223 4421
E-mail:

Head - Dr. Rasa Petraityt臈-Burneikien臈

STAFF

Chief research fellows: Prof. Habil. Dr. K. Sasnauskas, Dr. A. Gedvilait臈, Dr. R. Slibinskas.
Senior research fellows: Dr. R. Petraityt臈-Burneikien臈, Dr. A. Ra啪anskien臈, Dr. G. 沤virblis, Dr. E. 膶iplys.
Research fellows: Dr. V. Kazanavi膷i奴t臈, Dr. R. Ra啪anskas, Dr. D. 沤iogien臈, Dr. A. Bulavait臈, Dr. P.L. Tamo拧i奴nas, Dr. M. Norkien臈, Dr. M. Zaveckas.
Junior research fellows: Dr. A. Abraitien臈, Dr. J. Lazutka, R. Zinkevi膷i奴t臈.
Other researchers and technical staff: E. Rudokien臈, R. Vorobjovien臈, G. Vercholamova, O. Jan膷evskaja, D. Jaskyt臈, A. 艩ileikait臈, K. Ju拧kait臈.
Doctoral students: E. Bak奴nait臈, N. Macijauskait臈, G. Mickien臈, 艩. Pa拧kevi膷ius, 沤. Dapk奴nas, E. 沤itkus, A. 艩pakova, M. Valavi膷i奴t臈, J. Rainyt臈.

RESEARCH INTERESTS

Synthesis of recombinant proteins
Molecular tools for diagnostics
Investigation and characterization of new polyomaviruses, parvoviruses, paramyxoviruses and hantaviruses
Improvement of expression systems and yeast genetic background for efficient production of recombinant viral proteins in yeast cells
Cell signaling regulation in Arabidopsis
Functions of PP2C phosphatases

SELECTED PUBLICATIONS 2018

Simanavicius, M., Tamosiunas, P.L., Petraityte-Burneikiene, R., Johne, R., Ulrich, R.G., Zvirbliene, A., Kucinskaite-Kodze, I. 2018. Generation in yeast and antigenic characterization of hepatitis E virus capsid protein virus-like particles. Applied Microbiology and Biotechnology, vol. 102, p. 185鈥�198,

Zaveckas, M., Goda, K., Ziogiene, D., Gedvilaite, A. 2018. Purification of recombinant trichodysplasia spinulosa-associated polyomavirus VP1-derived virus-like particles using chromatographic techniques. Journal of Chromatography B, vol. 1090, p. 7鈥�13,

Janulaitiene, M., Gegzna, V., Baranauskiene, L., Bulavait臈, A., Simanavicius, M., Pleckaityte, M. 2018. Phenotypic characterization of Gardnerella vaginalis subgroups suggests differences in their virulence potential. PLoS One, vol. 13, e0200625,

Simanavicius, M., Juskaite, K., Verbickaite, A., Jasiulionis, M., Tamosiunas, P.L., Petraityte-Burneikiene, R., Zvirbliene, A., Ulrich, R.G., Kucinskaite-Kodze, I. 2018. Detection of rat hepatitis E virus, but not human pathogenic hepatitis E virus genotype 1-4 infections in wild rats from Lithuania. Veterinary Microbiology, vol. 221, p. 129鈥�133,

艩ul膷ius, S., Mazur-Marzec, H., Vitonyt臈, I., Kvederavi膷i奴t臈, K., Kuznecova, J., 艩imoli奴nas, E., Holmfeldt, K. 2018. Insights into cyanophage-mediated dynamics of nodularin and other non-ribosomal peptides in Nodularia spumigena. Harmful Algae, vol. 78, p. 69鈥�74,

RESEARCH PROJECTS CARRIED OUT IN 2018

National Research Projects

Research Council of Lithuania/European Social Fund. New technologies for development of recombinant allergens (No. 01.2.2-LMT-K-718-01-0008). Dr. G. 沤virblis. 2018鈥�2022.

The project is in line with EU Smart Specialization program and its priority 2.1. Molecular Technologies for Medicine and Biopharmaceutics. It is dedicated for development of advanced molecular technologies for allergy diagnosis, immunotherapy and universal platform of expression and purification of recombinant protein allergens. Final project goal is to prepare a open-access collection (bank) of recombinant allergens consisting of well-characterized recombinant allergens and their strains-producers adapted to the effective biosynthesis in the most relevant hosts such as bacteria, yeast, mammalian and plant cell cultures. The project is aimed at selecting optimal biosynthesis conditions for specific protein allergens, ensure their high level of expression, efficient purification, their proper antigenicity and similarity to the natural allergens.

Research Council of Lithuania. Investigation of Synthesis Regulation of Proteins Associated with Alzheimer Disease Development (No. SEN-05/2015). Prof. Habil. Dr. K. Sasnauskas. 2015鈥�2018.

Recently was shown that the majority of eukaryotic gene has a surprisingly large variety of protein translation start point in noncoding 5鈥�-end of mRNA. About 50% of annotated in gene bank human mRNA have at least several additional open reading frames (ORF) in non-coding 5鈥�-end of mRNA. The project goal is to create immunochemical, antibody-based methods that allow to test small ORF encoded polypeptides. Such methods will help to identify small polypeptides and determine role of these peptides in the regulation of biosynthesis of AD related proteins and provide new opportunities for disease prevention and early diagnosis.

Research Council of Lithuania. Investigation of K.Lactis Mutations Conferring Enhanced Secretion Phenotype and Generation of Yeast Strains for Supersecretion of Recombinant Proteins (No. S-MIP-17-88). Dr. A. Gedvilait臈. 2017鈥�2020.

Yeast, especially Saccharomyces cerevisiae, serves as an important model eukaryote for many fundamental studies and as hosts for recombinant protein production. Kluyveromyces lactis, a close relative of S. cerevisiae, is very attractive for biotechnological processes as has the broader metabolic diversity and significant advantages in the production of certain secreted proteins than baker鈥檚 yeast. Through detailed knowledge of the secretion pathway - an essential process for living organisms - and engineering, it has become possible to improve the secretion yield and efficiency of some proteins in engineered S. cerevisiae. Yet despite all advantages, heterologous protein secretion in yeast, in many instances, is far from optimal. This can be explained by the complexity of protein processing and secretion pathways and needs for further studies. The aim of the project is identification and characterization of K. lactis gene and its mutation/s conferring the super-secretion phenotype and application of acquired knowledge for generation of new yeast super-secretion strains.

International Research Projects

Research Council of Lithuania. Studying of Human Parvovirus B19, Bocavirus and Parvovirus 4 Involvement In Inflammatory Neurological Diseases Using Interdisciplinary Approach (No. TAP LLT-3/2017). Dr. R. Petraityt臈-Burneikien臈. 2017鈥�2019.

Meningitis, encephalopathy and encephalitis are serious diseases of the central nervous system that often are caused by a viral infection, but in most cases their etiology remains unknown. Parvovirus human parvovirus B19, human bocavirus and human parvovirus 4 are members of Parvoviridae family. There are hypothesis of B19 as a cause of extremely wide range of clinical manifestations including neurological diseases. The aim of this project is to study the involvement of human parvoviruses on etiopathogenesis of meningitis and encephalitis/meningoencephalitis with unknown etiology and unspecified encephalopathy in adult population as well as to develop rapid serodiagnostic and molecular diagnosis detection tools for parvovirus infection using interdisciplinary approach.

Contractual Research

Recombinant Viral Proteins. Abcam Ltd, London, UK. Dr. G. 沤virblis, Dr. R. Petraityt臈-Burneikien臈.

Recombinant Viral Proteins. Arc Dia International Oy Ltd, Finland. Dr. R. Petraityt臈-Burneikien臈.

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

Institute for Novel and Emerging Infectious Diseases (Germany)
Department of Virology, University of Freiburg (Germany)
Friedrich-Loeffler-Institut Bundesforschungsinstitut f眉r Tiergesundheit, Federal Research Institute for Animal Health OIE Collaborating Centre for Zoonoses in Europe (Germany)
Max Planck Institute for Molecular Plant Physiology (Germany)
Robert Koch-Institut (Germany)
Institute of Virology, Slovak Academy of Sciences (Slovakia)
A.Kirchenstein Institute of Microbiology and Virology, Riga Stradins University (Latvia)
Department of Medical Research, Mackay Memorial Hospital, (Taiwan)

OTHER SCIENTIFIC ACTIVITIES

Prof. Habil. Dr. K. Sasnauskas 鈥�

• member of the Lithuanian Academy of Sciences.

 

SECTOR OF MICROTECHNOLOGIES

7 Saul臈tekio, LT-10257 Vilnius
Tel. 223 4356
E-mail:

Head - Dr. Linas Ma啪utis

STAFF

Chief research fellow: Dr. L. Ma啪utis.
Research fellow: Dr. K. Leonavi膷ius.
Junior research fellows: D. Ku膷iauskas, J. Nainys, V. Milkus, R. 沤ilionis.
Other researchers and technical staff: L. Karpus, J. Ritmejeris, R. Kisielius, I. Ma啪elis, E. Gegevi膷ius.
Doctoral students: J. Nainys, G. Stonyt臈, K. Goda.

RESEARCH INTERESTS

Droplet microfluidics
Single-cell transcriptomics, genomics and epigenomics
Directed evolution of enzymes
Antibody screening

SELECTED PUBLICATIONS 2018

Plasschaert, L.W., 沤ilionis, R., Choo-Wing, R., Savova, V., Knehr, J., Roma, G., Klein, A.M., Jaffe, A.B. 2018. A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte. Nature, vol. 560, p. 377鈥�381,
https://doi.org/10.1038/s41586-018-0394-6.

Azizi, E., Carr, A.J., Plitas, G., Cornish, A.E., Konopacki, C., Prabhakaran, S., Nainys, J., Wu, K., Kiseliovas, V., Setty, M., Choi, K., Fromme, R.M., Dao, P., McKenney, P.T., Wasti, R.C., Kadaveru, K., Mazutis, L., Rudensky, A.Y., Pe鈥檈r, D. 2018. Single-cell map of diverse immune phenotypes in the breast tumor microenvironment. Cell, vol. 174, p. 1293鈥�1308.e36,

van Dijk, D., Sharma, R., Nainys, J., Yim, K., Kathail, P., Carr, A.J., Burdziak, C., Moon, K.R., Chaffer, C.L., Pattabiraman, D., Bierie, B., Mazutis, L., Wolf, G., Krishnaswamy, S., Pe鈥檈r, D. 2018. Recovering gene interactions from single-cell data using data diffusion. Cell, vol. 174, p. 716鈥�729.e27,

Zemmour, D., Zilionis, R., Kiner, E., Klein, A.M., Mathis, D., Benoist, C. 2018. Single-cell gene expression reveals a landscape of regulatory T cell phenotypes shaped by the TCR. Nature Immunology, vol. 19, p. 291鈥�301,

Hrvatin, S., Hochbaum, D.R., Nagy, M.A., Cicconet, M., Robertson, K., Cheadle, L., Zilionis, R., Ratner, A., Borges-Monroy, R., Klein, A.M., Sabatini, B.L., Greenberg, M.E. 2018. Single-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex. Nature Neuroscience, vol. 21, p. 120鈥�129,

PATENTS 2018

Granted:
Italiano J., Ma啪utis L., Thon J.N., Weitz D.A. System and method for a biomimetic fluid processing. JP6429794B2. Publication date: November 28, 2018.

Applications:
Weitz, D.A., Klein, A.M., Akartuna, I., Ma啪utis, L., Kirschner, W.M. Systems and methods for barcoding nucleic acids. US20180071705A1. Publication date: March 15, 2018. US20180304222A1. Publication date: October 25, 2018.

Italiano, J., Ma啪utis, L., Thon, J.N., Weitz, D.A. System and method for a biomimetic fluid processing. US20180021780A1. Publication date: January 25, 2018.

Ma啪utis, L., Stonyt臈, G., Kiseliovas, V., 沤ilionis, R., Janulaitis, A., Galinis, R., Studer, S. Hilvert D. System and method for synthesis of dna particles and use thereof. EP3402594A2. Publication date: November 21, 2018.

RESEARCH PROJECTS CARRIED OUT IN 2018

National Research Projects

Research Council of Lithuania/European Social Fund. Microfluidic Technologies for Single-Cell Geno- and Fenotyping Research (No. 09.3.3-LMT-K-712-01-0056). Dr. L. Ma啪utis 2018鈥�2021.

There is no doubt that advances of genomics technologies over the last decade have fundamentally altered our understanding of human biology and keeps affecting all branches of life sciences. However, until very recently most of the techniques used in the biological research have utilized homogenized tissues or mixtures of cells thus resulting in an 鈥渁verage鈥� genotype (or phenotype) that does not recapitulate the true diversity of cells or their biological differences. Cellular heterogeneity is particularly relevant in biological systems where individual cells show profound physiological differences such as immune system or cancer. By enabling the analysis of tens of thousands of single-cells in a massively parallel fashion droplet microfluidics technology has created a breakthrough in biological and biomedical sciences. In this project, we will harness the latest advances in droplet microfluidics and will establish a platform enabling quantitative analysis of phenotype-genotype linkage at single-cell level and do so in a high-throughput manner. Most of our research efforts will be directed towards immune cells producing therapeutic antibodies (phenotype) and recovery of the antibody-encoding sequences at single-cell level. We will apply developed platform to better understand the generation of antibody diversity by immune system, while the platform itself will likely to find a myriad of application in cell biology research, early disease diagnostics or directed evolution amongst others.

International Research Projects

H2020 FRAMEWORK PROGRAMME: Directed EVOlution in DROPS (H2020-MSCA-ITN-2018 Grant agreement ID: 813786). Dr. L. Ma啪utis. 2018鈥�2022.

Natural evolution is a powerful process that has given rise to the functionally diverse set of proteins present in all living systems. However, natural evolution has driven the optimisation of enzymes subjected to living functions of microorganisms, according to ill-defined and fluctuating external conditions and is not suitable for industrial processes since it lacks of control of selection pressure. In EVOdrops, we will use directed evolution to overcome these limitations. It is a synthetic, man-made approach of evolution, aiming at improving living systems based on predefined needs, controlling the external selection pressure. While natural evolution took billions of years to optimise macromolecules, directed evolution 鈥� to be efficient in an industrial process 鈥� requires both the generation of genetic diversity and ultra-high throughput screening capabilities to recover the variants of interest. We will develop and optimise these tools using the ground-breaking potential of droplet-based microfluidics for high-throughput experimentation and the fine control of gene library construction. EVOdrops, a European training network, will bring together the leading research scientists, laboratories and industries in Europe with outstanding expertise in protein engineering and microfluidics.

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

Harvard Medical School (USA)
Harvard University, School of Engineering and Applied Sciences (USA)
Columbia University (USA)
CALTECH (USA)
ETH Zurich (Switzerland)

OTHER SCIENTIFIC ACTIVITIES

L. Ma啪utis 鈥�

• participant of Human Cell Atlas and Human Tumor Atlas international projects;
• Start-up 鈥淒roplet Genomics鈥�, Vilnius, LT;
• Start-up 鈥淧latelet Biogenesis鈥� Inc. Boston, MA, USA.

 

DEPARTMENT OF IMMUNOLOGY AND CELL BIOLOGY

7 Saul臈tekio, LT-10257 Vilnius
Tel. 223 4360
E-mail:

Head - Dr. Aurelija 沤virblien臈

STAFF

Chief research fellows: Dr. A. 沤virblien臈, Dr. M. Ple膷kaityt臈.
Senior research fellows: Dr. I. Ku膷inskait臈-Kodz臈, Dr. A. Kanopka.
Research fellows: Dr. P. Stak臈nas, Dr. E. Jakubauskien臈.
Junior research fellows: I. Dalg臈dien臈, I. Pe膷iulien臈, D. Stravinskien臈, L. Vilys.
Other researchers and technical staff: D. Bakonyt臈, M. Zilnyt臈, D. Pamedytyt臈, L. Diglien臈.
Doctoral students: A. Lu膷i奴nait臈, M. Simanavi膷ius, A. Imbrasait臈.

RESEARCH INTERESTS

Monoclonal and recombinant antibodies
Molecular epidemiology of Mycobacterium tuberculosis
Alternative splicing

SELECTED PUBLICATIONS 2018

Dalg臈dien臈, I., Lu膷i奴nait臈, A., 沤virblien臈, A. 2018. Activation of macrophages by oligomeric proteins of different size and origin. Mediators of Inflammation, Article ID 7501985, 13 pages,

Simanavicius, M., Tamosiunas, P.L., Petraityte-Burneikiene, R., Johne, R., Ulrich, R.G., Zvirbliene, A., Kucinskaite-Kodze, I. 2018. Generation in yeast and antigenic characterization of hepatitis E virus capsid protein virus-like particles. Applied Microbiology and Biotechnology, vol. 102, p. 185鈥�198,

Janulaitiene, M., Gegzna, V., Baranauskiene, L., Bulavait臈, A., Simanavicius, M., Pleckaityte, M. 2018. Phenotypic characterization of Gardnerella vaginalis subgroups suggests differences in their virulence potential. PLoS One 13, e0200625,

Simanavicius, M., Juskaite, K., Verbickaite, A., Jasiulionis, M., Tamosiunas, P.L., Petraityte-Burneikiene, R., Zvirbliene, A., Ulrich, R.G., Kucinskaite-Kodze, I. 2018. Detection of rat hepatitis E virus, but not human pathogenic hepatitis E virus genotype 1-4 infections in wild rats from Lithuania. Veterinary Microbiology, vol. 221, p. 129鈥�133,

RESEARCH PROJECTS CARRIED OUT IN 2018

Projects Supported by University Budget

Development of Novel Antibodies and Testing of their Properties. Dr. A. 沤virblien臈. 2016鈥�2020.

We develop monoclonal and recombinant antibodies against different targets, mainly recombinant antigens of diagnostic relevance. Monoclonal antibodies are generated using traditional hybridoma-based technologies. For construction of recombinant antibodies, gene sequences encoding the variable parts of immunoglobulins are cloned from hybridoma cells producing antibodies against the target of interest. In 2017, large collections of monoclonal antibodies against recombinant viral antigens, including human parainfluenza virus 4 nucleocapsid protein, were generated and characterized.

National Research Projects

Research Council of Lithuania. Development of New Diagnostic Tools for Hepatitis E Virus (HEV) Infection and Studies on HEV Prevalence in Lithuania. (No. MIP-039/2015). Dr. I. Ku膷inskait臈-Kodz臈. 2015鈥�2018.

The project aims at developing novel diagnostic tests for HEV GT3 and rat HEV. In order to develop serologic assays for HEV infection, full length HEV-3 and rat HEV capsid proteins were produced in yeast, purified and examined by electron microscopy. A collection of HEV-specific monoclonal antibodies was generated. The recombinant antigens and monoclonal antibodies were used to develop IgM/IgG capture and competitive ELISAs for detection of virus-specific antibodies in blood serum. This study is performed in collaboration with Friedrich-Loeffler Institute (Germany).

Research Council of Lithuania. National program Healthy Ageing. Investigation of Genetic and Epigenetic Prognostic Markers for Prediction of Clinical Course of Papillary Thyroid Cancer (PTC) in Different age Groups. (No. SEN-14/2015). Dr. A. 沤virblien臈. 2015鈥�2018.

The project is carried out in collaboration with the Lithuanian University of Health Sciences. The aim of the project is to identify specific miRNA as biomarkers for early diagnosis of PTC and to determine their diagnostic utility for predicting disease aggressiveness and clinical outcome. The profiles of circulating miRNAs (-146b, -221, -222, -181, -21) in patients with PTC, benign nodules and healthy controls were investigated. The levels of all three miRNAs were significantly increased in PTC when compared to healthy thyroid tissue.

Research Council of Lithuania. The Prevalence and Distribution of Virulence Factors among Subgroups of Vaginal Bacteria Gardnerella Vaginalis (No. S-MIP-17-49). Dr. M. Ple膷kaityt臈. 2017鈥�2020.

Bacterial vaginosis (BV) is a microbial shift condition, characterized by the displacement of vaginal lactobacilli and the overgrowth of anaerobic bacterial populations. This projects aims to characterize the virulence features of Gardnerella vaginalis strains of different subgroups isolated from BV-negative and BV-positive women. It is also proposed to determine whether G.vaginalis secreted nucleases are related to virulence. Identification of phenotypic properties of G.vaginalis subgroups would advance our knowledge on human vaginal microbiota and promote new diagnostic and treatment options.

International Research Projects

Research Council of Lithuania. Genomic Insights into the Mechanisms of Drug Resistance, Virulence, and Transmission of Mycobacterium Tuberculosis Strains from Lithuania and Poland (No. S-LL-18-103). Dr. P. Stak臈nas. 2018鈥�2021.

With over 10 million new cases and nearly 2 million deaths every year, tuberculosis (TB) continues to be a major health problem worldwide. The key purpose of the project is to provide a comprehensive characterization of the genetic composition of Mycobacterium tuberculosis strains, representing both drug-resistant and drug-susceptible phenotypes, circulating in Lithuania and Poland. This will be accomplished through a detailed description of strain genotypes, with their comparison to each other and to those circulating in Europe and worldwide (i); assessment of TB transmission both within and between the two countries (ii); identification of the genetic polymorphisms associated with drug resistance and possibly other phenotypes (transmissibility, virulence) with evaluation of their clinical impact to diagnostic outcome in patients (iii). The project presumes a collaborative action of several TB dispensaries and laboratories operating in Poland and Lithuania, and coordinated by the University of Warsaw, in consortium with the Warsaw Medical University, and the 91桃色, on the Polish and Lithuanian side, respectively.

Contractual Research

Contract Nr. 52-1705/TPS-600000-974 with UAB Imunodiagnostika, Vilnius. Characterization of Protein Allergens and Development of Allergen-Specific Antibodies. Dr. A. 沤virblien臈. 2017鈥�2019.

The aim of this project is to investigate the antigenic and immunogenic properties of allergen extracts and allergen components used for diagnostics and immunotherapy. Both natural and recombinant protein allergens are subjected to the study. A collection of allergen-specific polyclonal and monoclonal antibodies is developed as a tool for allergen quantitation and mapping of their antigenic sites.

Contract Nr. 51-1705/TPS-600000-966 with UAB Imunodiagnostika, Vilnius. Development of Antibodies against Chemical Allergens. Dr. A. 沤virblien臈. 2017鈥�2019.

The aim of this project is to develop tools for diagnostics of drug allergy. Polyclonal and/or monoclonal antibodies against chemical compounds (haptens) that are implicated in causing drug allergy are generated. To evaluate the immunogenity of haptens, they are coupled to diferent protein carriers capable of inducing T cell-dependent B cell response in mice.

Collaboration Contract with Abcam Ltd, UK. Dr. A. 沤virblien臈 (open-ended).
Contract on the supply of monoclonal antibodies against different targets.

Collaboration Contract with Santa Cruz Biotechnology Inc., US. Dr. A. 沤virblien臈 (open-ended).
Contract on the supply of monoclonal antibodies against different targets.

Collaboration Contract with Kalon Biological/Clin-Tech Ltd, UK. Dr. A. 沤virblien臈 (open-ended).
Contract on the supply of virus-specific monoclonal antibodies.

Collaboration Contract with UAB Baltymas, Vilnius. Dr. A. 沤virblien臈 (open-ended).
Contract on the supply of virus-specific monoclonal antibodies.

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

Karolinska Institute (Sweden)
Oslo University (Norway)
Friedrich-Loeffler Institute, Institute for Novel and Emerging Infectious Diseases (Germany)
Justus-Liebig University Giessen (Germany)
ArcDia (Finland)

 

DEPARTMENT OF BIOTHERMODYNAMICS AND DRUG DESIGN

7 Saul臈tekio, LT-10257 Vilnius
Tel. 223 4364
E-mail:

Head - Dr. Daumantas Matulis

STAFF

Chief research fellows: Dr. D. Matulis, Dr. V. Smirnovas.
Senior research fellows: Dr. A Zubrien臈, Dr. V. Petrikait臈, Dr. V. Petrauskas, Dr. J. Matulien臈, Dr. V. Dudutien臈, Dr. L. Baranauskien臈, Dr. E. 膶apkauskait臈.
Research fellows: Dr. E. Kazlauskas, Dr. V. Juozapaitien臈, Dr. 艩. Grincevi膷ien臈.
Junior research fellows: V. Michailovien臈, J. Jachno, A. Zak拧auskas, Dr. J. Kazokait臈.
Other researchers and technical staff: Dr. A. Smirnov, A. Mickevi膷i奴t臈, D. Ling臈, L. Davidian, J. Tamulyt臈, V. Paketuryt臈, G. Musteikyt臈.
Doctoral students: A. Janonien臈, T. 艩neideris, J. Smirnovien臈, G. Skvarnavi膷ius, M. 沤iaunys, S. Daunys.

RESEARCH INTERESTS

We study the thermodynamics and kinetics of protein 鈥� small ligand binding and are interested in the fundamental understanding of the protein 鈥� ligand molecular recognition process. A system of 12 human carbonic anhydrases and over 900 sytnhetic sulfonamide-bearing ligands is being studied both energetically and structurally. Nearly 100 protein-ligand crystal structures were solved and deposited to the PDB. Over 5000 reactions were measured yielding the Gibbs energy, enthalpy, entropy, and volume correlations with the chemical and crystallographical structural features of the ligand and protein. Most promising compounds that bound CA IX, an anticancer target, with subnanomolar affinity and significant selectivity over other human isoforms, are being tested in cancer cell lines, and in animals for biological development as anticancer drugs.

SELECTED PUBLICATIONS 2018

Linkuvien臈, V., Zubrien臈, A., Manakova, E., Petrauskas, V., Baranauskien臈, L., Zak拧auskas, A., Smirnov, A., Gra啪ulis, S., Ladbury, J.E., Matulis, D. 2018. Thermodynamic, kinetic, and structural parameterization of human carbonic anhydrase interactions toward enhanced inhibitor design. Quarterly Reviews of Biophysics, vol. 51, p. e10, 1鈥�48,

Linkuviene, V., Talibov, V.O., Danielson, U.H., Matulis, D. 2018. Introduction of intrinsic kinetics of protein-ligand interactions and their implications for drug design. Journal of Medicinal Chemistry, vol. 61, p. 2292鈥�2302,

Zaksauskas, A., Capkauskaite, E., Jezepcikas, L., Linkuviene, V., Kisonaite, M., Smirnov, A., Manakova, E., Grazulis, S., Matulis, D. 2018. Design of two-tail compounds with rotationally fixed benzenesulfonamide ring as inhibitors of carbonic anhydrases. European Journal of Medicinal Chemistry, vol. 156, p. 61鈥�78,

Capkauskaite, E., Zubriene, A., Paketuryte, V., Timm, D.D., Tumkevicius, S., Matulis, D. 2018. Thiazole-substituted benzenesulfonamides as inhibitors of 12 human carbonic anhydrases. Bioorganic Chemistry, vol. 77, p. 534鈥�541,

Ziaunys, M., Sneideris, T., Smirnovas, V. 2018. Self-inhibition of insulin amyloid-like aggregation. Physical Chemistry Chemical Physics, vol. 20, p. 27638鈥�27645,

PATENTS 2018

Applications:
Matulis D., 膶apkauskait臈 E., Zak拧auskas A., Mork奴nait臈 V. Selective inhibitors of carbonic anhydrase. EP3328833A1. Publication date: June 06, US20180222856A1. Publication date: August 09, 2018.

RESEARCH PROJECTS CARRIED OUT IN 2018

National Research Projects

Research Council of Lithuania. Investigation of Human Carbonic Anhydrase IX as a Cancer Biomarker for Application in Cancer Diagnostics, Visualization and Prognosis (No. SEN-04/2015). Dr. J. Matulien臈. 2015鈥�2018.

Oncological diseases are one of the main causes of life quality deterioration and mortality for older people. Therefore, it is very important to develop novel, efficient and noninvasive diagnostic methods of oncological diseases (including cervical cancer) and investigate markers of cancerous processes that may be helpful in diagnosis. One of such markers could be human carbonic anhydrase IX (CA IX). There are 12 catalytically active carbonic anhydrase isoforms in the human body that catalyze the reversible reaction of carbon dioxide hydration. Most of the isoforms perform vital functions in all human tissues. However, CA IX is exceptional because it nearly does not express in healthy tissues, but highly overexpressed in hypoxic cancerous tumors. The goal of this project is to develop the methods of diagnostics and visualization of oncological diseases with the help of the technologies enabling the detection of CA IX in human tissues. To reach this goal we will use monoclonal CA IX antibodies for the immunochemical systems to determine the levels of CA IX in the patient blood and cervical cancer tissues. The potential of CA IX as a diagnostic and prognostic marker for the cervical cancer and pre-cancer stages will be evaluated. We will also analyze the potency of CA IX as a general serological marker of hypoxic tumors. Fluorescent and positron-emitting probes will be attached to CA IX antibodies and CA IX-selective inhibitors synthesized in our laboratory to analyze their potency for the visualization of cancerous tissues. This project should help solve the issues of more accurate, less invasive and earlier diagnosis of cancer and help to improve the future of older people.

Research Council of Lithuania. The Mechanism of Inhibitor Recognition by Carbonic Anhydrases - Towards Anticancer Therapy (No. S-MIP-17-87). Dr. D. Matulis. 2017鈥�2020.

Despite more than 50 years of research into biomolecular recognition, we are still not able to predict the structure of a ligand that will bind tightly to a target protein. Gaining a better understanding of the physical forces, which determine the underlying protein-ligand interactions would provide tools for the rational design of therapeutically active compounds.
There are 12 catalytically active carbonic anhydrase (CA) isoforms in human body. Their malfunction, overexpression causes numerous ailments including cancer. To tackle cancer, it is important to design inhibitors selective towards CA IX isoform and not inhibit vital isoforms, primarily CA I and CA II. However, since the active site environment in CAs is highly similar, it is a significant challenge to design isoformselective CA inhibitors. The goal of our project is to determine the factors, which are important for the selectivity towards CAs and especially CAIX. A series of novel inhibitors will be designed and synthesized by organic synthesis methods and the compound binding to human recombinant CA catalytic domains will be evaluated by biophysical techniques including fluorescent thermal shift assay, isothermal titration calorimetry, enzymatic activity stoppedflow assay, and surface plasmon resonance. The thermodynamic and kinetic parameters will be partitioned to the different structural interactions between the ligand and CA (Zn-sulfonamide bond and the contacts between the substituted benzene ring and CA). The studies with different metal substituents in the CA active site will reveal the contribution of the coordination bond and ligand substituent groups to the overall binding energetics. Thus, the project will provide deeper understanding not only of CAinhibitor interactions, but could be extended to other drug design projects where there are no highaffinity ligands available yet.

International Research Projects

Research Council of Lithuania. Design of Anticancer Pharmaceutical Compounds Using Structure and Energetics of Lead 鈥� Target Interaction (No. TAP LLT-1/2016). Dr. D. Matulis. 2016鈥�2018.

The three research teams of this proposal, Taiwanese, Latvian, and Lithuanian, have combined their efforts to improve the knowledge of protein 鈥� drug recognition and to make compounds that would be proposed to develop as drugs primarily against cancer. We have significant experience and continue to use the target-based drug discovery approach. Protein targets will be part of the epigenetic proteins, mostly metalloenzymes containing zinc in their active site. Metalloenzymes are widely distributed in human body and their mis-activity or mis-regulation causes numerous diseases.

Research Council of Lithuania. Understanding Prion Peptide Fibril-Induced Aggregation of Prion Protein (No. TAP LLT-1/2017). Dr. V. Smirnovas. 2017鈥�2019.

Prion-like spreading may be employed in a number of fatal neurodegenerative disorders, including such as Alzheimer鈥檚 and Parkinson鈥檚 diseases. Understanding all possible mechanisms of such spreading would be a big step towards curing these diseases.
Recent work showed that prion protein aggregation can be induced by short peptides. It seems that either structure of peptide-induced prion protein aggregates (piPrP) or the mechanism of its formation is different from the current knowledge in the field.
We propose a comprehensive study of piPrP structure, starting from low resolution methods as Fourier transform infrared (FTIR) spectrometry and proteinase K (PK) resistance studies, but focusing on medium and high-resolution methods in hydrogen exchange mass spectrometry (HXMS), electron spin resonance spectrometry (ESR), and solid state nuclear magnetic resonance spectroscopy (ssNMR). High resolution structure will lead to the ultimate goal of our research 鈥� getting deeper into mechanisms of prion-like self-replication of amyloid fibrils.

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

Institute of Medical Technology, University of Tampere (Finland)
University of Kaiserslautern (Germany)
Lead Generation Biology at Johnson & Johnson Pharmaceutical Research and Development (USA)
Latvian Institute of Organic Synthesis (Latvia)
Umea University (Sweden)

OTHER SCIENTIFIC ACTIVITIES

Dr. D. Matulis 鈥�

• editorial board member of the international journal BMC Biophysics;
• editorial board member of the European Biophysics Journal with Biophysics Letters;
• President-elect of the Lithuanian Biochemical Society.

 

SECTOR OF APPLIED BIOCATALYSIS

7 Saul臈tekio, LT-10257 Vilnius
Tel. 223 4371
E-mail:

Head - Dr. Inga Matijo拧yt臈

STAFF

Senior research fellow: Dr. I. Matijo拧yt臈.
Junior research fellow: R. 艩iek拧tel臈.
Other researchers: A. Veteikyt臈, affiliated prof. G. Dienys.

RESEARCH INTERESTS

Biocatalysts and their application

SELECTED PUBLICATIONS 2018

Malunavicius, V., Druteika, G., Sadauskas, M., Veteikyte, A., Matijosyte, I., Lastauskiene, E., Gegeckas, A., Gudiukaite, R. 2018. Usage of GD-95 and GD-66 lipases as fusion partners leading to improved chimeric enzyme LipGD95-GD66. International Journal of Biological Macromolecules, vol. 118, p. 1594鈥�1603,

Sulciene, M., Kolvenbach, B., Ammann, E., Matijosyte, I. 2018. Towards an affordable enzymatic production of biopolyols - Comparing the immobilization of lipases by two optimized techniques. International Journal of Biological Macromolecules, vol. 116, p. 1049鈥�1055,

RESEARCH PROJECTS CARRIED OUT IN 2018

Projects Supported By University Budget

Development and Application of Biocatalysts and Biocatalytic Systems. Dr. I. Matijo拧yt臈. 2018鈥�2020.

The research was directed towards development of biocatalysts with novel activities by three common ways: screening of enzymes, development of biocatalyst and application of biocatalyst. In 2018 the research was focused on development of screening systems for targeted enzyme activities, development of protein expression systems for production of targeted enzymes and exploring carrier-free immobilization methods.

Contractual Research

Investigation of the Biomaterial Treatment by Chemical and Biotechnological Methods. JSC Nagenus, N掳 MTS-600000-2032, Lithuania, Dr. I. Matijo拧yt臈.

The aim is to evaluate and define the best treatment method and opimal conditions of three different kidn of biomass.

Investigation of Biogeocenosis Features of Microorganism. JSC Bioenergy LT, N掳 MTS-600000-139, Lithuania, Dr. I. Matijo拧yt臈.

The aim of project was to investigate the company's biological products, microorganisms, for their biogeocenosis properties.

Optimization of Casein Hydrolysis. Pienas LT, N掳 MTS-15600-1340, Lithuania, Dr. I. Matijo拧yt臈.

The aim was to optimize the process of enzymatic casein hydrolysis.

Collaboration Contracts

Cooperation on biotransformations of various lignocellulosic based biomass into added-value products. Latvian State Institute of Wood Chemistry, Cooperation Agreement N掳 BS-15600-1341 (July 30, 2018, I. Matijo拧yt臈 (open-ended).
Enzymes and their application in detergents. SC Naujoji Ringuva, N掳 B1-560000-153, I. Matijo拧yt臈 (open-ended).

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

Latvian State Institute of Wood Chemistry (Latvia)
University of Applied Sciences Northwestern (Switzerland)
University of Ljubljana (Slovenia)
National Institute of Biology (Slovenia)
Leiden University (the Netherlands)
University of Milan (Italy)

OTHER SCIENTIFIC ACTIVITIES

Dr. I. Matijo拧yt臈 -

• national representative in State Representative Group (SRG) at Bio-Based Industry Joint Undertaking;
• president of Lithuanian Biotechnology Association;
• scientific member of European Section of Applied Biocatalysis (ESAB, EFB).

 

DEPARTMENT OF BIOINFORMATICS

7 Saul臈tekio, LT-10257 Vilnius
Tel. 223 4368
E-mail:
Website:

Head - Dr. 膶eslovas Venclovas

STAFF

Chief research fellow: Dr. 膶. Venclovas.
Senior research fellows: Dr. V. Kairys, Dr. M. Margelevi膷ius.
Research fellows: Dr. J. Dapk奴nas, Dr. A. Timinskas, Dr. D. Kazlauskas, Dr. K. Olechnovi膷.
Other researcher: K. Timinskas.
System administrator: R. Di膷i奴nas.
Doctoral student: A. Naus臈das.

RESEARCH INTERESTS

Protein three-dimensional (3D) structure modeling
Analysis of 3D structure of proteins and nucleic acids
Analysis of genomes and proteomes
Distant homology detection between protein families
Protein-protein and protein-nucleic acids interactions
Molecular mechanisms of DNA replication, recombination and repair in the context of 3D structures

SELECTED PUBLICATIONS 2018

Toliusis, P., Tamulaitiene, G., Grigaitis, R., Tuminauskaite, D., Silanskas, A., Manakova, E., Venclovas, C., Szczelkun, M.D., Siksnys, V., Zaremba, M. 2018. The H-subunit of the restriction endonuclease CglI contains a prototype DEAD-Z1 helicase-like motor. Nucleic Acids Research, vol. 46, p. 2560鈥�2572,

Drabavicius, G., Sinkunas, T., Silanskas, A., Gasiunas, G., Venclovas, 膶., Siksnys, V. 2018. DnaQ exonuclease-like domain of Cas2 promotes spacer integration in a type I-E CRISPR-Cas system. EMBO Reports, vol. 19, e45543,

Wolf, Y.I., Kazlauskas, D., Iranzo, J., Luc铆a-Sanz, A., Kuhn, J.H., Krupovic, M., Dolja, V.V., Koonin, E.V. 2018. Origins and Evolution of the Global RNA Virome. mBio 9, e02329鈥�18,

Margelevicius, M. 2018. A low-complexity add-on score for protein remote homology search with COMER. Bioinformatics, vol. 34, p. 2037鈥�2045,

Kazlauskas, D., Sezonov, G., Charpin, N., Venclovas, C., Forterre, P., Krupovic, M. 2018. Novel families of archaeo-eukaryotic primases associated with mobile genetic elements of bacteria and archaea. Journal of Molecular Biology, vol. 430, p. 737鈥�750,

RESEARCH PROJECTS CARRIED OUT IN 2018

Projects Supported by University Budget

Computational Studies of Protein Structure, Function and Evolution. Dr. 膶. Venclovas. 2017鈥�2019.

Our main focus in methods development continued to be the estimation of protein structure accuracy and the analysis of protein-protein interactions. Along with methods development, our major efforts were directed at application of computational methods to studies of prokaryotic CRISPR-Cas defence systems (jointly with Prof. Virgis Siksnys) and archaeo-eukaryotic primases in bacterial genomes (jointly with Dr. Mart Krupovic at Institut Pasteur, Paris).

National Research Projects

Research Council of Lithuania/European Social Fund. Computational Study of Evolutionary Relationships, Genomic Distribution, Structural and Functional Properties of DNA Polymerases (No. 09.3.3-LMT-K-712-01-0080). Dr. 膶. Venclovas. 2018鈥�2022.

The goal of this project is to significantly advance the knowledge regarding DNA polymerases at the same time improving scientific qualification of the members of research team. This goal will be achieved by carrying out research activities directed at enriching the scientific knowledge related to structures, interactions, functional properties and evolutionary relationships of DNA polymerases. The proposed research will encompass all three domains of life 鈥� eukaryotes, bacteria and archaea. We will perform the proposed research by analyzing and integrating different types of publicly available biological data using cutting-edge methods of computational biology and bioinformatics. We will classify all of the identified DNA polymerases and will characterize in detail their structural and functional properties. We will also pursue the characterization of structural-functional assemblies involving DNA polymerases and the associations between DNA polymerases and recently discovered prokaryotic CRISPR-Cas immune systems. Furthermore, we will identify sets of DNA polymerases and their functional modules encoded in genomes of individual organisms. We will then try to understand whether and if so, how the nature of the polymerase set possessed by a given organism is linked to the global characteristics of both the organism and its living environment.

Research Council of Lithuania/European Social Fund. A System of Restful Web Services for Protein Remote Homology Search in Real Time and Protein Modeling (No. 01.2.2-LMT-K-718-01-0028). Dr. M. Margelevi膷ius. 2018鈥�2022.

Protein structure prediction from amino acid sequence is one of the most important problems in bioinformatics, the successful addressing of which would impact the entire field of biomedicine. The most reliable approach for predicting protein structure today is modeling by homology established by alignment of sequence families. The goal of the project is to increase the sensitivity of homology detection and alignment accuracy and develop convenient and fast computational tools allowing researchers to search for protein homologues in real time, perform evolutionary analysis, and predict protein structures. Achieving this goal includes the development of a general methodology for estimating the statistical significance of alignments between sequence families, a critical issue in homology search. Software implementing the methodology and a search engine developed using high-performance computing technologies will provide a means for extremely fast sensitive homology search, which will underlie protein evolutionary studies and structure modeling by alignment of sequence families on a new web service platform. New developments are expected to be useful for both evolutionary analysis of selected proteins and analysis performed on a large scale in a real-time environment, contributing to a deeper understanding of biological processes.

Research Council of Lithuania. Analysis and Prediction of Structural Features of Proteins and Protein Complexes Using Interatomic Contact Areas and Evolutionary Information (No. S-MIP-17-60). Dr. 膶. Venclovas. 2017鈥�2020.

The knowledge of three-dimensional structure of proteins and protein complexes is critical for comprehensive understanding of their molecular function. However, experimental determination of protein structure is often tedious or unsuccessful. Currently, a feasible alternative to experiments is computational prediction of protein structure. Computational methods are also indispensable for the analysis of protein structure regardless of whether it is solved experimentally or derived using computational modeling. However, at present it is often difficult to estimate how accurate the computationally derived protein structural model is. The same is true for structural models of protein complexes. Better computational methods for the analysis and prediction of protein binding sites are also in high demand. In this project, we are going to develop computational methods to estimate the accuracy of protein models, to assess the accuracy of protein-protein interfaces, to predict unknown binding sites in proteins and to improve analysis of protein-nucleic acids complexes.

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

Most Departments at 91桃色 Institute of Biotechnology (Lithuania)
Institute of Molecular and Cell Biology, University of Tartu (Estonia)
Institut Pasteur, D茅partement de Microbiologie, Paris (France)
University of Cape Town (South Africa)

OTHER SCIENTIFIC ACTIVITIES

Dr. 膶. Venclovas 鈥�

• editorial board member of Scientific Reports (Nature Publishing Group);
• member of the Lithuanian Academy of Sciences.

 

LABORATORY OF MEDICAL EPIGENOMICS

7 Saul臈tekio, LT-10257 Vilnius
E-mail:

Head - Dr. Art奴ras Petronis

STAFF

Chief research fellow: Dr. A. Petronis.
Junior research fellows: A. Kri拧膷i奴nas, K. Koncevi膷ius.
Other researcher: T. Bareikis.

SELECTED PUBLICATIONS 2018

Oh, G., Ebrahimi, S., Carlucci, M., Zhang, A., Nair, A., Groot, D.E., Labrie, V., Jia, P., Oh, E.S., Jeremian, R.H., Susic, M., Shrestha, T.C., Ralph, M.R., Gordevi膷ius, J., Koncevi膷ius, K., Petronis, A. 2018. Cytosine modifications exhibit circadian oscillations that are involved in epigenetic diversity and aging. Nature Communications, vol. 9, p. 644,

Gordevicius, J., Krisciunas, A., Groot, D.E., Yip, S.M., Susic, M., Kwan, A., Kustra, R., Joshua, A.M., Chi, K.N., Petronis, A., Oh, G. 2018. Cell-free DNA modification dynamics in abiraterone acetate-treated prostate cancer patients. Clinical Cancer Research, vol. 24, p. 3317鈥�3324,

Wang, D., Kosowan, J., Samsom, J., Leung, L., Zhang, K., Li, Y., Xiong, Y., Jin, J., Petronis, A., Oh, G., Wong, A.H.C. 2018. Inhibition of the G9a/GLP histone methyltransferase complex modulates anxiety-related behavior in mice. Acta Pharmacologica Sinica, vol. 39, p. 866鈥�874,

 

INSTITUTE OF BIOCHEMISTRY

7 Saul臈tekio, LT-10257
Tel. 223 4378
E-mail:

Director - Dr. Kastis Krik拧topaitis

DEPARTMENTS OF THE INSTITUTE

Department of Bioanalysis
Department of Bioelectrochemistry and Biospectroscopy
Department of Biological Models
Department of Molecular Cell Biology
Department of Molecular Microbiology and Biotechnology
Department of Xenobiotics Biochemistry
Laboratory of Bioorganic Compounds Chemistry
Proteomics Centre

RESEARCH AREAS

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

DOCTORAL DISSERTATIONS MAINTAINED IN 2018

S. Baronait臈. The studies of amniotic fluid and amniotic fluid stem cells.
A. Au膷ynait臈. Metabolic enzymes of modified nucleotides.
R. Jara拧ien臈-Burinskaja. Investigation of quinone and polyphenol xenobiotic induced molecular mechanisms of death in mouse hepatoma cells.
G. Valiulien臈. Epigenetic regulation and leukemia 鈥� research of novel biologic, molecular and therapeutic aspects.

MAIN CONFERENCES ORGANIZED IN 2018

21st international conference Laboratory animals in research

 

DEPARTMENT OF BIOANALYSIS

7 Saul臈tekio, LT-10257
Tel. 223 4389
E-mail:

Head 鈥� Dr. Marius Dagys

STAFF

Senior research fellows: Dr. J. Razumien臈, Dr. R. 艩imkus, Dr. R. Vid啪i奴nait臈.
Research fellows: Dr. L. Tetianec, Dr. M. Dagys, Dr. I. 艩akinyt臈.
Junior research fellows: I. Bratkovskaja, A. Lauryn臈nas.
Senior specialist: V. Gurevi膷iene.
Doctoral students: J. Gru啪auskait臈, D. Ratautas, I. Jurkevi膷i奴t臈, M. Butkevi膷ius, E. Ramonas.

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 2018

Project Supported by University Budget

Design and Investigation of New Systems for Biocatalysis. Dr. J. Razumien臈. 2017鈥�2020.

Investigation of the action of laccase containing systems on nano-structured surfaces. Different oxidoreductases were applied for the creation of mediatorless bio-anodes and bio-cathodes in bio-solar cells, bio-batteries and bio-fuel cells.
The development of artificial nanocatalysts, especially those incorporating the highly active biocatalysts (enzymes) present in nature, is a rapidly developing field in nanocatalysis and nanomaterials science. Dehydrogenases are exceptionally attractive, as they catalyze the oxidation of various cheap/common substrates to more expensive and desired products. We designed a unique nanomaterial composed of two redox enzymes (nonspecific glucose dehydrogenase and oxygen-reducing laccase) and gold nanoparticles. Both enzymes had been wired through the gold nanoparticles (10 nm) and direct electrochemical 鈥渃ommunication鈥� was achieved, allowing electron transfer from the redox center of glucose dehydrogenase to a copper center of laccase. As a result, self-sufficient nanocatalysts were synthesized and shown to oxidize various carbohydrates directly with molecular oxygen.

Novel 1,5-benzodiazepine oxime derivatives were characterized by physicochemical methods prior to the studies of their enzymatic reactions.

Main publications:

Ratautas, D., Ramonas, E., Marcinkevi膷ien臈, L., Me拧kys, R., Kulys, J. 2018. Wiring gold nanoparticles and redox enzymes: a self-sufficient nanocatalyst for oxidation of carbohydrates directly with the molecular oxygen. Chem. Cat. Chem., vol. 10, p. 1鈥�5,  doi:

Rekovi膷, L., Kosychova, L., Bratkovskaja, I., 沤ukauskait臈, V., Vid啪i奴nait臈, R. 2018. Electrochemical characterization of 1,5-benzodiazepine oximes in organic solvents. Chemija, vol. 29, p. 235鈥�242.

National Research Projects

Agency for Science, Innovation and Technology. Development of Carbamide Analyser for Measurements in Industrial Media (No. TPP-01-054, LSS-600000-327). Dr. J. Razumien臈. Partner 鈥� UAB 鈥淏ioanaliz臈s sistemos鈥�. 2017鈥�2018.

The project resulted in creation of automatic and portable analyser (production trial batch) for urea measurements in fertilizer samples.

Research Council of Lithuania. Development of Non-Invasive Method Platform for Early Diagnostics and Prognosis of Acute Pancreatitis (No. 01.2.2-LMT-K-718-01-0025). Dr. J. Razumien臈. Partner 鈥� 91桃色 Hospital Santaros Klinikos. 2018鈥�2022.

This recently started project aims at developing a clinically significant, non-invasive biosensor platform based method, capable of predicting the severity of pancreatitis for the patient based on eraly sample analysis.

Research Council of Lithuania. Biocatalytic Systems for Conversion of non-starch poli- and Oligosaccharides (No. 01.2.2-LMT-K-718-01-0019). Dr. M. Dagys. 2018鈥�2022.

Another recently started project, whose goal is to develop a high-yield biocatalytic scalable system for oxidation of otherwise wasted non-starch poly- and oligosaccharides, which would result in production of high value product 鈥� aldonic acids.

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

Vilnius Gediminas Technical University (Lithuania)
Malmo University (Sweden)
Lund University (Sweden)
Institute of Molecular Biology and Genetics of the National Academy of Science of Ukraine (Ukraine)
UAB Bioanaliz臈s sistemos (Lithuania)
UAB Ubique calculus (Lithuania)
UAB Sentiero Baltic (Lithuania)


DEPARTMENT OF BIOELECTROCHEMISTRY AND BIOSPECTROSCOPY

7 Saul臈tekio, LT-10257 Vilnius
Tel. 223 4394
E-mail:

Head 鈥� Dr. Gintaras Valin膷ius

STAFF

Chief research fellows: Dr. G. Valin膷ius and Habil.Dr. G. Niaura (part-time).
Senior research fellow: Dr. G. Preta.
Research fellows: Dr. R. Budvytyt臈, Dr. M. Jankunec, Dr. T. Ragaliauskas.
Junior research fellow: Dr. B. Pavliukevi膷ien臈.
Senior specialists: M. Talaikis, Dr. A. Bulovas.
Doctoral students: I. Aleknavi膷ien臈, T. Penkauskas, J. Borzova, K. Majauskaite, F. Ambrulevi膷ius.

RESEARCH FIELDS

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 2018

Project Supported by University Budget

Spectroelectrochemical Studies of Biological Systems and Their Models. Dr. G. Valin膷ius. 2016鈥�2018.

The formation of functional tethered bilayer membranes (tBLM) were accomplished on a number of metal oxide surfaces providing a novel experimental platform for membrane protein interaction studies. Specifically, the commercially available fluorine doped tin oxide (FTO) films on glass were functionalized by the octadecyltrichlorosilane (OTS) self-assembled monolayers (SAM), which upon exposure to a multilamellar phospholipid vesicle solutions trigger vesicle fusion and formation of a tBLM. The formation of the tBLM can be monitored in real-time by the Fast Fourier Transform (FFT) electrochemical impedance spectroscopy (EIS), which attested the completion of the fusion process within 2000 s. Highly insulating phospholipid bilayers were accomplished using silane anchor chemistry also on a titanium metallurgic sheet. This provides evidence of possibility to functionalize titanium monoliths used in medical implant technologies. The phospholipid bilayers then can be loaded with protein (peptide) or other biologically active compounds, which can provide specific biological function to the surface of an implant. In collaboration with the Faculty of Mathematics and Informatics at 91桃色 we continued developing mathematical analysis tools for the electrochemical impedance response from tBLMs. Specifically, impact of heterogeneity on EIS response was analysed. The results were presented at the coference of International Society of Electrochemistry. The manuscript describing analytical and numerical solutions of the EIS response was submitted to the the specialized international research journal. The developed analysis should lead to practical methodologies using tBLMs in biosensor technologies and applications.

Main publications:

Sabirovas, T., Vali奴nien臈, A., Valin膷ius, G. 2018. Mechanically polished titanium surface for immobilization of hybrid bilayer membrane. J. Electrochem. Soc., vol. 165(10), p. G109鈥揋115.
Gabri奴nait臈, I., Vali奴nien臈, A., Valin膷ius, G. 2018. Formation and properties of phospholipid bilayers on fluorine doped tin oxide electrodes. Electrochimica Acta, vol. 283, p. 1351鈥�1357.
Penkauskas, T., Preta, G. 2018. Biological applications of tethered bilayer lipid membranes. Biochimie, vol. 157, p. 131鈥�141.
Santos, A. L., Preta, G. 2018. Lipids in the cell: organization regulates function. Cell Mol Life Sci., vol. 75(11), p. 1909鈥�1927.
Kausteklis, J., Talaikis, M., Aleksa, V., Balevi膷ius, V. 2018. Raman spectroscopy study of water confinement in ionic liquid 1-butyl-3-methylimidzolium nitrate. J. Mol. Liq., vol. 271, p. 747鈥�755.

Contractual Research

Biosensors for Bacterial Toxin Detection (BIOSENTOX), UAB Energenas, funded by Lithuanian Business Support Agency (LPVA).

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

Faculty of Mathematics and Informatics, 91桃色 (Lithuania)
Institute of Neurosciences, Lithuanian University of Health Sciences (Lithuania)
Institute of Chemistry, Center for Physical Sciences and Technology (Lithuania)
Institute for Biosciences and Biotechnology Research, University of Maryland, Rockville, MD (USA)
NIST Center for Neutron Research, Gaithersburg, MD (USA)
Department of Biomedical Sciences, Faculty of Health and Society, Malm枚 University, Malm枚 (Sweden)
Institute of Lifescience, Swansea University (United Kingdom)

OTHER SCIENTIFIC ACTIVITIES

Dr. G. Valin膷ius 鈥�

• editorial board member of the journal Chemija;
• member of the Lithuanina Biophysical Society;
• member of the Lithuanian Biochemical Society;
• member of International Society of Electrochemistry;
• expert of Research and Higher Education Monitoring and Analysis Centre (MOSTA).

Habil. Dr. G. Niaura 鈥�

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

Dr. R. Budvytyt臈 鈥�

• member of the American Biophysical Society.

 

DEPARTMENT OF BIOLOGICAL MODELS

7 Saul臈tekio, LT-10257 Vilnius
Tel. 223 4408
E-mail:

Head 鈥� Dr. Virginija Bukelskiene

STAFF

Senior research fellows: Dr. V. Bukelskien臈, Dr. D. Baltriukien臈.
Junior research fellows: Dr. R. Jara拧ien臈-Burinskaja, E. Bal膷i奴nas.
Specialist: A. 艩膷erbavi膷ien臈.
Doctoral students: M. Alksn臈, E. M. Me拧kyt臈, I. Rink奴nait臈, E. 艩imoli奴nas.

RESEARCH INTERESTS

Laboratory animals, cell culture, stem cells, tissues engineering

RESEARCH PROJECTS CARRIED OUT IN 2018

Projects Supported by University Budget

Development of the Cell Technologies for Regenerative Medicine and Their Evaluation on Biological Models. Dr. V. Bukelskien臈. 2014鈥�2018.

Study of cell interactions with scaffolds of different chemical composition. Two materials - hydroxyapatite (HA) and bioglass (BG) - were chosen for the preparation of composite polylactic acid (PLA) scaffolds. In addition, biological modification of the scaffolds has been done using the cell-derived extracellular matrix. The results of the studies showed that cells grown on these different composite and biologically modified surfaces behaved differently. The most effective modification appeared biological coating of the PLA surface. It noticeably increased cell proliferation and adhesion. Also, it promoted the formation of the intracellular matrix characteristic for bone tissue. However, molecular study showed that the expression of osteogenic differentiation genes was enhanced by composite prepared from PLA and BG.
This knowledge opens the door to finding new, even better combinations, for creating the right artifficial bone structure designed for the substitution of bone tissue.

National Research Projects

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. Rutk奴nas (VU Faculty of Medicine, Institute of Odontology). 2015鈥�2018.

Production of precise micro- and nano- structured scaffolds for tissue engineering, which is known to enhance osteogenic differentiation, is expensive and time-consuming. The research was focused on polylactic acid scaffold's macro-pattern impact on rat鈥檚 dental pulp stem cells (DPSC) morphology, proliferation and osteogenic differentiation. For this study, two types of scaffolds were 3D printed: wavy and porous. Wavy scaffolds consisted of 188 渭m wide joined threads, meaning that cells might have been curved on the filament as well as compressed in the groove. Porous scaffolds were designed to avoid groove formation and consisted of 500 渭m threads, arranged in the woodpile manner, forming 300 渭m diameter pores. We found that both macro-surfaces influenced DPSC morphology compared to control. As a consequence, enhanced DPSC proliferation and increased osteogenic differentiation potential was registered in cells grown on these scaffolds. Our results showed that the construction of an artificial bone did not necessarily require the precise structuring of the scaffold, because both types of macro-topographic PLA scaffolds were sufficient enough to induce spontaneous DPSC osteogenic differentiation. Efficiency of such scaffolds structure vere proved in the studies in vivo.

Main publication:

Alksn臈, M., 艩imoli奴nas, E., Kalvaityte, M., Skliutas, E., Rinkunaite, I., Gendviliene, I., Baltriukiene, D., Rutkunas, V., Bukelskiene, V. 2019. The effect of larger than cell diameter polylactic acid surface patterns on osteogenic differentiation of rat dental pulp stem cells. Journal of Biomedical Materials Research: Part A., vol. 107A, p. 174鈥�186.

Research Council of Lithuania. Science Programme Healthy Aging project Soft Tissue Engineering: From Cell to Artificial Tissue (No. SEN-13/2015). Dr. D. Baltriukien臈. 2015鈥�2018.

Novel biocompatible films based on UV curable hydrophilic copolymers containing siloxane units were prepared. These films exhibited good wettability due to hydrophilic units of copolymer, good biocompatibility in vitro and in vivo, and elasticity due to the introduction of the siloxane units as grafts to the backbone of hydrophilic copolymer and the good mechanical properties mainly due to crosslinked structure of films. The optimal parameters required for the microstructurization of the scaffolds were also determined. The optimized processing methodology for scaffold preparation was developed.

Main publication:

Kilikevi膷ius, A., Bal膷i奴nas, E., Kilikevi膷iene, K., Maknickas, A., Bukelskien臈, V., Baltriukien臈, D., Kacianauskas, R. 2018. Modelling of silk-reinforced PDMS properties for soft tissue engineering applications. Technology and Health Care, vol. 26 (2), p. S679鈥揝688.

International Research Projects

COST Action CA16119 In vitro 3-D total cell guidance and fitness (CellFit). Dr. D. Baltriukien臈. 2017鈥�2021.

Contractual Research

To assess feed additives toxicity by using laboratory mice; Centrinis parkas, UAB; Dr. V. Bukelskien臈.
Evaluation of products biological activity, Valentis, UAB. Dr. V. Bukelskien臈.
Study of the biocompatibility and differentiation potential of anisotropic composite and anisotropic bioactive composite scaffolds in vitro (using human / animal primary cell cultures) and in vivo (using laboratory rabbits); 3D Creative, UAB. Dr. V. Bukelskien臈.
In vitro and in vivo study of the biocompatibility of new materials; Prodentum, UAB. Dr. V. Bukelskien臈.

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

91桃色, Faculty of Physics, Laser Research Centre
91桃色, Faculty of Chemistry
91桃色, Faculty of Medicine
91桃色, Hospital Santaros klinikos, Centre of Heart Surgery
91桃色, Faculty of Medicine, Institute of Odontology
Vilnius Gediminas Technical University, Faculty of Fundamental Sciences, Department of Chemistry and Bioengineering
UAB Thermo Fisher Scientific Baltics
UAB Prodentum
UAB Centrinis parkas
UAB Experimentica
Department of Chemistry and Materials Science Institute, Lancaster University (UK)
Laboratory of Molecular Cancer Genetics CiBiO, University of Trento (Italy)
Department of Neuroscience, Uppsala University (Sweden)

OTHER SCIENTIFIC ACTIVITIES

Dr. D. Baltriukien臈 鈥�

• president of Baltic Laboratory Animal Science Association,
• board member of the FELASA (Federation of European Laboratory Animal Science Associations),
• board member of the Lithuanian Stem Cell Researchers Association,
• member of the Lithuanian Biochemical Society.

Dr. V. Bukelskien臈 鈥�

• board member of Baltic Laboratory Animal Sciensce Association, ();
• board member of FELASA (Federation of European Laboratory Animal Science, Associations, );
• scientific supervisor of the Extramural School of Young Biochemists at Lithuanian Centre of Non-formal Youth Education,
• member of the Lithuanian Biochemical Society.

DEPARTMENT OF MOLECULAR CELL BIOLOGY

7 Saul臈tekio, LT-10257 Vilnius
Tel. 223 4409
E-mail:

Head 鈥� Prof. Dr. R奴ta Navakauskien臈

STAFF

Chief research associate: Prof. Dr. R. Navakauskien臈.
Senior research fellows: Dr. V. V. Borutinskait臈, Dr. A. Kalvelyt臈.
Research fellows: Dr. A. Imbrasait臈, Dr. G. Treigyt臈, Dr. G. Valiulien臈.
Junior research fellow: Dr. N. Krestnikova.
Doctoral students: R. Bau拧yt臈, M. Gasi奴nien臈, A. Stulpinas, A. Vaitkevi膷ien臈, A. Zentelyt臈.

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 2018

Project Supported by University Budget

Studies of Regulatory Mechanisms of Cancer and Stem Cell for New Technologies of Personalized Medicine. Prof. R. Navakauskien臈. 2014鈥�2018.

Assessement of changes in epigenetic landscape in stem and cancer cells during ageing. Human cancer cells (acute myeloid leukemia and lung cancer) as well as stem cells isolated from human perinatal derivatives are used to study cell functioning and regulation.
It is known for decades that mitogen-activated protein kinases (MAPKs) regulate cell functions, such as proliferation, differentiation and programmed cell death. MAPKs mediates cellular response to anticancer drugs and are candidates in improving effectiveness of targeted and conventional chemotherapies. In present study, the dynamic changes in phosphorylation of MAP kinases JNK, ERK and p38 were investigated during cisplatin, well known inducer of apoptosis, treatment by using various cancer cell models in vitro.
The role of connexin 43, the most abundant heart gap junctional protein, in apoptosis regulation has been analysed in muscle-derived stem cells induced differentiate along myogenic lineage. The results of our study proved the proapoptotic role of Cx43 in differentiated Myo cells.

Main publications:

Vitkevi膷ien臈, A., Bak拧ien臈, S., Borutinskait臈, V., Navakauskien臈, R. 2018. EGCG and BIX-01294 have different impact on epigenetics and senescence modulation in acute and chronic myeloid leukemia cells. European Journal of Pharmacology, vol. 838, p. 32鈥�40.

Borutinskait臈, V, Virk拧ait臈, A, Gudelyt臈, G, Navakauskien臈, R. 2018. Green tea polyphenol EGCG causes anti-cancerous epigenetic modulations in acute promyelocytic leukemia cells. Leukemia Lymphoma, vol. 59(2), p. 469鈥�478.

Gasi奴nien臈, M., Zubova, A., Utkus, A., Navakauskien臈, R. 2018. Epigenetic and metabolic alterations in human amniotic fluid stem cells induced to cardiomyogenic differentiation by DNA methyltransferases and p53 inhibitors. J Cell Biochem., doi: 10.1002/jcb.28092.22.

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. Navakauskien臈. 2015鈥�2018.

Conventional treatment of acute promyelocytic leukemia (APL) with retinoic acid and chemotherapeutics is quite satisfactory. However, there are still patients who develop resistance to treatment with retinoic acid. Thus, we studied the potential of histone deacetylase (HDAC) inhibitor and histone methyl transferase (HMT) inhibitor to enhance conventional therapy in vitro and ex vivo. In vitro and ex vivo models showed similar response to the treatment with different combinations of 3-Deazaneplanocin A, Belinostat, retinoic acid and Idarubicin. Furthermore, 3-Deazaneplanocin A and Belinostat enhanced conventional APL treatment.

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

Amniotic fluid derived mesenchymal stem cells (AF-MSC) are autologous to the fetus and represent a potential alternative source for regenerative medicine and the treatment of prenatal disorders. To date, AF-MSCs differentiation capacity to non-mesodermal lineages and epigenetic regulation are still poorly characterized. We investigated differentiating potential toward the neural-like cells in comparison with the mesodermal myogenic differentiation of AF-MSCs of normal and fetus-affected gestations and epigenetic factors involved in tissues-specific differentiation. We report that both AF-MSCs of normal and fetus-affected gestations possess differentiation capacity toward myogenic and neural lineages through rather similar epigenetic mechanism that may provide potential uses for investigation of molecular basis of prenatal diseases and for future autologous therapy.

Research Council of Lithuania. Designing of the Patient-Specific, Heterogeneous Lung Cell Ex Vivo Model System for Drug Efficiency Prediction in Personalized Oncotherapy (No 01.2.2-LMT-K-718-01-0072). Dr. A. Kalvelyt臈. 2018鈥�2022.

The effectiveness of conventional and targeted drugs, selected to target the intracellular signal transducing protein kinases, was studied by using patient-derived sets of heterogeneous lung cancer cell lines as a model system. Phenotype switching, cell dynamic state, extracellular contacts, along with the identification of molecular mechanisms, were assessed during the evaluation of drug effectiveness.

International Research Projects

COST action BM1402: Development of a European Network for Preclinical Testing of Interventions in Mouse Models of Age and Age-Related Diseases (Mouseage). Prof. R. Navakauskien臈. 2014鈥�2018.
COST action CA15138: European Network of Multidisciplinary Research and Translation of Autophagy Knowledge (TRANSAUTOPHAGY). Dr. V. Borutinskait臈. 2015鈥�2019.
COST Action CA17116: International Network for Translating Research on Perinatal Derivatives into into Therapeutic Approaches (SPRINT). Prof. R. Navakauskien臈. 2018鈥�2022.

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. Navakauskien臈 鈥�

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

Dr. A. V. Kalvelyt臈 鈥�

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

Dr. V. Borutinskait臈 鈥�

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

Dr. A. Imbrasait臈 鈥�

• member of Federation of European Biochemical Society.

Dr. N. Krestnikova 鈥�

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

PhD students M. Gasi奴nien臈, A. Stulpinas, A. Virk拧ait臈, A. Zentelyt臈 鈥�

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

DEPARTMENT OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY

7 Saul臈tekio, LT-10257 Vilnius
Tel. 223 4386
E-mail:

Head 鈥� Dr. Rolandas Me拧kys

STAFF

Chief research fellow: Dr. R. Me拧kys.
Senior research fellows: Dr. V. 膶asait臈, Dr. D. Taurait臈, Dr. L. Truncait臈, Dr. J. Urbonavi膷ius (part-time).
Research fellows: Dr. R. Gasparavi膷i奴t臈, Dr. L. Kalinien臈, Dr. R. Rutkien臈, Dr. S. Povilonien臈, Dr. J. Stankevi膷i奴t臈, Dr. A. Zajan膷kauskait臈, Dr. E. 艩imoli奴nas.
Junior research fellows: R. Me拧kien臈, Dr. R. Stanislauskien臈, J. Vaitek奴nas, Dr. A. Au膷ynait臈, V. Petkevi膷ius.
Doctoral students: J. Jakubovska, M. Sadauskas, N. Urbelien臈, A. Krik拧taponis, A. Noreika, M. 艩imoli奴nien臈.

RESEARCH INTERESTS

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

RESEARCH PROJECTS CARRIED OUT IN 2018

Project Supported by University Budget

Investigation of Genetic and Biochemical Diversity of Bacteriophages and Microorganisms. Dr. R. Me拧kys. 2014鈥�2018.

Bacterial degradation of pyrazines and hydroxypyridines has been demonstrated for a number of cases; however, very little is known about genes and proteins involved in this process. A functional characterization of genes responsible for 2-hydroxypyridine biodegradation in Burkholderia sp. MAK1 has been carried out. Catabolic cascade was reconstituted in vivo with recombinant proteins and each protein was assigned an enzymatic function. This work provides the first insights into genetic background of microbial 2-hydroxypyridine biodegradation via a maleamate pathway.

Main publications:

Petkevi膷ius, V., Vaitek奴nas, J., Stankevi膷i奴t臈, J., Gasparavi膷i奴t臈, R., Me拧kys, R. 2018. Catabolism of 2-hydroxypyridine by Burkholderia sp. MAK1: a five-gene cluster encoded 2-hydroxypyridine 5-monooxygenase HpdABCDE catalyses the first step of biodegradation. Appl. Environ. Microbiol., vol. 84(11), p. e00387鈥�18, doi: 10.1128/AEM.00387-18.

Stanislauskien臈, R., Kutanovas, S., Kalinien臈, L., Bratchikov, M., Me拧kys, R. 2018. Tetramethylpyrazine-inducible promoter region from Rhodococcus jostii TMP1. Molecules, vol. 23(7), p. 1530, doi: 10.3390/molecules23071530.

National Research Projects

Research Council of Lithuania. Novel Prodrug Activation Systems for Cancer Genotherapy (No. SEN-07/2015). Dr. J. Urbonavi膷ius. 2015鈥�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.

Main publications:

Au膷ynait臈, A., Rutkien臈, R., Gasparavi膷i奴t臈, R., Me拧kys, R., Urbonavi膷ius, J. 2018. A gene encoding a DUF523 domain protein is involved in the conversion of 2-thiouracil into uracil. Environ. Microbiol. Rep., vol. 10(1), p. 49鈥�56, doi: 10.1111/1758-2229.12605.

Au膷ynait臈, A., Rutkien臈, R., Taurait臈, D., Me拧kys, R., Urbonavi膷ius, J. 2018. Discovery of bacterial deaminases that convert 5-fluoroisocytosine into 5-fluorouracil. Front. Microbiol., vol. 9, p. 2375, doi: 10.3389/fmicb.2018.02375.

Research Council of Lithuania. Agroecosystems Microbiota under Climate Change: Structure and Concordance Mechanisms (No. SIT-7/2015). Dr. E. Servien臈 (Nature Research Center), work package leader Dr. L. Kalinien臈. 2015鈥�2018.

During the investigation of the impact of global warming on the diversity and co- evolutionary dynamics between microorganisms and viruses in both Lithuanian and Czech agroecosystems, 39 novel bacteriophages, the majority of which are active against bacteria that belong to the family Enterobacteriacea, have been isolated.The effect of temperature on the efficiency of plating test revealed that two of newly isolated phages, E coli phage NBD2 and Pantoea agglomerans virus Vid5, have a low-temperature plating profile. With an optimum temperature for plating around 20掳C, both phages efficiently produced plaques in a temperature range of 10 to 30掳C, yet failed to plate at temperatures above 35掳C. Since such physiological property proved NBD2 and Vid5 to be of interest in studying the cold-adaptation of viruses, their complete genome sequences were determined and analyzed.

Main publications:

Kaliniene, L., Truncait臈, L., 艩imoli奴nas, E., Zajan膷kauskait臈, A., Vilkaityt臈, M., Kaupinis, A., Skapas, M., Me拧kys, R. Molecular analysis of the low-temperature Escherichia coli phage vB_EcoS_NBD2. Arch. Virol. 2018; 163: 105鈥�114, doi: 10.1007/s00705-017-3589-5.

艩imoli奴nas, E., 艩imoli奴nien臈, M., Kalinien臈, L., Zajan膷kauskait臈, A., Skapas, M., Me拧kys, R., Kaupinis, A., Valius, M., Truncait臈, L. 2018. Pantoea bacteriophage vB_PagS_Vid5: a low-temperature siphovirus that harbors a cluster of genes involved in the biosynthesis of archaeosine. Viruses, vol. 10, p. 583, doi: 10.3390/v10110583.

Research Council of Lithuania. Bacteriophage Control of Nitrogen Cycling in Cyanobacteria: from Cells to Community (No. P-MIP-17-6). Dr. S. 艩ul膷ius (Nature Research Center), work package leader Dr. E. 艩imoli奴nas. 2017鈥�2019.

Filamentous cyanobacteria have an important role in nitrogen cycling in the Baltic Sea, and it could be expected that viruses infecting these cyanobacteria would impact these processes as well. This project aims to evaluate the role of virus infection and lysis on nitrogen metabolism in cyanobacteria and to quantify trophic links and secondary production derived from virus-mediated nitrogen release. During the study, a morphological analysis of cyanophage vB_NodS-kac68v162-1 and cyanophage-mediated dynamics of nodularin and other non-ribosomal peptides in Nodularia spumigena has been performed.

Main publication:

艩ul膷ius, S., Mazur-Marzec, H., Vitonyt臈, I., Kvederavi膷i奴t臈, K., Kuznecova, J., 艩imoli奴nas, E., Holmfeldt, K. 2018. Insights into cyanophage-mediated dynamics of nodularin and other non-ribosomal peptides in Nodularia spumigena. Harmful Algae, vol. 78 p. 69鈥�74, doi: 10.1016/j.hal.2018.07.004.

Research Council of Lithuania. Research on Prediction of Environmental Change in the Baltic Sea Based on Comprehensive (Meta) Genomic Analysis of Microbial Viruses (No. S-LJB-17-1), Dr. S. 艩ul膷ius (Nature Research Center), work package leader Dr. E. 艩imoli奴nas. 2017鈥�2019.

The aim of the project is to investigate the impact of viruses on the cyanobacteria population dynamics in the Baltic Sea. The objectives are: i) analysis of metagenome assembled viral genomes (viral MAG鈥檚) from Baltic Sea metagenome sequencing data, ii) isolation and characterization of new cyanobacteria and cyanophages; iii) assessment of cyanobacteria-cyanophage dynamics in natural and experimental samples. During the study, a cyanophage vB_AphaS-CL131, infecting filamentous diazotrophic cyanobacteria Aphanizomenon flos-aquae, has been characterized using genomic, proteomic and biochemical analysis.

Main publication:

艩ul膷ius, S., 艩imoli奴nas, E., Alzbutas, G., Gasi奴nas, G., Jauni拧kis, V., Kuznecova, J., Sini, S., Nilsson, E., Me拧kys, R., Roine, E., Pa拧kauskas, R., Holmfeldt, K. 2018. Genomic characterisation of cyanophage vB_AphaS-CL131 infecting filamentous diazotrophic cyanobacteria Aphanizomenon flos-aquae reveals novel insights into virus-bacterium interactions. Appl. Environ. Microbiol., vol. 85(1), p. e01311鈥�18, doi:10.1128/AEM.01311-18.

Research Council of Lithuania. The Role of Atmospheric Nitrogen Fixation in the Largest Eutroficated European Lagoon (No. S-MIP-17-7). Dr. M. 沤ilius (Klaip臈da University), work package leader Dr. R. Stanislauskien臈. 2017鈥�2020.

Samples were collected from the two spots of Curonian lagoon every month for the half of year (from April to October). DNA and RNA were extracted from all samples. Later, they will be used for amplification and quantification of nifH genes and its transcripts.

Research Council of Lithuania. Research and Practical Applications of a Type I鈥怓 CRISPR鈥怌as System (No. S-MIP-17-47). Dr. G. Tamulaitien臈 (Institute of Biotechnology, Life Sciences Center, VU), participant - Dr. L. Truncait臈 (Institute of Biochemistry, Life Sciences Center, VU). 2017鈥�2020.

Bacterial immunity systems directed against viral infections have a potential to be developed as the valuable tools for targeted engineering of bacteriophages. In this study, bacterial antiviral systems have been tested for their ability to restrict infections by lytic phages.

Main publication:

Gordeeva, J., Morozova, N., Sierro, N., Isaev, A., Sinkunas, T., Tsvetkova, K., Matlashov, M., Truncaite, L., Morgan, R. D., Ivanov, N. V., Siksnys, V., Zeng, L., Severinov, K. 2018. BREX system of Escherichia coli distinguishes self from non-self by methylation of a specific DNA site. Nucleic Acids Res., doi: 10.1093/nar/gky1125.

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. Me拧kys. 2015鈥�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. Screening systems for hydrolases based on modified uracils or uridines were established by using E. coli strains harboring pyrFEC mutations. Various oxidoreductases and hydrolases have been screened using the metagenomics libraries.

Main publications:

Jakubovska, J., Taurait臈, D., Bir拧tonas, L., Me拧kys, R. 2018. N4-acyl-2'-deoxycytidine-5'-triphosphates for the enzymatic synthesis of modified DNA. Nucleic Acids Res., vol. 46, p. 5911鈥�5923, doi: 10.1093/nar/gky435.

Urbelien臈, N., Kutanovas, S., Me拧kien臈, R., Gasparavi膷i奴t臈, R., Taurait臈, D., Kopl奴nait臈, M., Me拧kys, R. 2018. Application of the uridine auxotrophic host and synthetic nucleosides for a rapid selection of hydrolases from metagenomic libraries. Microb. Biotechnol., doi: 10.1111/1751-7915.13316.

Krik拧taponis, A., Me拧kys, R. 2018. Biodegradation of 7-hydroxycoumarin in Pseudomonas mandelii 7HK4 via ipso-hydroxylation of 3-(2,4-dihydroxyphenyl)-propionic acid. Molecules, vol. 23, p. 2613, doi: 10.3390/molecules23102613.

Jakubovska, J., Taurait臈, D., Me拧kys, R. 2018. A versatile method for the UVA-induced cross-linking of acetophenone- or benzophenone-functionalized DNA. Sci. Rep., vol. 8: 16484, doi:10.1038/s41598-018-34892-9.

Au膷ynait臈, A., Rutkien臈, R., Taurait臈, D., Me拧kys, R., Urbonavi膷ius, J. 2018. Identification of a 2鈥�-O-methyluridine nucleoside hydrolase using the metagenomic libraries. Molecules, vol. 23, 2904, doi:10.3390/molecules23112904.

Patent applications:

Me拧kys, R., Jakubovska, J., Taurait臈, D. N⁴-modified cytidine nucleotides and their use. PCT patent application PCT/IB2018/056961.

Karpus, L., Ma啪elis, I., Rokaitis, I., Jauni拧kis, V., Me拧kys, R. Catalytic biomolecule activity recording into DNA sequence. LT patent application LT2018 542.

Contractual Research

Development of Methods for Elimination of Gliadin-Based Peptides from Protein Mixtures. AB Roquette Amilina, Lithuania. Dr. R. Me拧kys.

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 BIOCHEMISTRY

7 Saul臈tekio, LT-10257 Vilnius
Tel. 223 4392
E-mail:

Head 鈥� Habil. Dr. Narimantas 膶臈nas

STAFF

Chief research fellow: Habil. Dr. N. 膶臈nas.
Senior research fellows: Dr. 沤. Anusevi膷ius, Dr. K. Krik拧topaitis, Dr. J. 艩arlauskas.
Research fellows: Dr. L. Kosychova, Dr. A. Marozien臈, Dr. L. Misevi膷ien臈.
Junior research fellow: E. Polmickait臈-Smirnova.
Doctoral students: B. Valiauga, M. Lesanavi膷ius.

RESEARCH INTERESTS

Investigations of the molecular mechanisms of the antitumour activity and cytotoxicity of aziridinyl-substituted and 鈥搖nsubstituted quinones, in particular the impact of their redox activity on their cytotoxic action
Investigations of the molecular mechanisms of cytotoxicity of novel nitroaromatic compounds, aromatic N-oxides 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, flavo-sulfo, and flavo-sulfo-selenium enzymes possibly participating in the bioreductive activation of quinones and aromatic nitrocompounds and N-oxides

RESEARCH PROJECTS CARRIED OUT IN 2018

Project Supported by University Budget

Molecular Mechanisms of Enzymatic Activation, Detoxification, Biodegradation, and Cytotoxicity of Redox Active Xenobiotics. Habil. Dr. N. 膶臈nas. 2017鈥�2020.

The transhydrogenase reaction studies of Thermotoga maritima thioredoxin reductase (TmTrxR) have shown that the midpoint reduction potential of this enzyme at pH 7.0 is equal to -210 mV. The accumulation of transient flavin semiquinone intermediates during the reduction of quinones by TmTrxR shows that semiquinone oxidation is a rate-limiting step of this reaction. This is supported by the different quinone reduction and transhydrogenase reaction inhibition patterns by NADH, beacuse only two-electron reduced form of TmTrxR but not its semiquinone participates in the later reaction The kinetic characterization of reactions of reactions of Plasmodium falciparum ferredoxin-NADP⁺ reductase (FNR) with quinones were carried out, showing that quinones are more reactive than nitroaromatics with the same single-electron reduction potential values. The transient accumulation of FNR semiquinone and/or its complexes with NADP(H) shows that semiquinone oxidation is the rate-limiting step of reaction. Several novel 1,5-benzodiazepine oxime derivatives were synthesized and characterized by physicochemical methods prior to the studies of their enzymatic reactions.

Main publications:

Rekovi膷, L., Kosychova, L., Bratkovskaja, I., 沤ukauskait臈, V., Vid啪i奴nait臈, R. 2018. Electrochemical characterization of 1,5-benzodiazepine oximes in organic solvents. Chemija, vol. 29, p. 235鈥�242.

Rekovi膷, L., Kosychova, L., Bratkovskaja, I., Vid啪i奴nait臈, R. 2018. Synthesis and spectral characterization of novel 1,5-benzodiazepine oxime derivatives. Journal of the Serbian Chemical Society, 83.

National Research Projects

Research Council of Lithuania: Redox Chemistry, Biochemistry and Cytotoxicity of Aromatic Nitrocompounds and N-Oxides: New Insighths (No. DOTSUT-34/09.33-LMT-K712-01-0058). Habil. dr. N. 膶臈nas. 2018鈥�2021.

The aim of this project is to provide new insights on redox processes and cytotoxicity of aromatic nitrocompounds and N-oxides: i) we found that ascorbate inhibits the oxidation of NADPH by nitroaromatic compounds and E. coli nitroreductase A (NfsA) by a factor of 2, but it does not affect the rates of NADPH:quinone reductase reactions of NfsA. Further analysis revealed that this is attributed to the oxidation of ascorbate by nitroso-intermediates of reaction, which rapidly oxidize NADPH in nonenzymatic way; ii) several derivatives of aromatic di-N-oxide tirapazamine were synthesized, their flavoenzyme-catalyzed single- and two-electron reduction was examined. The compounds proved to be inefficient substrates and inhibitors of human thioredoxin reductases; iii) it was shown that the main factor of cytotoxicity of tirapazamine and its deoxy-metabolites was the oxidative stress.

Main publications:

Valiauga, B., Misevi膷ien臈, L., Rich, M. H., Ackerley, D. F., 艩arlauskas, J., 膶臈nas, N. 2018. Mechanism of two-/four-electron reduction of nitroaromatics by oxygen-insensitive nitroreductases: The role of a non-enzymatic reduction step. Molecules, vol. 23, p. 1672.

艩arlauskas, J., Nemeikait臈-膶臈nien臈, A., Marozien臈, A., Misevi膷ien臈, L., Lesanavi膷ius, M., 膶臈nas, N. 2018. Enzymatic single-electron reduction and aerobic cytotoxicity of tirapazamine and its 1-oxide and nor-oxide metabolites. Chemija, vol. 29, p. 273鈥�280.

International Research Projects

Bilateral Lithuanian-French programme 沤iliberas: Quinones and Nitroaromatic Compounds as Subversive Substrates for Flavohemoglobin: Mechanisms and Biomedical Implications (No. TAP LZ 07/2013). Habil. Dr. N. 膶臈nas. 2013鈥�2014.

A paper on the catalysis mechanism of Staphylococcus aureus flavohemoglobin performed in the frame of this project appeared in 2018:

Main publication:

Moussaoui, M., Misevi膷ien臈, L., Anusevi膷ius, 沤., Marozien臈, A., Lederer, F., Baciou, L., 膶臈nas, N. 2018. Quinones and nitroaromatic compounds as subversive substrates of Staphylococcus aureus flavohemoglobin. Free Radical Biology and Medicine, vol. 123, p. 105鈥�115.

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

Universite de Paris Sud, Orsay (France)
Universite de Strasbourg (France)
Universite de Lorraine, Nancy (France)
Victoria University of Wellington (New Zealand)
Institute of Cell Biology of Ukrainian Academy of Sciences, Lviv (Ukraine)

 

LABORATORY OF BIOORGANIC COMPOUNDS CHEMISTRY

12A Mokslinink懦, LT-08662 Vilnius
Tel. 272 9058
E-mail:

Head 鈥� Dr. Regina Jan膷ien臈

STAFF

Senior research fellows: Dr. R. Jan膷ien臈.
Research fellow: Dr. Z. Staniulyt臈.
Senior specialists: Dr. A. Klimavi膷ius, J. Me拧kauskas, R. Rozenbergas, S. Palaikien臈, D. Pod臈nien臈, Dr. R. Sirutkaitis.

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 2018

Project Supported by University Budget

Investigation of the Synthesis and Structure of Modulators and Catalysts of Biological Processes Dr. R. Jan膷ien臈. 2017鈥�2020.

Synthesis of model pentaethylene glycol (PEG) derivatives bearing different 伪- and 蠅-substituents. The possibility to synthesize pentaethylene glycol derivatives bearing different 伪- and 蠅-substituents at terminal chain positions was studied. The synthesis scheme was developed for 伪-amino-PEG-蠅-alkylsulphonic acid derivatives. Mono-amino-PEG was used as starting compound for this synthesis. Mono-amino-PEG was prepared via sequence of 3 reactions: (1) synthesis of monomesyl-PEG, (2) synthesis of PEG monoazide, (3) reduction of azide group with triphenylphosphine to amino group. The alkylation reaction with butan-1,4- and propan-1,3-sultones was used with the aim to introduce alkylsulphonic acid moiety. In the study of this reaction, conditions of hydroxy group alkylation reaction were established and model PEG bisalkylsulphonates were synthesized. On the basis of this investigation and established alkylation conditions of monoamino-PEG with sultones, PEG-derivatives bearing 伪-amino and 蠅-alkylsulphonic acid moiety were synthesized.

Synthesis of mono- and di-substituted cyclic polyethers and purification methods. In continuation of our study on the synthesis of cyclic polyethers containing cyclohexane fragments, the conditions for the catalytic hydrogenation of dibenzo-18-crown-6 (DB18K6) and 4,4(5'-di-tert-butyl-dibenzo-18-crown-6 (t-BuDCH18K6) in high-pressure autoclaves were optimized by changing various parameters: catalysts, solvents, temperature, pressure, and the ratio of catalyst and substrate. Experimental technologies of the catalytic hydrogenation were created based on the obtained results. Study of mono-substituted cyclic polyethrs was started. A new alternative, synthetically-viable route to benzo-18-crown-6 was also developed and tested. The six-oxygen benzo crown ether was obtained in a yield of 30鈥�55% by the interaction of 1,2-bis(2-hydroxyethoxy)benzene with triethylene glycol dimesylate. To optimize the yield of benzo crown, various modifications of the reaction conditions were studied and it was found that the condensation of diol and dimesylate under the conditions of phase transfer catalysis gives the best result.

Investigation and optimization of synthesis methods of fluorescence indole derivatives. In order to optimize the synthesis of 2-(4-amidinophenyl)-6-indolocarbamidine dihydrochloride (DAPI), the possibility of creating an indole ring by thermal cyclization of unsaturated intermediates was investigated. This study allowed to exclude the laborious step of reductive heterocyclization of compounds having nitro and carbonyl groups from the multistage synthesis scheme of the target DAPI. It was found that the condensation of 4-methyl-3-nitrobenzonitrile and 4-cyanobenzaldehyde yielded 40鈥�50% of 4-[(E)-2-(4-cyanophenyl)vinyl]-3-nitrobenzonitrile. Modification of the reaction conditions did not allow increasing the yield of vinyl derivative, but compared to the previous process, the synthesis scheme was reduced by one step. 2-(4-Cyanophenyl)-1H-indole-6-carbonitrile was synthesized by reacting the vinyl compound with triphenylphosphine in a solution of boiling tetrahydronaphthalene and, after a single crystallization, was further used for the synthesis of DAPI. Yield of indole derivative was an average of 30鈥�40%.

Contractual Research

Study of Synthesis Optimization of Pantetine-4,4-Diphosphate and Other Enzyme Cofactors. Contract with UAB Thermo Fisher Scientific Baltics. Dr. R. Jan膷ien臈.

Investigation of Regeneration Conditions of Butylacetate and Negative Developer and Manufacturing of their Experimental Batches. Contract with UAB Vilniaus Ventos puslaidininkiai. Dr. A. Klimavi膷ius.

Research In Development of New Methods for Making Long Polyethylene Glycols by Reacting Polyethyleneglycol-Dimesylates with Excess Triethylene Glycol. Contract with Ramidus AB (Sweden). Dr. R. Jan膷ien臈.

Development of Viable Methods for the Synthesis of Various Organic Compounds and Preparation of their Experimental Batches. Contract with Synthon Chemicals Gmbh (Germany). Dr. R. Jan膷ien臈.

Analysis of New Lipase Immobilizing Sorbents. Contract with UAB Ekorama. Dr. R. Jan膷ien臈.

Study of the Synthesis of 3,6-Dichloro-s-Tetrazine. Contract with UAB Certumtech. Dr. R. Jan膷ien臈.

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

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

 

PROTEOMICS CENTRE

7 Saul臈tekio, LT-10257, Vilnius
Tel. 223 4410
E-mail:

Head 鈥� Dr. Mindaugas Valius

STAFF

Senior research fellows: Dr. M. Valius, Dr. J. Cic臈nas.
Research fellows: Dr. A. Kaupinis, Dr. M. Ger.
Doctoral students: N. Drei啪臈, S. Urnikyt臈, E. 沤alyt臈, G. Karzait臈, I. Me拧kinyt臈.

RESEARCH INTERESTS

High throughput proteomics analysis of cell signalling
Elucidation of artificial microstructures and nano particles on cell functioning
Biomarkers for cancer diagnostics and treatment
Investigation of mechanisms of cancer cell resistance to chemotherapy

RESEARCH PROJECTS CARRIED OUT IN 2018

Project Supported by University Budget

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

Main publications:

Rynkeviciene, R., Simiene, J., Strainiene, E., Stankevicius, V., Usinskiene, J., Miseikyte Kaubriene, E., Meskinyte, I., Cicenas, J., Suziedelis, K. 2018. Non-coding RNAs in glioma. Cancers (Basel), vol. 11(1), doi:10.3390/cancers11010017.
Cicenas, J., Zalyte, E., Bairoch, A., Gaudet, P. 2018. Kinases and cancer. Cancers (Basel), vol. 10(3), pii: E63, doi: 10.3390/cancers10030063.
艩imoli奴nas, E., 艩imoli奴nien臈, M., Kaliniene, L., Zajan膷kauskait臈, A., Skapas, M., Me拧kys, R., Kaupinis, A., Valius, M., Truncait臈, L. 2018. Pantoea bacteriophage vB_PagS_Vid5: a low-temperature siphovirus that harbors a cluster of genes involved in the biosynthesis of archaeosine. Viruses, vol. 10(11), pii: E583.
Korabliovien臈, J., Mauricas, M., Ambrozevi膷ien臈, 膶., Valius, M., Kaupinis, A., 膶aplinskas, S., Korabliov, P. 2018. Mycobacteria produce proteins involved in biofilm formation and growth-affecting processes. Acta Microbiol Immunol Hung, vol. 65(3), p. 405鈥�418, doi: 10.1556/030.65.2018.033.
Kaliniene, L., Truncait臈, L., 艩imoli奴nas, E., Zajan膷kauskait臈, A., Vilkaityt臈, M., Kaupinis, A., Skapas, M., Me拧kys, R. 2018. Molecular analysis of the low-temperature Escherichia coli phage vB_EcoS_NBD2. Arch Viro, vol. 163(1), p. 105鈥�114, doi: 10.1007/s00705-017-3589-5.

National Research Projects

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鈥�2018.

In this project, we have performed high throughput quantitative proteomic analysis of the chemotherapy鈥恠ensitive and 鈥恟esistant colorectal cancer (CRC) cell lines. Potential predictive biomarkers for FOLFOX therapy have been identified and currently undergoing validation on clinical material. Novel TP53 mutations have been discovered in the oxaliplatin-resistant cells that likely contribute to the drug resistance.

Research Council of Lithuania. New Multifunctional Nanobiosensor for Early Pancreatic Cancer Diagnostics (No. SEN-16041). Project manager Prof. K. Strupas, work package manager Dr. M. Valius. 2015鈥�2018.

We perform high-throughput protein biomarkers discovery using already collected as well as collected in the frame of this project patients鈥� pancreatic material. The potential biomarkers have been discovered and now undergoing validation on patients鈥� surgical material. A novel multifunctional prototypical analytical system based on protein biomarkers detection with antibody-coated quantum dots and magnetic particles have been designed, fabricated and now is undergoing laboratory tests.

Main publication:

Ger, M., Kaupinis, A., Petrulionis, M., Kurlinkus, B., Cicenas, J., Sileikis, A., Valius, M., Strupas, K. 2018. Proteomic identification of FLT3 and PCBP3 as potential prognostic biomarkers for pancreatic cancer. Anticancer Res, vol. 38(10), p. 5759鈥�5765, doi:10.21873/anticanres.12914.

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)
91桃色 Hospital Santaros Klinikos, Vilnius (Lithuania)
Nation Center of Patology, Vilnius (Lithuania)
Lithuanian University of Health Science, Institute of Cardiology, Kaunas (Lithuania)

OTHER SCIENTIFIC ACTIVITIES

Dr. M. Valius 鈥�

• editorial board member of the journal MAP Kinases;
• reviewer for PlosONE.

Dr. J. Cic臈nas 鈥�

• collection editor of the Kinases and Cancer.
  
  

INSTITUTE OF BIOSCIENCES

7 Saul臈tekio, LT-10257 Vilnius
Tel. 239 8200, fax 239 8204
E-mail:
www

Director 鈥� Prof. Habil. Dr. Juozas Lazutka

DEPARTMENTS OF THE INSTITUTE

Department of Biochemistry and Molecular Biology
Department of Botany and Genetics
Department of Microbiology and Biotechnology
Department of Neurobiology and Biophysics
Department of Zoology
Centre for Ecology and Environmental Research

RESEARCH AREAS

Genomics, Biomolecules and Biotechnologies: Fundamental and Applied Research
Ecosystems and Climate Changes, Preservation of Environment and Use of Natural Resources
Investigation of Nervous System and Behaviour

DOCTORAL DISSERTATIONS MAINTAINED IN 2018

M. Baranauskas. Associations of brain electrical activity with heart rate regulation and body awareness.
I. Buchovec. Inactivation of food pathogens by photoactivated Chlorophyllin: mechanism of action, optimization and possible applications.
A. Kaunietis. Identification, heterologous biosynthesis and characterization of novel bacteriocins from thermophilic bacteria.
A. Konovalovas. Molecular determinants of Totiviridae family viruses of Saccharomyces sensu stricto clade.
A. Stumbryt臈 Human papillomavirus and the gene polymorphism involved in tumorogenesis effects on laryngeal and lung cancer patients鈥� survival.
A. Mlynska The role of systemic and local immunity in tumour development and response to treatment.
R. Grigonis Response properties of motoneurons during spinal neural network activity.

MAIN CONFERENCES ORGANIZED IN 2018

10th conference of the Lithuanian Neuroscience Association (LNA)
2nd international symposium on Visual Physiology, Environment, and Perception (VisPEP 2018) The COINS 2018

MOST IMPORTANT NATIONAL AND INTERNATIONAL AWARDS RECEIVED FOR R&D ACTIVITIES

Urt臈 Neni拧kyt臈. Young Scientist Award by Lithuanian Science Academy

MOST IMPORTANT PARTICIPATION CASES OF RESEARCHERS IN WORKING GROUPS OR COMMISSIONS SET UP BY STATE AUTHORITIES, STATE AND MUNICIPAL INSTITUTIONS AND ORGANISATIONS, AND BUSINESS ENTITIES

Urt臈 Neni拧kyt臈. Committee member at Young Division of International Brain Research Organization; Board member of Lithuanian Research Council

Osvaldas Ruk拧臈nas. Member of FENS (Federation of Neuroscience Societies) Board

Inga Gri拧kova-Bulanova International Brain Research Organization Governing Council member

Ernestas Kutorga. Member of the Invasive Species Control Council of the Ministry of Environment of the Republic of Lithuania.
Member of the Lithuanian Red Data Book Commission of the Ministry of Environment of the Republic of Lithuania.

CONSULTATIONS PROVIDED BY THE UNIT TO THE PUBLIC OR ECONOMIC ENTITIES

Consultations on the identification and use of plants, fungi and lichens. Nature protection, forestry and agriculture specialists, naturalists and other individuals have been consulted by scientists of Botany and mycology group.
Scientific practical conference of toxicologists Praktin臈 toksikologija (Practical toxicology), April 12, Vilnius. Oral presentation: Valgomieji ir nuodingieji grybai: po啪ymiai ir identifikavimas (Edible and poisonous fungi: characters and identification) by E. Kutorga.

MOST IMPORTANT RESEARCH DISSEMINATION ACTIVITIES

Neni拧kyt臈 U. Scientific outreach program "Mokslo sriuba" on "How does the brain work?"
Scientific outreach program "paMOKSLAS" on "Brain: what is it?"
Ruk拧臈nas O. Interview for the journal Moteris, August 2018
National TV program Cultural Crossroads
National radio program Radio afternoon
Interview for the news portal Delfi
Panel discussion Human modifications: where is the limit? at the international conference of Life Sciences, The COINS 2018, February 28, Vilnius, Lithuania
Gri拧kova-Bulanova I. Interview for the news portal Delfi

Department of Microbiology and Biotechnology:
National science festival Erdv臈laivis 沤em臈 (Spaceship Earth) - International Microorganisms Day, whole day event for education in microbiology

Lastauskien臈 E. Interview for the National radio program 鈥淢okslas kuria pasaul寞鈥�;
3 Interviews for the National TV program TV3 News;
Project Vaik懦 universitetas (Children鈥檚 University) 鈥� Microorganisms 鈥� friends or enemies?

Kleizait臈 V., 沤vingila D. Interview for the journal Literat奴ra ir menas, Paslaptingas up臈s augal懦 gyvenimas.

Butkuvien臈 J. Interview for the news portal DELFI 沤mon臈s 鈥� upi懦 ekosistemos dalis: kod臈l ne visi baidarininkai to paiso?

沤vingila D. Interview for the National TV program Projektai, Mano aplinka. Geneti拧kai modifikuot懦 mikroorganizm懦 riboto naudojimo veikla Lietuvoje.

Department of Zoology
1) Guided tours and educational tours in the Vilnius university Museum of Zoology;
2) participation in annual festival Culture Night, in annual national science festival Spaceship Earth, Researcher鈥檚 Night, European Night Museum;
3) exhibitions: Golden Trace of Dino Zauro specially for the 50th Physics鈥� Day (FiDi) dedicated to VU alumni, physicist Gediminas Vaitiek奴nas, VU Zoology museum patronage Professor Ri膷ardas Kazlauskas
4) Partner - exhibit lender for exhibition, organized by Lithuanian Art Museum: Pilies Street Vilnius Picture Gallery, 4 Did啪ioji St, Vilnius,
5) Interview and consultations for Lithuanian Radio program Ryto garsai,
鈥�
DEPARTMENT OF BIOCHEMISTRY AND MOLECULAR BIOLOGY

STAFF

Professors: Dr. E. Su啪ied臈lien臈, Dr. S. Serva, prof. V. Starkuvien臈 (part-time). K. Su啪ied臈lis (part-time).
Associate professors: Dr. D. Dabkevi膷ien臈, Dr. A. Markuckas, Dr. A. Sasnauskien臈, Dr. A. Zimkus, Dr. V. Jonu拧ien臈, Dr. D. Labeikyt臈.
Lecturer: Z. 沤itkus.
Senior research fellows: Dr. J. Armalyt臈, Dr. A. Zimkus.
Research fellows: Dr. V. Jonu拧ien臈, Dr. A. Sasnauskien臈, Dr. D. Labeikyt臈.
Junior research fellow: A. Konovalovas.
Doctoral students: E. Kukcinavi膷i奴t臈, J. Skerni拧kyt臈, A. Mikalk臈nas, J. Fadejeva, L. Kunig臈nas, L. Aitmanait臈, R. Krasauskas, V. 沤itkut臈.

RESEARCH INTERESTS

Molecular determinants of virus cycle. Antivirals
Biochemical mechanisms of cellular response to photooxidation and cytotoxic treatment
Bacterial stress responses, pathogenesis, antibiotic resistance

RESEARCH PROJECTS CARRIED OUT IN 2018

Projects Supported by University Budget

Investigation of Mechanisms of Cellular Homeostasis and Their Clinical and Biotechnological Application. Prof. Dr. E. Su啪ied臈lien臈, Prof. Dr. S. Serva, Assoc. Prof. A. Sasnauskien臈.

Investigation of biochemical mechanisms and components conferring resistance of viruses, bacterial and eukaryotic cells against antiviral, antibacterial and anticancer compounds: 1) cellular response to anti-cancer treatment, cellular and molecular mechanisms of acquired chemoresistance, the role of autophagy and changes in growth factors and cytokine expression; 2) molecular mechanisms of antibiotic resistance and microbial pathogenesis of gram-negative bacterial pathogens with the emphasis on the novel antibacterial targets and bacterial toxin-antitoxin systems, development of molecular techniques for detection of antibiotic resistant bacteria; 3)research on yeast dsRNA viruses and nucleoside/nucleotide based antivirals for retroviruses.

Main publications:

Grybchuk, D., Akopyants, N. S., Kostygov, A.Y., Konovalovas, A., Lye, L. F., Dobson, D. E., Zangger, H., Fasel, N., Butenko, A., Frolov, A. O., Vot媒pka, J., d'Avila-Levy, C. M., Kulich, P., Moravcov谩, J., Plevka, P., Rogozin, I. B., Serva, S., Luke拧, J., Beverley, S. M., Yurchenko V. 2018. Viral discovery and diversity in trypanosomatid protozoa with a focus on relatives of the human parasite Leishmania. Proc Natl Acad Sci U S A, doi: 10.1073/pnas.1717806115.
Mikalk臈nas, A., Ravoityt臈, B.,Taurait臈, D., Servien臈, E., Me拧kys, R., Serva, S. 2018. Conjugation of phosphonoaceticacid to nucleobase promotes a mechanism-based inhibition. Journal of Enzyme Inhibition and Medicinal Chemistry. 2018, doi: 10.1080/14756366.2017.1417275.
Armalyt臈, J., Jur臈nas, D., Krasauskas, R., 膶epauskas, A., Su啪ied臈lien臈, E. The higBA toxin-antitoxin module from the opportunistic pathogen Acinetobacter baumannii - regulation, activity, and evolution. Front Microbiol. 2018, doi: 10.3389/fmicb.2018.00732.

National Research Projects

Research Council of Lithuania. Influence of Intensive Farming on the Emergence, Persistence and Spread of Antibiotic and Biocide-Resistant Bacteria in Soil and Water (Nr. SIT-15013). Dr. J. Armalyt臈. Project leader Dr. M. Ru啪auskas. 2015鈥�2018.

Research Council of Lithuania. New Markers for Personalized Therapy of Colorectal Cancer: Proteomics, Genomics, Clinic. Dr. A. Sasnauskien臈, Dr. V. Jonu拧ien臈. Project leader prof. A. Laurinavi膷ius. 2015鈥�2018.

Main publication:

Kukcinaviciute, E., Jonusiene, V., Sasnauskiene, A., Dabkeviciene, D., Eidenaite, E., Laurinavicius, A. 2018. Significance of Notch and Wnt signaling for chemoresistance of colorectal cancer cells HCT116. J Cell Biochem, doi: 10.1002/jcb.26783.

Research Council of Lithuania. Microbiota of Agrosystems under Changing Climate Conditions: Structure and Modus Mechanisms. Dr. S. Serva, A. Konovalovas. Project leader E. Servien臈. 2015鈥�2018.

Main publication:

Vep拧tait臈-Monstavi膷臈, I., Luk拧a, J., Konovalovas, A., E啪erskyt臈, D., Stanevi膷ien臈, R., Strazdait臈-沤ielien臈, 沤., Serva, S., Servien臈, E. 2018 .Saccharomyces paradoxus K66 killer system evidences expanded assortment of helper and satellite viruses. Viruses, doi: 10.3390/v10100564.

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

Lithuanian University of Health Sciences (Lithuania)
Nature Research Centre (Lithuania)
Heidelberg University (Germany)
University of Ostrava, Czech Republic.
Universite Libre de Brussels (Belgium)
University of Haifa (Israel)

OTHER SCIENTIFIC ACTIVITIES

Prof. E. Su啪ied臈lien臈 鈥�

• member of Research Council of Lithuania (2018鈥�2022).

Prof. S. Serva 鈥�

• council member of the Lithuanian Biochemical Society;
• member of Biomedical and Agricultural Expert Board at Lithuanian Agency for Science, Innovation and Technology.

 

DEPARTMENT OF BOTANY AND GENETICS

7 Saul臈tekio, LT-10257 Vilnius
Tel. 239 8257
E-mail:
Head 鈥� Prof. Habil. Dr. Juozas Lazutka

STAFF

Professors: Dr. S. Jarmalait臈, Dr. E. Kutorga, Dr. A. Lubys (part-time), Habil. Dr. J. R. Naujalis, Habil. Dr. I. Pa拧akinskien臈 (part-time), Habil. Dr. V. Ran膷elis (emeritus), Dr. G. Slap拧yt臈, Dr. D. 沤vingila.
Associate professors: Dr. T. 膶臈snien臈, Dr. J. Kostkevi膷ien臈, Dr. V. Mork奴nas (part-time), Dr. R. 艩iuk拧ta (part-time), Dr. K.Dani奴nait臈 (part-time), dr. V.Dedonyt臈 (part-time).
Assistants: Dr. I. Prigodina Luko拧ien臈.
Junior assistants: P. Venckus, A. Stapulionyt臈, K. Stuopelyt臈.
Lecturers: S. Juz臈nas, A. Meld啪iukien臈, Dr. E. Me拧kauskait臈.
Senior research fellow: Dr. V. Kleizait臈.
Research fellows: Dr. V. Dedonyt臈 (part-time), Dr. J. Mierauskien臈, Dr. V. Mork奴nas (part-time), Dr. D. Naug啪emys, Dr. J. Patamsyt臈, Dr. V. Vaitk奴nien臈, Dr. J. Butkuvien臈, Dr. R. 艩iuk拧ta (part-time), Dr. K. Dani奴nait臈 (part-time), Dr. R. Rimgail臈-Voicik.
Junior research fellow: M. Rasimavi膷ius.
Senior biologist: Dr. J. Ruk拧臈nien臈.
Doctoral students: A. Nestarenkait臈, G. Rad啪iuvien臈, I. Sadzevi膷ien臈, 沤. Kapustina, R. Kubili奴t臈, D. Strepetkait臈, L. 艩iaulien臈, D. 沤alimas, D, Uljanionok, J. Sejonien臈.

RESEARCH INTERESTS

Search and application of the most effective biomarkers for genetic monitoring of human, animal and plant populations
Investigation of mutagenic and antimutagenic effects of chemical compounds in human cells in vitro and experimental model systems in vivo
Analysis of epigenetic changes in human malignancies
Studies of DNA polymorphism in plant populations
Plant developmental, population genetics and phylogenetics
Plant, algae and fungal species diversity, systematics, sociology, biology, ecology and distribution.
Research and monitoring of rare, protected and alien plant and fungal species
Algal biotechnology
Composition, structure and dynamics of lichen and plant populations
Studies of historical fungal, algae, lichen and plant collections, maintained in the Herbarium of 91桃色

RESEARCH PROJECTS CARRIED OUT IN 2018

Projects Supported by University Budget

Function, Variability and Genome Structure in Higher Eukaryotes. Prof. J. R. Lazutka, Prof. G. Slap拧yt臈, Prof. S. Jarmalait臈. 2014鈥�2018.

Genotoxicity and antioxidant activity of extracts prepared from five Agrimonia and Filipendula species, traditionally used in folk medicine as anti-inflammatory herbs, was evaluated using alkaline single-cell gel electrophoresis (Comet) and micronucleus assays in human lymphocytes in vitro and Ames Salmonella/microsome test. All investigated Agrimonia and Filipendula extracts possessed strong antioxidant activity, they were not mutagenic in the Salmonella/microsome and micronucleus tests, but induced DNA damage evaluated by the Comet assay at high concentrations. We propose that tested Agrimonia and Filipendula species are relatively safe and have good potential for use in food industry and natural medicine, however concentration has to be evaluated.
DNA methylation and gene expression were analyzed in circulating tumor DNA.

Main publications:

Pukalskien臈, M., Slap拧yt臈, G., Dedonyt臈, V., Lazutka, J.R., Mierauskien臈, J., Venskutonis, P.R. 2018. Genotoxicity and antioxidant activity of five Agrimonia and Filipendula species plant extracts evaluated by comet and micronucleus assays in human lymphocytes and Ames Salmonella/microsome test. Food and Chemical Toxicology, vol. 113, p. 303鈥�313, doi: 10.1016/j.fct.2017.12.031.

Daniunaite, K., Jarmalaite, S., Kriukiene, E. 2018. Epigenomic technologies for deciphering circulating tumor DNA. Curr Opin Biotechnol., vol., p. 23鈥�29, doi: 10.1016/j.copbio.201 8.07.002.

Plant Polymorphism, Genome Stability and its Changing Factors. Prof. Emeritus V. Ran膷elis, Prof. D. 沤vingila. 2016鈥�2020.

Genetic polymorphism is very important in the situation of the global climate change and is exploited in plant species conservation and breeding. We studied the natural and induced plant genome variability using genetic, biochemical, statistical and bioinformatical methods. Analysis of rDNA ITS region showed that Potamogeton assidens and P. nerviger are hybrid forms of P. perfoliatus and P. nodosus. Further studies were carried out on the analysis of barley homeotic mutants and the role of phytohormones in the development of floral organs was investigated. The results of the present study linked the genetic instability of homeotic double mutants with an auxin imbalance in plant tissues. Informative CDDP primers (WRKY-R3, MYB1, ERF3, KNOX3, ABP1-3) were selected for investigation on the Lithuanian spring barley cultivars. The highest level of DNA polymorphism was observed in cv. 'Luok臈' (50.7%), what may reflect its ability to grow in a wide range of environmental conditions. The average level of polymorphism in the investigated cultivars was 22.8%.

Main publications:

艩iuk拧ta, R., Vaitk奴nien臈, V., Ran膷elis, V. 2018. Is auxin involved in the induction of genetic instability in barley homeotic double mutants? Planta, vol. 247(2), p. 483鈥�498, doi: 10.1007/s00425-017-2802-9.

Patamsyt臈, J., Naug啪emys, D., 膶臈snien臈, T., Kleizait臈, V., Demina, O.N., Mikhailova, S.I., Agafonov, V.A., 沤vingila, D. 2018. Evaluation and comparison of the genetic structure of Bunias orientalis populations in their native range and two non-native ranges. Plant Ecology, vol. 219, p. 101鈥�114, doi: 10.1007/s11258-017-0781-3.

The Structure, Functioning in Ecosystems and Conservation of Vegetation, Algobiota and Mycobiota. Prof. J. R. Naujalis, Prof. E. Kutorga. 2014鈥�2018.

Microalgae pigment scytonemin is known as sunscreen sheath enclosing the cells against ultraviolet radiation. The chemically specific coherent anti-Stoke Raman spectroscopy (CARS) response from particular chemical compounds in the algae cell is usually weak because of their low concentration and often are overwhelmed by optical emissions from other cellular constituents. We demonstrated that for scytonemin localized in cyanobacteria Nostoc commune, the vibrational response is sufficient for its reliable identification.
In 2018, the study of the 19th century collection of bryophytes in the Herbarium of 91桃色 (WI) was summarised. The analysis of handwriting on specimen labels, as well as their style, showed that more than half of the collection had been compiled by S.T. Gorski. It was found that S.T. Gorski鈥檚 reassembled bryological collection at WI contains 729 specimens of bryophytes. The analysis and overview of A. Minkevi膷ius contribution to the knowledge on bryophyte diversity, distribution and ecology in Lithuania was done.
Investigations on residual effect of induced water stress and nitrogen addition on the mycobiota in Scots pine stands were summarized. The results demonstrate that both artificial drought and nitrogen addition lead to decrease of fungal species in general, however, responses of individual trophic and ecological groups varied. The strongest effect of the treatments was observed for soil fungi, especially mycorrhizal species.

Main publications:

Venckus, P., Paliulis, S., Kostkevi膷iene, J., Dementjev, A. 2018. CARS microscopy of scytonemin in cyanobacteria Nostoc commune. Journal of Raman Spectroscopy, vol. 49(8), p. 1333鈥�1338, doi: 10.1002/jrs.5388.

Jukonien臈, I., Rasimavi膷ius, M., Ri膷kien臈, A., Subkait臈, M. 2018. S. B. Gorski鈥檚 bryological collection in the Herbarium of 91桃色. Acta Societatis Botanicorum Poloniae, vol. 87(3), p. 3588, doi:

Motiej奴nait臈, J., Buo啪yt臈, R., Adamonyt臈, G., Ir拧臈nait臈, R., Kasparavi膷ius, J., Kutorga, E., Markovskaja, S., Stak臈nas,V., Klyukina E. 2018. Residual effect of induced water stress and nitrogen addition on the mycobiota in Scots pine stands. Russian Journal of Ecology, vol. 49(3), p. 226鈥�231, doi: 10.1134/S1067413618030050.

National Research Projects

Research Council of Lithuania. Use of Molecular and Cytogenetic Markers to Assess Permanent Genotoxicity of Ecologically Dangerous Soils. (No. MIP 042-15). Assoc. prof. T. 膶臈snien臈. 2015鈥�2018.

Currently, application of molecular markers is emerging in studies of genotoxicity and response to environmental factors. In order to adopt new markers in the study of polluted territories it is essential to compare their effectiveness with the traditionally approved methods of environmental genotoxicology. Comparison of cytogenetic and molecular markers is used to assess the effect of genotoxic compounds in soil samples collected from areas with different type and level of pollution and intensive human activity areas. Polluted-soil-induced oxidative stress was evaluated using Tradescantia clone 4430, employing biochemical (superoxide dismutase (SOD), contents of ascorbic acid (AA), carotenoids (Car), hydrogen peroxide (H2O2), chlorophyll a/b ratio, and molecular (RAPD and differential display (DD-PCR)) markers after long-term exposure, and changes in genomic DNA and gene expression patterns were detected.

Main publication:

艩iuk拧ta, R., Bondzinskait臈, S., Kleizait臈, V., 沤vingila, D., Tara拧kevi膷ius, R., Mockeli奴nas, L., Stapulionyt臈, A., Mak, K., 膶臈snien臈, T. 2018. Response of Tradescantia plants to oxidative stress induced by heavy metal pollution of soils from industrial areas. Environmental Science and Pollution Research, doi: 10.1007/s11356-018-3224-3.

Research Council of Lithuania. Human Impact on Stability of Vegetation in Chosen River Ecosystems in Lithuania. (No. SIT-02/2015). Prof. D. 沤vingila. 2015鈥�2018.

SIT-2/2015 project is aimed at evaluation of influence of anthropogenic factors on stability of vegetation as the core component of water ecosystems. Three partners (VU 鈥� leading institution, NRC and MDU) collaborates in this project. During execution of the project recreation activity, stream way modification and incoming chemical pollution effects will be analyzed employing parameters of genetic diversity, genetic structure of populations and ecological adaptation of ten plant species representing main aquatic niche.

Main publications:

Vy拧niauskien臈, R., Ran膷elien臈, V., Naug啪emys, D., Patamsyt臈, J., Sinkevi膷ien臈, Z., Butkuvien臈, J., 沤vingila, D. 2018. Genetic diversity of populations of Bidens genera invasive and native species in Lithuania. Zemdirbyste-Agriculture, vol. 105, p. 183鈥�190, doi: 10.13080/z-a.2018.105.024.

Butkuvien臈, J., Sinkevi膷ien臈, Z., Naug啪emys, D., 沤vingila, D. 2018. Floristic structure of two Batrachium rich plant communities in relation to habitat conditions in rivers of Lithuania. Polish Journal of Ecology, vol. 66, p. 1鈥�13, doi: 10.3161/15052249PJE2018.66.1.001.

Research Council of Lithuania. Impact of Clear Cuttings on Transformation of Biodiversity in Forest Ecosystems (MEKODINA), No. SIT-1/2015. Participants of project Dr. E. Me拧kauskait臈, S. Juz臈nas, Dr. R. Rimgail臈-Voicik, A. Meld啪iukien臈. 2015鈥�2018.

The aim of the project was to investigate the dynamics of a forest鈥檚 soil chemical composition and variation of ground vegetation and insects鈥� diversity. Various methods of agrochemistry, entomology, chemistry, and geobotany were applied in order to determine the impact of clear-cuttings on a forest鈥檚 ecosystem components. Scientific-practical outcomes of the project were published in a book of recommendations for forest managers.

Main publication
Daubaras, R., 膶esonien臈, L., Stak臈nas, V., Tamutis, V., Ka拧konien臈, V., Zych, M., Juz臈nas, S. 2018. Plyn懦j懦 kirtim懦 poveikis pu拧yn懦 ekosistemoms ir b奴dai joms stabilizuoti: mokslin臈s-praktin臈s rekomendacijos (Impact of clear-cuttings on a pine forest ecosystems and ways to stabilize them: scientific-practical recommendations). Kaunas: Vytauto Did啪iojo universitetas, 30 p., doi: 10.7220/9786094673603.

Research Council of Lithuania. Unstudied Bryophyte Collections. Significance of the Assessment of Lithuania Bryoflora Structure and the Impact of Landscape Changes on It. No. LIP-100/2016. Participant of project: Dr. M. Rasimavi膷ius. 2016鈥�2018.

During the project, bryophyte collections of the end of 19th century till the middle of the 20th century were investigated. Their significance for bryophyte diversity in Lithuania was assessed. The specimens of the collections were identified and inserted into the main Herbaria to ensure their accessibility for the future scientific investigations. The results of project were presented in a book:

Main publication

Jukonien臈 I. (comp.). Briologiniai archyvai 鈥� Lietuvos mokslo ir gamtos istorijos paveldas (Bryological archives 鈥� Lithuanian heritage of science and nature history). Vilnius, Gamtos tyrim懦 centras, 168 p.

Ministry of Environment of Republic of Lithuania. Preparation of the edition Red Data Book of Lithuania. Participants from VU: Dr. E. Kutorga, Habil. Dr. J.R. Naujalis, Dr. I. Prigodina Luko拧ien臈, Dr. M. Rasimavi膷ius.

During the project in 2018, protected in Lithuania plant, fungal and lichen species were reassessed according International Union for Conservation of Nature (IUCN) Red List categories and criteria. For all treated species the data on their distribution, biology, ecology, population and threat status, and conservation measures were provided for publishing in a forthcoming new edition of Red Data Book of Lithuania.

Research Council of Lithuania. Modern Technologies to Resolve a Complex Structure of Tumour (No. P-MIP-17-189). Prof. S. Jarmalait臈. 2017鈥�2020.

The main objective of the present study is to investigate the intrinsic and extrinsic complexity of renal and pulmonary tumours for improved understanding of molecular mechanisms of cancer development and progression. Genomic profile cellular subclones from the same renal tumour has been analysed in order to resolve intratumoral and extratumoral heterogeneity of cancer and understand clinical consequences of genetic complexity of tumour.

Research Council of Lithuania. Molecular Tools for Prostate Cancer Follow-up and Treatment Individualization (No. SEN-9/2016). Prof. F. Jankevi膷ius. 2016鈥�2018.

Modern genomic techniques for DNA methylation (metDNA) and gene expression (GE) analysis have been adapted to identify molecular biomarkers of castration-resistant prostate cancer (CRPC). Comparison of CRPC, indolent PCa, and histologically normal prostate tissues revealed numerous differences in metDNA and GE profiles among the groups. Our results show that selected PCa-specific (epi)genetic changes detectable in blood or urine from CRPC patients can reflect responsiveness to therapy and are valuable as biomarkers for treatment individualization.

Contractual Research

Research project sponsored by Joint-stock company 鈥淔ortum Klaip臈da鈥�. Cultivation of Algae Haematococcus Pluvialis and Optimization of Dry Biomass Exclusion. No: TPS-600000-1761. Participant of project P. Venckus. 2017鈥�2018.

The aim of the project was the optimization of cultivation and biomass exclusion of astaxanthin-rich greenalgae Haematococcus pluvialis biomass.

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

Nature Research Centre (Lithuania)
Vytautas Magnus University (Lithuania)
National Cancer Institute (Lithuania)
Institute for Ecosystem Studies (Florence, Italy)
Prostate Cancer Research Centre, University of Tampere (Finland)
Department of Pathology, University of Helsinki
HUSLAB, Helsinki University Hospital (Finland)

OTHER SCIENTIFIC ACTIVITIES

Prof. V. Ran膷elis 鈥�

• ditorial board member of the journal Ecological Genetics (Russian Academy of Sciences);
• member of the Lithuanian Academy of Sciences.

Prof. E. Kutorga 鈥�

• editor of the journal Botanica Lithuanica;
• editorial board member of the journal Folia Cryptogamica Estonica;
• editorial board member of the journal Acta Mycologica;
• editorial board member of multivolume edition Lietuvos grybai (Mycota Lithuaniae).

Prof. J. R. Naujalis 鈥�

• editorial board member of the journal Biologija;
• editorial board member of the journal Scripta Horti Botanici Universitatis Vytauti Magni;
• full member of the Lithuanian Academy of Sciences.

Prof. J. R. Lazutka 鈥�

• deputy editor-in-chief of the journal Biologija;
• editor of the journal Open Life Sciences;
• editorial board member of the journal Ecological Genetics (Russian Academy of Sciences).

鈥�
DEPARTMENT OF MICROBIOLOGY AND BIOTECHNOLOGY

7 Saul臈tekio, LT-10257 Vilnius
Tel. 239 8205
E-mail:

Head - Prof. Dr.. Lilija Kal臈dien臈

STAFF

Professors: Dr. L. Kal臈dien臈, Dr. N. Kuisien臈, Dr. A. Me拧kauskas, Dr. I. Girkontait臈.
Associate professors: Dr. E. Lastauskien臈, Dr. V. Ka拧臈ta.
Assistants: Dr. A. Gegeckas, Dr. R.Gudiukait臈.
Lecturers: Dr. J. Raugalas, R. Puzirauskas, Dr.. R. Kananavi膷i奴t臈, R. Petkauskait臈, A. Gricajeva, I. Burneikien臈. J. Lebedeva, J. Jurgelevi膷i奴t臈, Dr.. R.Ra啪anskas (part-time).
Researcher: Dr. A. Kaunietis.
Specialists: J. Lekavi膷i奴t臈, R.Jurkevi膷ien臈.
Doctoral students: A. Gricajeva, I. Burneikien臈, T. Kazanova, R. Bikmurzinas, J. Lebedeva, T. Kirtiklien臈, J. Jurgelevi膷i奴t臈.

RESEARCH INTERESTS

Genomics and biotechnologies: fundamental and applied microbial research
Research of microorganisms for innovative biotechnologies
Biocatalysts selection for biomass conversion
Prokaryotes for biotechnology, biopharmacy efficiency and safety food production development
Strategies in the antimicrobial therapy
Protein engineering

MAIN RESEARCH AREAS

Molecular taxonomy of prokaryotes
Microbial culture collections
Bioactive compounds of microorganisms
Bacterial collagen-like proteins
Electroporation and magnetoporation methods for the biocontrol of the skin colonizing microorganisms
Yeast prions
Microbial enzymes
Microbial biotechnologies
Bioremediation, biodegradation
Waste treatment

RESEARCH PROJECTS CARRIED OUT IN 2018

Projects Supported by University Budget

Selection of Micro-Organisms and Researches for Innovative Biotechnology Creation. Prof. Dr. L. Kal臈dien臈. 2018.

Work objective: Selection of microorganisms in order to create an effective biocatalyst for the development of biotechnology in the environment. Nowadays, for the industrial implementations, especially in the area of organic synthesis, immobilized enzymes are preferred over their soluble forms. The study aimed to find fast, cost-efficient, and effective way of lipase immobilization for the use in organic media. Lipases were immobilized utilizing cross-linking of enzyme aggregates, covalent immobilization on magnetite particles and adsorption-immobilization using pyrolyzed sugar industry waste product as a novel type of carrier. Enzyme immobilized on the sugar industry waste pyrolysis product was determined as a best way to hyperactivate. The use of the sugar industry waste pyrolysis product as a carrier provides a novel, cheap, fast, cost-efficient and eco-friendly way of immobilization with some crucial points to be noted for the best productivity.

Main publication:

Gricajeva, A., Kazlauskas, S., Kal臈dien臈, L. Bendikien臈 V. 2018. Analysis of Aspergillus sp. lipase immobilization for the application inorganic synthesis. Internatiol Journal of Biological Macromolecules,

Molecular Microbiology of Prokaryotes for Modern Biotechnology and Biopharmacy. Prof. Dr. N. Kuisien臈. 2018.

Work objective: the development of the new products for biotechnology and biopharmacy using modern methods of molecular microbiology of prokaryotes. Molecular approach was used to study epidemiology of Gram-negative pathogenic bacteria in Lithuanian hospitals. Our study revealed intensive inter- and intrahospital spread of these pathogenic bacteria usually carrying 1-7 genes conferring 尾-lactam resistance. In order to contribute to the development of novel antimicrobial compounds against these drug-resistant bacteria, screening for polyketide synthases and nonribosomal peptide synthetases genes was carried out in bacterial strains isolated from Krubera-Voronja Cave. Mining for bacteriocins, polyketide synthases, and nonribosomal peptide synthetases in the genomes of both thermophilic (Geobacillus) and mesophilic (Paenibacillus) endospore forming bacteria was also performed.

Main publication:

Kirtikliene, T., Naugzemys, D., Steponkiene, A., Bogdevic, R., Vizuje, G., Zvingila, D., Kusiene, N. 2018. Evaluation of the inter- and intrahospital spread of multidrug resistant Gram-negative bacteria in Lithuanian hospitals. Microb. Drug Resist., doi:

Determination of the Microorganisms Synthesized Antimicrobial Compounds, Protein Engineering and Application In Biotechnology. Dr. E. Lastauskien臈. 2018.

Work objective: Screening compounds exhibiting antibacterial and antifungal activity. Determination of the mechanisms of the action of the new antimicrobial compounds and analysis of the cell death type. Construction of the novel proteins with the potential application in biotechnology and biopharmacy.
In 2018, the new microbial producents synthesizing active compounds against pathogenic Candida yeasts and Fusarium spp. were discovered as well as the active compounds against pathogenic Pseudomonas, Staphylococcus, Streptococcus strains. By using direct evolution strategies, we improved microbial lipolytic enzyme and constructed the new fused lipolytic protein and analysed his application in the ester synthesis. Lipases as biocatalysts can be used in organic synthesis reactions to produce precursors of drug and bioactive compounds against microorganisms related to skin infections.

Main publication:

Malunavicius, V., Druteika, G., Sadauskas, M., Veteikyte, A., Matijosyte, I., Lastauskiene, E., Gegeckas, A., Gudiukaite, R. 2018. Usage of GD-95and GD-66 lipases as fusion partners leading to improved chimeric enzyme LipGD95-GD66. International Journal of Biological Macromolecules, vol. 118, p. 1594鈥�1603.

National Research Projects

Research Council of Lithuania Towards the Future Technologies Program project: Electro-magnetoporation Mediated Biocontrol of the Microgravity Affected and Skin Infections Causative Microorganisms ELMIGRAV (No. LAT-02/2016). Leader of VU part of the project PhD Egl臈 Lastauskien臈. Project leader: Jurij Novickij. 2016鈥�2018.

Main publications:

Lastauskiene, E., Novickij, V., Zinkevi膷iene, A., Girkontaite, I., Pa拧kevi膷ius, A., Svediene, J., Markovskaja, S., Novickij, J. 2018.Application of pulsed electric fields for the elimination of highly drug-resistant Candida grown under modelled microgravity conditions. Int Jour Astrobiol, doi: 10.1017/S1473550418000332.

Novickij, V., Svediene, J., Pa拧kevi膷ius, A., Markovskaja, S., Lastauskiene, A., Zinkevi膷iene, A., Girkontaite, I., Novickij, V. 2018. Induction of different sensitization patterns of MRSA to antibiotics using electroporation. Molecules, vol. 2018(23), 1799.

Novickij, V., Zinkevi膷ien臈, A., Valiulis, J., 艩vedien臈, J., Pa拧kevi膷ius, A., Lastauskien臈, E., Markovskaja, S., Novickij, J. 2018. Different permeabilization patterns of splenocytes and thymocytes to combination of pulsed electric and magnetic field treatments. Bioelectrochem., vol. 122, p. 183鈥�190.

Novickij, V., Zinkeviciene, A., Perminaite, E., Cesna, R., Lastauskiene, E., Paskevicius, A., Svediene, J., Markovskaja, S., Novickij, J., Girkontaite, I. 2018. Non-invasive nanosecond electroporation for biocontrol of surface infections: an in vivo study. Scientific Reports, vol. 8, No. 14516.

Research Council of Lithuania. Discovery of Novel Bioactive Microbial Compounds in the Unique Environment: an Investigation of the Diversity, Prevalence and Expression (No. S-MIP-17-21). Project leader: Dr. N. Kuisien臈. 2017鈥�2020.

Contractual Research

Cultivation of Haematococcus Pluvialis and the Optimization of Dry Biomass Release. CJSC FORTUM Klaip臈da. Project leader: Dr. L. Kal臈dien臈. 2017鈥�2018.

Creating a Method for Purification of Lactic Acid Bacteria and Maintaining Viability in a Special Medium. CLSC 沤emaitijos pienas. Project leader: Dr.L.Kal臈dien臈. 2018.

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

Nature Research Centre (Lithuania)
Vilnius Gediminas Technical University (Lithuania)
State Research Institute Centre for Innovative Medicine (Lithuania)
Centre for Physical Sciences and Technology (Lithuania)
The National Public Health Laboratory (Lithuania)
Thompson Rivers University (Canada)
Latvias University (Latvia)
University of Milan (Italy)
University of Ljubljana (Slovenia)

OTHER SCIENTIFIC ACTIVITIES

Prof. Dr. . L. Kal臈dien臈 鈥�

• president of Lithuanian Microbiological Society;
• member of Lithuania鈥檚 Genetically Modified Organisms Experts Committee.

Prof. PhD. N. Kuisien臈 鈥�

• vice president of Lithuanian Microbiological Society.

Assoc. Prof. Dr. E. Lastauskien臈 鈥�

• financier of Lithuanian Microbiological Society.

Asisst. Dr. A. Gegeckas 鈥�

• member of the board of Lithuanian Microbiological Society.

 

DEPARTMENT OF NEUROBIOLOGY AND BIOPHYSICS

7 Saul臈tekio, LT-10257 Vilnius
Tel. 239 8222
E-mail:

Head - Prof. Dr. Osvaldas Ruk拧臈nas

STAFF

Professors: Dr. A. Alaburda, Dr. D. Matulis (part-time), Dr. O. Ruk拧臈nas, Dr. V. Vengelien臈 (part-time), Dr. I. Gri拧kova-Bulanova.
Associate professors: Dr. V. Bukelskien臈 (part-time), Dr. R. Grik拧ien臈, Dr. V. Kisnierien臈, Dr. V. Sakalauskas, Dr. G. Svirskis (part-time), Dr. M. Korostenskaja (part-time).
Lecturers: Dr. R. Bui拧as, A. Daktari奴nas, R. Grigonis.
Senior research fellow: Dr. V. Sakalauskas.
Research fellow: Dr. V. Kisnierien臈.
Junior research fellows: A. Daktari奴nas, A. Voicikas.
Doctoral students: D. Dankin, A. 艩l臈ktait臈, L. Ma啪rimait臈, V. Mork奴nait臈, R. Grigonis, E. Jan臈nait臈, M. Baranauskas, D. Le拧膷i奴t臈-Krilavi膷ien臈, I. Lapeikait臈, A. Kalnaityt臈, A. Voicik, S. M臈lynyt臈, R. Mon膷iunskait臈, T. Paulauskas, E. Pipinis, V. Par膷iauskait臈, R. Dulinskas, S. Venclov臈, V. Survilien臈, T. Paulauskas, V. Par膷iauskait臈, A. Grabauskait臈, D. Dapkut臈.

RESEARCH INTERESTS

Functional organization and realization of information coding/processing and decision making in human and animal nervous system

RESEARCH PROJECTS CARRIED OUT IN 2018

Projects Supported by University Budget

Theoretical, Electrophysiological and Psychophysical Investigation of Information Coding and Processing. Prof. O. Ruk拧臈nas. 2016鈥�2020.

Mental rotation performance was compared between women using anti-androgenic oral contraceptives, naturally cycling women and men. Study results revealed lower performance accuracy of OC users which could be related to a less efficient performance strategy and naturally cycling women compared to oral contraceptive users demonstrate significantly higher general brain activity.
The psychophysical investigation of categorization of visual objects in the task of visual search and the mathematical modelling revealed that the categorization of simultaneously presented multiple objects are best characterized by the so called facilitated-successive strategy: the objects are categorized successively but the objects of the same category are categorized faster than the objects of different categories.
Inhibition/excitation balance was assessed in subjects with different Internet use habits. The results indicated that Internet Addiction Test score was positively correlated with alpha power obtained during eyes closed but not during eyes open. This was further supported by a negative correlation between Internet Addiction Test scores and alpha desynchronization. The current findings suggest that there are associations between neural activity and the vulnerability of problematic Internet use.
There was a strong negative correlation between firing frequency and threshold potential when spikes were induced by intracellulary-injected current. Contrary, there was no correlation between firing frequency and threshold potential during episodes of fictive scratch.
30 min. exposure to AP-5 hyperpolarizes excitation threshold potential of electrically evoked action potentials, and increases its amplitude in single Nitellopsis obtusa cell.

International Research Projects

Eat Me Microglia: Lipid Scrambling as a Signal for Synaptic Pruning, H2020: Marie Sklodovska Curie. Dr. U. Neni拧kyt臈. 2016鈥�2018.

IBRO Return Home Fellowship. Dr. U. Neni拧kyt臈. 2017鈥�2019.

Elektrini懦 signal懦 perdavimo ilgais atstumais sistemos adaptacija augalams persikeliant i拧 vandens 寞 sausum膮 (System Adaptation of Transmitting Electrical Signals Long Distances Moving Plants from Water to Dry Medium). Tarpvalstybin臈s programos (dvi拧al臈s, tri拧al臈s): Lietuvos - Lenkijos mokslo projektai. Dr. V. Kisnierien臈. 2018鈥�2021.

New EEG Clustering Methods for Pre-clinical and Clinical Applications, funded by Chilean funding agency Comisi贸n Nacional de Investigaci贸n Cient铆fica y Tecnol贸gica (CONICYT) in collaboration to Valparaiso University. Dr. I. Gri拧kova-Bulanova. 2018鈥�2019.

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

Republican Vilnius Psychiatric Hospital (Lithuania)
University of Copenhagen (Denmark)
Florida Children Hospital (USA)
University of Lausanne (Switzerland)
University of Poznan (Poland)
Kiev National Taras Shevchenko University (Ukraine)
Jagielonian University (Poland)
Auckland University of Technology (New Zealand)
Valparaiso University (Chile)
National Institute of Mental Health (Czech Republic)
Centre for Information and Neural Networks (Japan)

OTHER SCIENTIFIC ACTIVITIES

Prof. A. Alaburda 鈥�

• board member of the Lithuanian Society for Neurosciences;
• European Commission expert.

Dr. R. Bui拧as 鈥�

• member of the Lithuanian Society for Neurosciences.

Assoc. Prof. I. Gri拧kova-Bulanova 鈥�

• board member of the Lithuanian Society for Neurosciences;
• board member of International Brain Research Organization (IBRO);
• member of DANA Alliance for Brain Initiatives
• member of the European Dana Alliance for the Brain.

Assoc. Prof. R. Grik拧ien臈 鈥�

• secretary of the Lithuanian Society for Neurosciences.

Assoc. Prof. V. Kisnierien臈 鈥�

• board member of the Lithuanian Society for Neurosciences.

Dr. A. Pleska膷iauskas 鈥�

• member of the Lithuanian Society for Neurosciences.

Prof. O. Ruk拧臈nas 鈥�

• President of the Lithuanian Society for Neurosciences;
• board member of the Baltic Laboratory Animal Science Association (Balt-LASA);
• vice-president of the Lithuanian Laboratory Animal Science Association (Lith-LASA);
• editorial board member of the journal Laboratorin臈 medicina (Laboratory Medicine);
• European Commission expert;
• member of Federation of European Neuroscience Societies (FENS) governing board.

Dr. A. 艩oli奴nas 鈥�

• member of the Lithuanian Society for Neurosciences.
  鈥�

DEPARTMENT OF ZOOLOGY

7 Saul臈tekio, LT-10257 Vilnius
Tel. 239 8264
E-mail: .

Head 鈥� Prof. Habil. Dr. Rimantas Rakauskas

STAFF

Professors: Dr. S. Pod臈nas, Habil. Dr. R. Rakauskas, Dr. K. Arba膷iauskas (part-time).
Asociate professors: Dr. E. Budrys (part-time), Dr. E. Bukelskis, Dr. J. Tur膷inavi膷ien臈, Dr. V. Pod臈nien臈, Dr. R. Bernotien臈 (part-time), Dr. V. Rakauskas (part-time), Dr. A. Kaupinis (part-time), Dr. A. Petra拧i奴nas, Dr. A. Kri啪anauskien臈 (part-time).
Assistant professor: Dr. G. Skujien臈.
Lecturers: Dr. M. Biteniekyt臈, Dr. R. Auk拧tikalnien臈, S. Skuja.
Senior researcher: Dr. J. Havelka.
Doctoral students: J. Danilov, M. Adomaitis, A. Kamarauskait臈, I. Gorban.

RESEARCH INTERESTS

Ecosystems and global change
Mapping and catalogization of fauna
Rare and endangered species both in terrestrial and limnic systems
Biosystematic studies in insects (Hemiptera, Sternorrhycha: Aphididae and Diptera: Tipulomorpha), snails and slugs (Mollusca: Gastropoda), spiders (Araneae)

RESEARCH PROJECTS CARRIED OUT IN 2017

Projects Supported by University Budget

Animal Biodiversity, Ecology and Population Structure. Prof. Habil. Dr. R. Rakauskas. 2018鈥�2022.

Impact of the invasive New Zealand mud snail (Potamopyrgus antipodarum) to local littoral macroinvertebrate community evaluated. Capability of the red-tailed bumblebee (Bombus lapidarius L.) to self-establish in urban environment studied. Life cycle of Lithuanian populations of Cinara (Cinara) piniphila (Hemiptera, Aphididae) studied including the description of amphigonic morphs. Analysis of the biodiversity of spiders and dipterous insects of Lithuania continued. Hybridization analysis between the invasive slug species Arion lusitanicus and local Arion species (Gastropoda, Arionidae) performed. Distribution analysis of Unio crassus (Bivalvia, Unionidae) in Lithuania performed. Monitoring of fish communities in Lithuanian lakes was continued. Monitoring of black storks, birds of prey and owls in forests of eastern and southern Lithuania continued. A preliminary review of winter gnat (Diptera, Trichoceridae) fauna of Bulgaria, Romania and Serbia was finalized, one species new to science described. Taxonomic studies of the Korean libnotes crane flies (Diptera: Limoniidae) performed.

Main publications:

Theodorou, P., Radzeviciute, R., Kahnt, B. et al. 2018. Genome-wide single nucleotide polymorphism scan suggests adaptation to urbanization in an important pollinator, the red-tailed bumblebee (Bombus lapidarius L.). Proceedings of the Royal Society B-Biological Sciences, vol. 285(1877), doi: 10.1098/rspb.2017.2806 IF 4.847.

Rakauskas, V., Sidagyte, E., Butkus, R. et al. 2018. Effect of the invasive New Zealand mud snail (Potamopyrgus antipodarum) on the littoral macroinvertebrate community in a temperate mesotrophic lake. Marine and Freshwater Research, vol. 69(1), p. 155鈥�166, doi: 10.1071/MF17059 IF 1.674.

Podenas, S., Byun, H-W. 2018. Libnotes crane flies (Diptera: Limoniidae) from Jeju Island (South Korea). ZOOTAXA, vol. 4483(2), p. 375鈥�384, doi: 10.11646/zootaxa.4483.2.9 IF 0.931.

National Research Projects

Research Council of Lithuania. Biodiversity and Ecological Peculiarities of Aphid Species (Hemiptera: Adelgidae, Lachnidae) Inhabiting Coniferous Host Plants In Central Europe (No. P-MIP-17-365). Prof. R. Rakauskas. 2017鈥�2020.

Research Council of Lithuania. International Cooperation Enhancement and Qualification Internship at the University of Drexel Natural Sciences Academy (USA) (No. 09.3.3-LMT-K-712). Prof. S. Pod臈nas. 2018.

Project supported by Ministry of Agriculture 鈥� The Role of Insects in Dissemination of African Swine Fever Virus (No MT-18-4). Assoc. Prof. J. Tur膷inavi膷ien臈. 2018.

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

Institute of Ecology, Nature Research Centre (Lithuania)
Kaunas Tadas Ivanauskas Museum of Zoology (Lithuania)
Silesian University, Katowice (Poland)
Institute of Entomology, Czech Academy of Sciences (Czech Republic)
Institute of Zoology, Saint Petersburg (Russia)

OTHER SCIENTIFIC ACTIVITIES

Assoc. Prof. E. Bukelskis 鈥�

• member of the Council of the Lithuanian Hydrobiological Society;
• member of the National Council for the Fishing Management.

Prof. S. Pod臈nas 鈥�

• assoc. researcher of the Academy of Natural Sciences, Philadelphia, PA (USA);
• expert of the National Centre for Quality Assessment in Higher Education (Lithuania);
• Head of the Laboratory of Entomology, Institute of Ecology, Nature Research Centre (Lithuania).

Prof. R. Rakauskas 鈥�

• expert of the National Centre for Quality Assessment in Higher Education;
• expert of the Research Council of Lithuania;
• member of the Lithuanian Entomological Society;
• member of the Scientific Committee of the 8th European Hemiptera Congress; ().

Assoc. Prof. J. Tur膷inavi膷ien臈 鈥�

• expert of Supervision Committee of Genetically Modified Organisms;
• editorial board member of the journal Bulletin of the Lithuanian Entomological Society;
• member of the Lithuanian Entomological Society.

Lect. Dr. R. Auk拧tikalnien臈 鈥�

• member of the Lithuanian Morphological Society.

Assist. Prof. G. Skujien臈 鈥�

• curator of the Museum of Zoology of 91桃色;
• member of the Lithuanian Entomological Society;
• external expert of Molluscs of the Commission of the Lithuanian Language;
• member of the Council of the Invasive Species of Lithuania;
• member of ETHOS, Lithuanian Ethical Culture Society;
• member of Bioethics Society;
• member of Family Planning and Sexual Health Association.

Assoc. Prof. A. Petra拧i奴nas 鈥�

• member of the Commission of the Lithuanian Red Data Book;
• president of the Lithuanian Entomological Society;
• managing editor of the journal Bulletin of the Lithuanian Entomological Society;
• member of EAFE, European Association for Forensic Entomology.

Lect. Dr. M. Biteniekyt臈 鈥�

• member of the Lithuanian Entomological Society.

Lect. S. Skuja 鈥�

• member of the Lithuanian Ornithological Society;
• member of the Lithuanian Entomological Society.
  鈥�

CENTRE FOR ECOLOGY AND ENVIROMENTAL RESEARCH

7 Saul臈tekio, LT-10257 Vilnius
Tel. 239 8299
E-mail:

Head 鈥� Prof. Dr. Alius Ulevi膷ius

STAFF

Professor: Dr. A. Ulevi膷ius.
Associate professors: Dr. G. Ignatavi膷ius, Dr. J. Satk奴nas (part-time), Dr. V. O拧kinis.
Assistants: Dr. V. Kalcien臈, Dr. I. Nedveckyt臈, Dr. A. Samas, Dr. V. Valskys.
Lecturer: G.Trakimas.

RESEARCH INTERESTS

Pollution of natural components and anthropogenic environmental impact assessment
Toxic impacts of environmental pollutants to ecosystems using tests of luminescent microorganisms and biomarkers
Impacts of key stone species to structure and functioning of ecosystems using GIS, camera traps and stable isotopes
Infochemical interactions and behaviour of organisms

RESEARCH PROJECTS CARRIED OUT IN 2018

Projects Supported by University Budget

Pollution of Bottom Sediments by Heavy Metals in Water Bodies and Sapropel Quality Was Assessed in Lakes of Lithuania. Prof. Dr. A. Ulevi膷ius, Assoc. Prof. Dr. G. Ignatavi膷ius. 2018.

Vehicle-animal collisions and their natural and anthropogenic factors.
Ecotoxicity estimation of surface water sewage with standard bioassay test-Aliivibrio fischeri and luminescent Escherichia coli.
Geomorphological and biocenotical impacts of Eurasian beaver Castor fiber.
Chemoreception of phytophagous insects and plant allelopathy.

Main publications:

Ignatavicius, G., Valskys, V. 2018. The influence of time factors on the dynamics of roe deer collisions with vehicles. Landscape and Ecological Engineering, vol. 14(2), p. 221鈥�229.

Krams, I., Trakimas, G., Kecko, S., Elferts, D., Krams, R., Luoto, S., Rantala, M.J, M盲nd, M., Kuusik, A., Kek盲l盲inen, J., J玫ers, P., Kortet, R., Krama, T. 2018. Linking organismal growth, coping styles, stress reactivity, and metabolism via responses against a selective serotonin reuptake inhibitor in an insect. Scientific Reports, vol. 8: 8599.

National Research Projects

Research Council of Lithuania. Assessment of Cumulative Toxicity Impact in the Aquatic Organisms Induced by Different Types of Stressors, ACTIS. Dr. V. Kalcien臈. 2017鈥�2020.

International Research Projects

INTERREG Baltic Sea Region Project. Water Management in Baltic Forests (WAMBAF). Dr. A. Ulevi膷ius. 2016鈥�2018.

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

Nature Research Centre (Lithuania)
Centre for Physical Sciences and Technology (Lithuania)
Vilnius Gediminas Technical University (Lithuania)
University of Latvia (Latvia)
Lithuanian Geological Survey (Lithuania)

OTHER SCIENTIFIC ACTIVITIES

Dr. V. Kalcien臈 鈥�

• associate member of Royal Society of Chemistry;
• member of Society of Environmental Toxicology and Chemistry;
• member of Lithuanian Biochemical Society.