V. Simanavičienė. Molecular diagnostics of human papillomavirus (HPV) and studies on HPV prevalence.
E. Jakubauskienė. Pre-mRNA splicing: regulation of monoamine ozidase B and oxygen-dependent genes expression.
P.L. Tamošiūnas. Yeast-generated parvoviral virus-like particles and their use in diagnostics.
K. Olechnovič. Methods for the analysis and assessment of the three-dimensional structures of proteins and nucleic acids: development and applications.
G. Kostiuk. Single molecule studies of the monomeric restriction endonuclease BcnI-DNA interactions.
V. Raškevičius. Computational studies of protein and ligand interactions.
V. Linkuvienė. Observed and intrinsic thermodynamic and kinetic parameters of sulfonamide derivative binding to carbonic anhydrases.

MAIN SCIENTIFIC ACHIEVEMENTS IN 2017

A research team at the Institute of Biotechnology has discorvered a new signalling pathway related to the CRISPR phenomenon leading to a publication in the journal Science (Kazlauskienė M., Kostiuk G., Venclovas Č., Tamulaitis G., Šikšnys V. A cyclic oligonucleotide signaling pathway in type III CRISPR-Cas systems. 2017, doi: 10.1126/science.aao0100).

The complete genomic sequence of a patogenic bacterium, Gardinella vaginalis, has been determined by scientists of the Institute, which contributed to unveiling new disease mechanisms (Janulaitienė M., Paliulytė V., Grincevičienė Š., Zakarevičienė J., Vladisauskienė A., Marcinkutė A., Plečkaitytė M. Prevalence and distribution of Gardnerella vaginalis subgroups in women with and without bacterial vaginosis. BMC Infect. Dis. 2017, 17:394. DOI 10.1186/s12879-017-2501-y).

DEPARTMENT OF PROTEIN - DNA INTERACTIONS

7 Saulėtekio av., LT-10257 Vilnius

Tel. 223 4354, fax 223 4367

E-mail:

Head - Prof. Dr. Virginijus Šikšnys

STAFF

Chief research fellows: Prof. Dr. V. Šikšnys, Dr. S. Gražulis, Dr. G. Sasnauskas, Dr. M. Zaremba.
Senior research fellows: Dr. G. Tamulaitienė, Dr. E. Manakova, Dr. G. Tamulaitis, Dr. G. Gasiūnas.
Research fellows: Dr. A. Šilanskas, Dr. T. Šinkūnas, Dr. T. Karvelis.
Junior research fellows: Dr. G. Kostiuk, P. Toliušis, I. Songailienė, E. Stankė, A. Merkys.
Doctoral students: M. Kazlauskienė, A. Vaitkus, G. Drabavičius, A. Grybauskas, G. Bigelytė, E. Golovinas.

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.

RESEARCH PROJECTS CARRIED OUT IN 2017

Projects Supported by University Budget

Structure-Function Relationship of Proteins and Protein Complexes. Prof. Dr. V. Šikšnys. 2016–2018.

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.

Main publications:

Tamulaitiene G, Jovaisaite V, Tamulaitis G, Songailiene I, Manakova E, Zaremba M, Grazulis S, Xu SY, Siksnys V. 2017. Restriction endonuclease AgeI is a monomer which dimerizes to cleave DNA. Nucleic Acids Res., vol. 45(6), p. 3547–3558; doi: 10.1093/nar/gkw1310.

Sasnauskas G, Tamulaitiene G, Tamulaitis G, Calyševa J, Laime M, Rimšeliene R, Lubys A, Siksnys V. 2017. UbaLAI is a monomeric Type IIE restriction enzyme. Nucleic Acids Res., vol. 45(16), p. 9583–9594; doi: 10.1093/nar/gkx634.

National Research Projects

Research Council of Lithuania. Single Molecule and Structural Studies of a New Type of Restriction Endonucleases (No. MIP 56/2015). Dr. M. Zaremba. 2015–2017.

The objects of research of this project CglI and NgoAVII belong to a new type of restriction endonucleases that according to their genetic organization, composition of protein complex and mode of action differ from other types of restriction endonucleases. CglI and NgoAVII are composed of two proteins: an R-protein, which is responsible for DNA target recognition and cleavage, and an N-protein, possessing an ATPase activity. It was demonstrated that in the case of the CglI system the R- and N-proteins assemble into a functional heterotetrameric protein complex with a R2N2 stoichiometry. Both catalytically active proteins and extensive ATP hydrolysis are required for specific DNA cleavage near the recognition sequence. Therefore, the restriction endonucleases CglI and NgoAVII employ a unique not yet elucidated catalytic mechanism for DNA cleavage. Elucidation of the structural mechanism of the new type ATP-dependent restriction endonucleases is the major focus of this research project. The following questions will be addressed: what conformational changes occur in the proteins upon specific DNA target recognition; how is an ATPase activated; whether and how do proteins translocate on DNA; how is a double-stranded DNA break introduced; what is the structure of the functional RN-complex.

Main publications:

Toliusis P, Zaremba M, Silanskas A, Szczelkun MD, Siksnys V. 2017. CgII cleaves DNA using a mechanism distinct from other ATP-dependent restriction endonucleases. Nucleic Acids Res., vol. 45(14), p. 8435–8447; doi: 10.1093/nar/gkx580.

Research Council of Lithuania. Structure‐Function Relationship of the B3 DNA Binding Domains (No. MIP 106/2015). Dr. G. Sasnauskas. 2015–2018.

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. Csm Effector Complex Labelling for Single Molecule FRET Experiments (No. APP-03/2016). Dr. G. Tamulaitis. 2016–2018.

Recently we have shown 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.

Main publications:

Kazlauskiene M, Kostiuk G, Venclovas Č, Tamulaitis G, Siksnys V. 2017. A cyclic oligonucleotide signaling pathway in type III CRISPR-Cas systems. Science, vol. 357(6351), p. 605–609; https://doi.org/10.1126/science.aao0100

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

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 a 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. 2017–2020.

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. “DNA curtains” is the next step in the development of the high-throughput SM methods. “DNA curtains” 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 our developed platform to be relevant and broadly applied in other research groups in the near future 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. 2017–2020.

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‐silencing 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’ 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. Gražulis. 2016–2020.

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 are 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. 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. Gasiūnas. 2017–2019.

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.

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

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

OTHER SCIENTIFIC ACTIVITIES

Prof. Dr. V. Šikšnys –

member of the Lithuanian Academy of Sciences;
member of EMBO.

DEPARTMENT OF BIOLOGICAL DNA MODIFICATION

7 Saulėtekio av., LT-10257 Vilnius

Tel. 223 4350, fax 223 4367

E-mail:

Head - Prof. Habil. Dr. Saulius Klimašauskas FRSC

STAFF

Chief research fellows: Prof. Habil. Dr. S. Klimašauskas, Dr. G. Vilkaitis, Dr. V. Masevičius.
Senior research fellows: Dr. E. Kriukienė, Dr. R. Rakauskaitė.
Research fellows: Dr. J. Gordevičius, Dr. M. Tomkuvienė, Dr. V. Stankevičius.
Junior research fellows: G. Urbanavičiūtė, A. Osipenko, Z. Staševskij, J. Ličytė, M. Mickutė.
Technical staff: A. Rukšėnaitė.
Doctoral students: S. Gasiulė, P. Gibas, M. Rudytė.

RESEARCH INTERESTS

Nucleic acids modification enzymes
Epigenome profiling
Biosynthesis of selenoproteins
Enzyme engineering

RESEARCH PROJECTS CARRIED OUT IN 2017

Projects Supported by University Budget

Nucleic Acids Modification Enzymes: Structure, Mechanisms of Action and Directed Engineering. Prof. Habil. Dr. S. Klimašauskas. 2016–2018.

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.

Main publications:

Staševskij, Z., Gibas, P., Gordevičius, J., Kriukienė, E., Klimašauskas, S. 2017. Tethered Oligonucleotide-Primed sequencing, TOP-seq: a high-resolution economical approach for DNA epigenome profiling. Molecular Cell, vol. 65(3), p. 554–564. e6; doi: 10.1016/j.molcel.2016.12.012.

Tomkuvienė, M., Ličytė, J., Olendraitė, I., Liutkevičiūtė, Z., Clouet-d’Orval, B., Klimašauskas, S. 2017. Archaeal fibrillarin-NOP5 heterodimer 2’-O-methylates RNA independently of the C/D guide RNP particle. RNA, vol. 23, p.1329–1337; doi: 10.1261/rna.059832.116.

Daniūnaitė, K., Dubikaitytė, M., Gibas, P., Bakavičius, A., Lazutka, J. R., Ulys, A., Jankevičius, F., Jarmalaitė, S. 2017. Hum. Mol. Genet., vol. 26(13), p. 2451–2461; doi: 10.1093/hmg/ddx138.

National Research Projects

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. 2015–2018.

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.

Main publication:

Osipenko, A., Plotnikova, A., Nainytė, M., Masevičius, V., Klimašauskas, S., Vilkaitis, G. 2017. Oligonucleotide-Addressed Covalent 3’-Terminal Derivatization of Small RNA Strands for Enrichment and Visualization. Angew. Chem. Int. Ed., vol. 56(23), p. 6507–6510; doi: 10.1002/anie.201701448.

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. 2016–2018.

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. Klimašauskas. 2017–2020.

Photochemical transformations enable exquisite spatio-temporal control over biochemical processes, however, methods for reliable site-selective modification of proteins with biocompatible photosensitive 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. Kriukienė. 2017–2020.

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 that 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. Klimašauskas. 2017–2022.

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 the 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.

Granted Patent:

Klimašauskas S., Staševskij, Z. Nucleic acid production and sequence analysis. EP2776575B1. Publication date: 22.03.2017

Patent Applications:

Klimašauskas S., Vilkaitis G., Mickutė M. Analysis of single-stranded RNA. US15/559689. Filing date: September 19, 2017.

Klimašauskas S., Vilkaitis G., Mickutė M. Analysis of single-stranded RNA. EP16720576.4. Filing date: October 19, 2017.

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)
Institute of Molecular Genetics, Moscow (Russia)
Hokkaido University, Sapporo (Japan)
University of Stavanger, Stavanger (Norway)

OTHER SCIENTIFIC ACTIVITIES

Prof. Habil. Dr. S. Klimašauskas –

member of the Lithuanian Academy of Sciences;
fellow of the Royal Society of Chemistry;
EMBO member;
editorial advisory board member of the Open Life Sciences, https://www.degruyter.com/view/j/biol;
management committee member, COST actions CM1303, CM1406.

DEPARTMENT OF EUKARYOTE GENETIC ENGINEERING

7 Saulėtekio av., LT-10257 Vilnius

Tel. 223 4421, fax 223 4367

E-mail:

Heads - Dr. Gintautas Žvirblis (until May 1^st)

Dr. Rasa Petraitytė-Burneikienė (since May 2^nd)

STAFF

Chief research fellows: Prof. Habil. Dr. K. Sasnauskas, Dr. A. Gedvilaitė.
Senior research fellows: Dr. R. Petraitytė-Burneikienė, Dr. A. Ražanskienė, Dr. R. Slibinskas, Dr. G. Žvirblis.
Research fellows: Dr. V. Kazanavičiūtė, Dr. R. Ražanskas, Dr. E. Čiplys, Dr. D. Žiogienė.
Junior research fellows: Dr. M. Zaveckas, Dr. A. Abraitienė, Dr. A. Bulavaitė, Dr. P. L. Tamošiūnas, M. Norkienė, J. Lazutka.
Other researchers: E. Rudokienė, R. Vorobjovienė, M. Valavičiūtė.
Doctoral students: E. Bakūnaitė, N. Macijauskaitė, G. Mickienė, M. Norkienė, U. Starkevič, R. Vorobjovienė, R. Zinkevičiūtė, Š. Paškevičius, Ž. Dapkūnas, J. Nainys, E. Žitkus, A. Špakova, M. Valavičiūtė.

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

RESEARCH PROJECTS CARRIED OUT IN 2017

National Research Projects

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

Recently it has been shown that the majority of eukaryotic gene has a surprisingly large variety of protein translation start point in noncoding 5’-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’-end of mRNA. The project goal is to create immunochemical, antibody-based methods allowing testing 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. Gedvilaitė. 2017–2020.

Yeast, especially Saccharomyces cerevisiae, serve 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’s 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. Petraitytė-Burneikienė. 2017–2019.

Meningitis, encephalopathy and encephalitis are serious diseases of the central nervous system that are often 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. Žvirblis, Dr. R.Petraitytė-Burneikienė.

Recombinant Viral Proteins. Euroimmun AG, Germany. Dr. A. Ražanskienė.

Recombinant Viral Proteins. Arc Dia International Oy Ltd, Finland. Dr. R.Petraitytė-Burneikienė.

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 für Tiergesundheit, Federal Research Institute for Animal Health OIE Collaborating Centre for Zoonoses in Europe (Germany)
Max Planck Institute for Molecular Plant Physiology (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)

SECTOR OF MICROTECHNOLOGIES

7 Saulėtekio av., LT-10257 Vilnius

Tel. 223 4356, fax 223 4367

E-mail:

Head - Dr. Linas Mažutis

STAFF

Chief research fellow: Prof. A. Janulaitis.
Senior research fellow: Dr. L. Mažutis.
Other researchers: D. Kučiauskas, K. Simutis, V. Milkus, G. Stonytė, J. Nainys, K. Leonavičius, K. Goda, L. Karpus, J. Ritmejeris.
Doctoral students: R. Galinis, J. Rutkauskaitė, V. Kiseliovas, V. Milkus, R. Žilionis, J. Nainys, G. Stonytė.

RESEARCH INTERESTS

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

RESEARCH PROJECTS CARRIED OUT IN 2017

International Research Projects

H2020 FRAMEWORK PROGRAMME: High Throughput Screening of Single-Cells Using Droplet Microfluidics – Cells-In-Drops (No. 705791). Dr. L. Mažutis. 2016–2018.

Analysis of single-cells is becoming increasingly important in different branches of biology and biomedicine. Many useful techniques have been developed to profile and even selectively purify single-cells, however, the demand for methods with better analytical performance and improved high-throughput capabilities, remains very high. Droplet microfluidics can fulfill this demand by bringing higher throughput, scalability and single molecule resolution. In this project, a droplet microfluidics platform we aim to develop a system for high-throughput single-cell screening and sequencing of immune cells, including primary B-cells that produce therapeutic antibodies or biomolecules of biomedical interest. We are using cell compartmentalization into microfluidic droplets together with capture beads and barcoded DNA primers that enable a direct establishment of the linkage between the genotype (genes or mRNA) and phenotype (binding, regulatory or activity of secreted proteins). Like no other system available to-date this technological approach should provide a unique way to identify the primary sequence of heavy and light IgG genes encoding functional monoclonal antibodies directly from single-cells, without a need to perform gene cloning or cell immortalization. The results of this work are likely to bring a significant impact not only in applied biological sciences but also in biotechnology and biomedicine.

Main publications:

Engblom, C., Pfirschke, C., Zilionis, R., Da Silva Martins, J., Bos, S. A., Courties, G., Rickelt, S., Severe, N., Baryawno, N., Faget, J., Savova, V., Zemmour, D., Kline, J., Siwicki, M., Garris, C., Pucci, F., Liao, H. W., Lin, Y. J., Newton, A., Yaghi, O. K., Iwamoto, Y., Tricot, B., Wojtkiewicz, G. R., Nahrendorf, M., Cortez-Retamozo, V., Meylan, E., Hynes, R. O., Demay, M., Klein, A., Bredella, M. A., Scadden, D. T., Weissleder, R., Pittet, M. J. 2017. Osteoblasts remotely supply lung tumors with cancer-promoting SiglecF(high) neutrophils. Science, 358(6367); doi: 10.1126/science.aal5081.

Kiseliovas, V., Milosevic, M., Kojic, M., Mazutis, L., Kai, M., Liu,Y.T., Yokoi, K., Ferrari, M., Ziemys, A. 2017. Tumor progression effects on drug vector access to tumor-associated capillary bed. J Control Release, 2017 May 30. pii: S0168-3659(17)30626-0.

Zubaite, G., Simutis, K., Galinis, R., Milkus, V., Kiseliovas, V., Mazutis, L. 2017. Droplet microfluidics approach for single-DNA molecule amplification and condensation into DNA-magnesium-pyrophosphate particles. Micromachines, vol. 8, p. 62.

Zilionis, R., Nainys, J, Veres, A., Savova, V., Zemmour, D., Klein, MA., and Mazutis, L. 2017 Single-cell barcoding and sequencing using droplet microfluidics. Nature Protocols, vol. 12, p. 44–73.

Contractual Research

Research project with undisclosed biotech company. The goal of this project is to establish a high-throughput droplet microfluidics approach for capture and sequencing antibody-encoding genes from single-cells.

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

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

OTHER SCIENTIFIC ACTIVITIES

Dr. L.Mažutis -

Participation in Human Cell Atlas project;
Start-up Droplet Genomics, Vilnius, LT;
Start-up Platelet Biogenesis Inc. Boston, MA, USA.

Awards:

2017 American-Lithuanian Innovation Award, First Place (USA);
2017 Global Lithuanian Leaders Award (Innovations);
2017 Vilnius University Rector Award.

DEPARTMENT OF IMMUNOLOGY AND CELL BIOLOGY

7 Saulėtekio av., LT-10257 Vilnius

Tel. 223 4360, fax 223 4367

E-mail:

Head - Dr. Aurelija Žvirblienė

STAFF

Chief research fellow: Dr. A. Žvirblienė.
Senior research fellows: Dr. I. Kučinskaitė-Kodzė, Dr. M. Plečkaitytė, Dr. J. Matulienė, Dr. A. Kanopka.
Research fellows: Dr. P. Stakėnas, Dr. E. Jakubauskienė.
Junior research fellows: I. Dalgėdienė, R. Lasickienė, I. Pečiulienė, Dr. V. Simanavičienė, A. Vaitiekaitė, M. Janulaitienė.
Other researchers: D. Stravinskienė, D. Bakonytė.
Doctoral students: D. Stravinskienė, L. Vilys, M. Janulaitienė, M. Zilnytė, V. Rubinaitė, A. Lučiūnaitė, M. Simanavičius.

RESEARCH INTERESTS

Monoclonal and recombinant antibodies
Molecular epidemiology of Mycobacterium tuberculosis
Alternative splicing

RESEARCH PROJECTS CARRIED OUT IN 2017

Projects Supported by University Budget

Development of Novel Antibodies and Testing of their Properties. Dr. A. Žvirblienė. 2016–2020.

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.

Main publications:

Bulavaitė, A., Lasickienė, R., Tamošiūnas, P.L., Simanavičius, M., Sasnauskas, K., Žvirblienė, A. 2017. Synthesis of human parainfluenza virus 4 nucleocapsid-like particles in yeast and their use for detection of virus-specific antibodies in human serum. Appl Microbiol Biotechnol, vol. 101(7), p. 2991–3004.

Rimseliene, R., Ulcinaite, D., Gagiliene, B., Sukackaite R., Zvirbliene A., Kucinskaite-Kodze, I., Dekaminaviciute, D. 2017. Antibodies that bind thermophillic DNA polymerases. PCT/EP2017/050648.

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. Kučinskaitė-Kodzė. 2015–2018.

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).

Main publication:

Simanavicius, M., Tamosiunas, P.L., Petraityte-Burneikiene, R., Johne, R., Ulrich, R.G., Zvirbliene, A., Kucinskaite-Kodze, I. 2017. Generation in yeast and antigenic characterization of hepatitis E virus capsid protein virus-like particles. Appl Microbiol Biotechnol.; doi: 10.1007/s00253-017-8622-9

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. Žvirblienė. 2015–2018.

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. Plečkaitytė. 2017–2020.

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.

Main publications:

Janulaitiene, M, Paliulyte, V, Grinceviciene, S, Zakareviciene, J, Vladisauskiene, A, Marcinkute, A, Pleckaityte, M. 2017. Prevalence and distribution of Gardnerella vaginalis subgroups in women with and without bacterial vaginosis. BMC Infect Dis, vol. 17 (1), p. 394.

Tankovic, J, Timinskas, A, Janulaitiene, M, Zilnyte, M, Baudel, JL, Maury, E, Zvirbliene, A, Pleckaityte, M. 2017. Gardnerella vaginalis bacteremia associated with severe acute encephalopathy in a young female patient. Anaerobe, vol. 47, p. 132–134.

Contractual Research

Characterization of Allergens and Development of Allergen-Specific Antibodies. UAB Imunodiagnostika, Vilnius.

Generation of Monoclonal Antibodies. Abcam Ltd, UK. Dr. A. Žvirblienė.

Generation of Monoclonal Antibodies. Santa Cruz Biotechnology Inc., US. Dr. A. Žvirblienė.

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 Saulėtekio av., LT-10257 Vilnius

Tel. 223 4364, fax 223 4367

E-mail:

Head - Dr. Daumantas Matulis

STAFF

Chief research fellow: Dr. D. Matulis.
Senior research fellows: Dr. A Zubrienė, Dr. V. Petrikaitė, Dr. V. Petrauskas, Dr. V. Smirnovas, Dr. J. Matulienė.
Research fellows: Dr. V. Dudutienė, Dr. L. Baranauskienė, Dr. E. Čapkauskaitė, Dr. E. Kazlauskas.
Junior research fellows: Dr. V. Juozapaitienė, V. Michailovienė, J. Jachno, V. Linkuvienė, A. Zakšauskas, Š. Grincevičienė.
Other researchers: Affiliated Prof. G. Dienys, T. Šneideris, A. Smirnov, A. Janonienė.
Doctoral students: R. Mališauskas, A. Smirnov, V. Linkuvienė, J. Kazokaitė, A. Janonienė, T. Šneideris, J. Smirnovienė, G. Skvarnavičius.

RESEARCH INTERESTS

We study the thermodynamics and kinetics of protein – small ligand binding and are interested in the fundamental understanding of the protein – 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.

RESEARCH PROJECTS CARRIED OUT IN 2017

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. Matulienė. 2015–2018.

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). 12 catalytically active carbonic anhydrase isoforms in the human body 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.

Main publication:

Zhang, H., Liu, D., Wang, L., Liu, Z., Wu, R., Janonienė, A., Ma, M., Pan, G., Baranauskienė, L., Zhang, L., Cui, W., Petrikaitė, V., Matulis, D., Zhao, H., Pan, J., Santos, H.A. 2017. Microfluidic encapsulation of prickly zinc-doped copper oxide nanoparticles with VD1142 modified spermine acetalated dextran for efficient cancer herapy. Advanced Healthcare Materials. 1601406; doi:10.1002/adhm.201601406.

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

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 – Target Interaction (No. TAP LLT-1/2016). Dr. D. Matulis. 2016–2018.

The three research teams of this proposal, Taiwanese, Latvian, and Lithuanian, have combined their efforts to improve the knowledge of protein – drug recognition and to make compounds that will 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.

Main publications:

Čapkauskaitė E., Linkuvienė V., Smirnov A., Milinavičiūtė G., Timm D.D., Kasiliauskaitė A., Manakova E., Gražulis S., Matulis D. 2017. Combinatorial design of isoform-selective N-alkylated benzimidazole-based inhibitors of carbonic anhydrases. Chemistryselect., vol. 2(19), p. 5360–5371; doi: 10.1002/slct.201700531.

Vaškevičienė I., Paketurytė V., Zubrienė A., Kantminienė K., Mickevičius V., Matulis D. 2017. N-Sulfamoylphenyl- and N-sulfamoylphenyl-N-thiazolyl-b-alanines and their derivatives as inhibitors of human carbonic anhydrases. Bioorg Chem., vol. 75, p. 16–29.

Zubrienė, A., Smirnov, A., Dudutienė, V., Timm, D. D., Matulienė, J., Michailovienė, V., Zakšauskas, A., Manakova, E., Gražulis, S., Matulis, D. 2017. Intrinsic thermodynamics and structures of 2,4- and 3,4-substituted fluorinated benzenesulfonamides binding to carbonic anhydrases. ChemMedChem., vol. 12, p. 161–176.

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

Prion-like spreading may be employed in a number of fatal neurodegenerative disorders, including such as Alzheimer’s and Parkinson’s 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 – 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)

OTHER SCIENTIFIC ACTIVITIES

Dr. D. Matulis –

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 (2014-present).

SECTOR OF APPLIED BIOCATALYSIS

7 Saulėtekio av., LT-10257 Vilnius

Tel. 223 4371, fax 223 4367

E-mail:

Head - Dr. Inga Matijošytė

STAFF

Research fellow: Dr. I. Matijošytė.
Junior research fellows: M. Šulcienė, R. Šiekštelė.
Other researchers: A. Veteikytė, A. Sirvydaitė, affiliated prof. G. Dienys.
Doctoral students: V. Matikevičienė, M. Šulcienė.

RESEARCH INTERESTS

Biocatalysts and their application

RESEARCH PROJECTS CARRIED OUT IN 2017

Projects Supported By University Budget

Development and Investigation of Novel Biocatalysts and their Respective Processes. Dr. I. Matijošytė. 2015–2017.

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 2017, research was focused on the development of screening systems for targeted enzyme activities, development of protein expression systems for production of targeted enzymes and exploring carrier-free immobilization methods.

Main publications and licenses:

Veteikytė, R. Šiekštelė, B. Tvaska, I. Matijošytė. 2017. Sequential application of waste whey as a medium component for Klyuveromyces lactis cultivation and a co-feeder for lipase immobilization by CLEA method. Applied Microbiology and Biotechnology, vol. 101, p. 3617–3626.

Systems for measuring activities of the enzymes used in the feed production. License agreement LCS-15600-1909 (6 November 2017), Dr. I. Matijošytė.

Contractual Research

The Search and Investigation of Novel Microorganisms with the Exposed Features for Biogeocenosis. JSC BioenergyLT, N° MTS-560000-835, Lithuania, Dr. I. Matijošytė.

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

Investigation of Biogeocenosis Features of Microorganism. JSC BioenergyLT, N° MTS-560000-895, Lithuania, Dr. I. Matijošytė.

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

Investigation the Hydrolysis of Milk Proteins. Innovation voucher with Pienas LT, N° TPS-600000-1386, Lithuania, Dr. I. Matijošytė.

The aim was to investigate enzymatic hydrolysis of some milk production fractions into valuable peptides.

Investigation of Milk Fractionation and its Structural Features. Pienas LT, N°MTS-560000-1624, Lithuania, Dr. I. Matijošytė.

The aim was to investigate and define optimal parameters for milk fractionation and to explore the structural properties of the obtained fractions.

Collaboration Contracts

Enzymes and their application in detergents. SC Naujoji Ringuva, N° B1-560000-153, I. Matijošytė, (open-ended).

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

University of Applied Sciences (Switzerland)
TU Delft (the Netherlands)
Leiden University (the Netherlands)
University of Seville (Spain)
University of Turin (Italy)

OTHER SCIENTIFIC ACTIVITIES

Dr. I. Matijošytė -

MC substitute member of COST Action 1303;
National representative in State Representative Group (SRG) at Bio-Based Industry Joint Undertaking;
member of working group Preparation of technical specification for the feasibility study on Bioeconomy development in Lithuania. N° 4-642 (Ministry of Economy).

DEPARTMENT OF BIOINFORMATICS

7 Saulėtekio av., LT-10257 Vilnius

Tel. 223 4368, fax 223 4367

E-mail:

Website: http://bioinformatics.lt

Head - Dr. Česlovas Venclovas

STAFF

Chief research fellow: Dr. Č. Venclovas.
Senior research fellow: Dr. V. Kairys.
Research fellows: Dr. M. Margelevičius, Dr. J. Dapkūnas, Dr. A. Timinskas, Dr. D. Kazlauskas, Dr. K. Olechnovič.
Other researcher: K. Timinskas.
System administrator: R. Dičiūnas.

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

RESEARCH PROJECTS CARRIED OUT IN 2017

Projects Supported by University Budget

Computational Studies of Protein Structure, Function and Evolution. Dr. Č. Venclovas. 2017–2019.

In 2017, 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. V. Siksnys) and archaeo-eukaryotic primases in bacterial genomes (jointly with Dr. Mart Krupovic at Institut Pasteur, Paris).

Main publications:

Olechnovič, K., Venclovas, Č. 2017. VoroMQA: Assessment of protein structure quality using interatomic contact areas. Proteins, vol. 85, p. 1131–1145.

Kazlauskiene, M, Kostiuk, G, Venclovas, Č, Tamulaitis, G, and Siksnys, V. 2017. A cyclic oligonucleotide signaling pathway in type III CRISPR-Cas systems. Science, vol. 357, p. 605–609.

Dapkūnas, J., Timinskas, A., Olechnovič, K., Margelevičius, M., Dičiūnas, R., Venclovas, Č. 2017. The PPI3D web server for searching, analyzing and modeling protein-protein interactions in the context of 3D structures. Bioinformatics, vol. 33, p. 935–937.

National Research Projects

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. Č. Venclovas. 2017–2020.

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 Vilnius University Institute of Biotechnology (Lithuania)
Institute of Molecular and Cell Biology, University of Tartu (Estonia)
Institut Pasteur, Département de Microbiologie, Paris (France)

OTHER SCIENTIFIC ACTIVITIES

Dr. Č. Venclovas –

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

INSTITUTE OF BIOCHEMISTRY

7 Sauletekio av., LT-10257

Tel. 223 4378

E-mail:

http://www.bchi.vu.lt

Director - Dr. Kastis Krikštopaitis

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 DEFENDED IN 2017

E. Šimoliūnas. Construction of self-assembling nanostructures based on structural proteins of bacteriophages.

Šakinytė. Reagentless enzymatic systems consisting of carbonaceous structures.

T. Ragaliauskas. Immobilization of lipid membranes on the planar surfaces. Surface plasmon resonance study.

MAIN SCIENTIFIC ACHIEVEMENTS IN 2017

Dagys M., A. Laurynėnas, D. Ratautas J. Kulys, R. Vidžiūnaitė, M. Talaikis, G. Niaura, L. Marcinkevičienė, R. Meškys, S. Shleev. 2017. Oxygen electroreduction catalysed by laccase wired to gold nanoparticle via trinuclear copper cluster. Energy&Environmental Science, 10: 498-502. IF 29.518.

Habil. Dr. V. Razumas and Dr. G. Valinčius were awarded the Lithuanian Science Prize (2016) for the series of works: Bioanalogical self-assembling systems of 2D and 3D structures: synthesis, properties and practical application (2001–2015).

DEPARTMENT OF BIOANALYSIS

7 Sauletekio av., LT-10257

Tel. 223 4389

E-mail:

Head – Prof. Habil. Dr. Valdas Stanislovas Laurinavičius

STAFF

Chief research fellows, professors: Habil. Dr. V. Laurinavičius (part-time), Habil. Dr. V. Razumas (part-time).
Senior research fellows: Dr. J. Razumienė, Dr. R. Šimkus, Dr. R. Vidžiunaitė.
Research fellows: Dr. L. Tetianec, Dr. M. Dagys.
Junior research fellows: Dr. I. Šakinytė, I. Bratkovskaja, V. Gurevičiene, A. Laurynėnas.
Doctoral students: J. Gružauskaitė, D. Ratautas, L. Rekovič, I. Jurkevičiūtė, M. Butkevičius.

Assistants: A. Jonuška, N. Baluckienė, L. Giniotienė, J. Matulevič.

RESEARCH INTERESTS

Investigation of bioelectrochemical properties of biomolecules
Investigation of electron transport in biomolecules
Creation of biosensors and bioreactors
Investigation of the mechanism of action of biomolecules and cells in heterogeneous systems and mathematical modeling
Whole-cell biosensors, bacterial self-organization, biofilms

RESEARCH PROJECTS CARRIED OUT IN 2017

Project Supported By University Budget

Design and Investigation of New Systems for Biocatalysis. Prof. Habil. Dr. V. Laurinavičius. 2017–2020.

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 unique bioanode with quinohemo protein alcohol dehydrogenase undergoing a fast direct electron transfer on 4-aminothiophenol modified gold nanoparticles was constructed. The bioanode generated high current at low potential, and was able to oxidize both glycerol and glyceraldehyde thus demonstrating a two-step electrochemical oxidation. The bio-fuel cell with the laccase-based biocathode was fabricated to evaluate the efficiency of the bioanode.

Main publication:

Ratautas, D., Tetianec, L., Marcinkevičienė, L., Meškys, R., Kulys, J. 2017. Bioanode with alcohol dehydrogenase undergoing a direct electron transfer on functionalized gold nanoparticles for an application in biofuel cells for glycerol conversion. Biosensors Bioelectronics, vol. 98, p. 215–221; doi: https://doi.org/10.1016/j.bios.2017.06.048. IF 7.780

Creation of new electrochemical systems containing aromatic nitrogen compounds as mediators. The application of dehydrogenases in the conversion of organic compounds is very attractive for biocatalysis due to appropriate catalytic activity and substrate specificity of the enzymes. Conversion of N-hydroxy- compounds, alcohols and other substrates catalysed by oxidoreductases (laccases, peroxidases and quinoprotein dehydrogenases) was investigated. The catalytic activity of the enzymes in the process, influence of different factors (temperature, composition, metal salts and pH of buffer solution) on it and final products of the reactions were determined. However, for the successful use of dehydrogenases in bioconversion systems, effective schemes for in situ regeneration of the expensive cofactors must be created. N,N'-dimethyl-4,4'-azopyridinium methyl sulfate (MAZP) was characterized as an electron transfer mediator for oxidation reactions catalyzed by NAD⁺- and pyrroloquinoline quinone (PQQ)-dependent alcohol dehydrogenases. Considering the MAZP redox potential and its reactivity with dehydrogenases or their cofactors, the mediator can be used in bioconversion systems, biosensors and biofuel cells.

Main publication:

Tetianec, L., Chaleckaja, A., Kulys, J., Janciene, R. Marcinkeviciene, L., Meskiene, R., Stankeviciute, J., Meskys, R. 2017. Characterization of methylated azopyridine as a potential electron transfer mediator for electroenzymatic systems. Process Biochemistry, vol. 54, p. 41–48; doi: https://doi.org/10.1016/j.procbio.2017.01.006.

National Research Projects

Agency for Science, Innovation and Technology. Development of Carbamide Analyser for Measurements in Industrial Media (No. TPP-01-054, LSS-600000-1126). Dr. J. Razumienė. Partner – UAB Bioanalizės sistemos. 2017–2018.

The project is suited to create a device that directly measures concentration of urea in industrial fertilizer samples.

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

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

OTHER SCIENTIFIC ACTIVITIES

Prof. Habil. Dr. V. Laurinavičius –

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

Prof. Habil. Dr. V. Razumas –

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

Prof. Habil. Dr. J. Kulys –

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

DEPARTMENT OF BIOELECTROCHEMISTRY AND BIOSPECTROSCOPY

7 Saletekio av., LT-10257 Vilnius

Tel. 223 4394

E-mail:

Head – Dr. Gintaras Valinčius

STAFF

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

RESEARCH INTERESTS

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

RESEARCH PROJECTS CARRIED OUT IN 2017

Project Supported By University Budget

Spectroelectrochemical Studies of Biological Systems and their Models. Dr. G. Valinčius. 2016–2018.

Recently, we developed an affordable and reproducible methodology for the self-assembly of the surface tethered bilayer membranes (tBLMs). We showed that such tBLMs are capable of functionally reconstituting transmembrane proteins retaining their biological function. Membrane reconstituted proteins (peptides, oligomers) may be probed by surface-specific techniques, including surface plasmon resonance, vibrational spectroscopies and atomic force microscopy. Fine structural details revealing the molecular geometry of tBLMs are evaluated using neutron reflectometry. The functional properties of both membranes and reconstituted protein complexes are accessible by electrochemical impedance spectroscopy (EIS). The theoretical framework of EIS developed in our group allows a detailed analysis of protein membrane interactions as well as applications of tBLMs for bioanalysis.

Main publications:

Ragaliauskas, T., Mickevicius, M., Rakovska, B., Penkauskas, T., Vanderah, D.J., Heinrich F., Valincius, G. 2017. Fast formation of low-defect-density tethered bilayers by fusion of multilamellar vesicles. BBA-Biomembranes, vol. 1859 (5), p. 669–678.

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

Griffin, S., Preta, G., Sheldon, I.M. 2017. Inhibiting mevalonate pathway enzymes increases stromal cell resilience to a cholesterol-dependent cytolysin. Sci Rep., vol. 7(1), p. 17050.

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

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

OTHER SCIENTIFIC ACTIVITIES

Dr. G. Valinčius –

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

Habil. Dr. G. Niaura –

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

Dr. R. Budvytytė –

member of the American Biophysical Society.

DEPARTMENT OF BIOLOGICAL MODELS

7 Sauletekio av., LT-10257 Vilnius

Tel. 223 4408

E-mail:

Head – Dr. Virginija Bukelskiene

STAFF

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

RESEARCH INTERESTS

Laboratory animals, cell culture, stem cells, tissues engineering

RESEARCH PROJECTS CARRIED OUT IN 2017

Project Supported by University Budget

Development of the Cell Technologies for Regenerative Medicine and their Evaluation on Biological Models. Dr. V. Bukelskienė. 2014–2018.

Study of cell interactions with scaffolds of different chemical composition and topography. It was found that primary rat dental pulp-derived stem cells adhesion was not affected by surface topography (wavy and microporous), but only determined by chemical composition of scaffolds. Nevertheless, due to a greater surface area to settle, wavy scaffolds were more favorable for cells to adhere. Furthermore, the 3D surface increased cell proliferation, but its microstructure pattern had negligible effect on cell multiplication rate. Focal adhesion kinase and Akt kinase expression and activity was also examined depending on the surface 3D structure.

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

Investigation of cell osteogenic differentiation molecular mechanisms depending on the pattern of surface 3D structure was conducted using primary rat dental pulp stem cells and rat periosteal-derived cells. Wavy and microporous 3D scaffolds were fabricated from polylactic acid. Alizarin Red S staining did not reveal any remarkable differences in the rate of induced and spontaneous osteogenic differentiation. However, alikaline phosphatase activity depended both on the cell type and surface structure. Moreover, surface structure-dependent gene expression was identified in the tested cells during osteogenic differentiation.

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

Novel biocompatible films based on UV curable hydrophilic copolymers containing siloxane units were prepared. These films exhibit good wettability due to hydrophilic units of copolymer, good biocompatibility 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.

Co-culture of different cell types more accurately represents the structure of real tissue and the cellular interactions within. Therefore, the novel type of co-culture based on rat endothelial progenitor cells and rat myogenic progenitor cells was developed.

International Research Project

COST Action CA16119: In Vitro 3-D Total Cell Guidance and Fitness (Cellfit). Dr. D. Baltriukienė. 2017–2021.

Contractual Research

To assess feed additives toxicity by using laboratory mice; UAB Centrinis parkas; Dr. V. Bukelskienė.

Study of the efficiency of feed additive; UAB Insectum, Dr. V. Bukelskienė.

Study of mice feed efficiency, UAB Sinsila, Dr. V. Bukelskienė.

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

Laser Research Centre , Faculty of Physics, Vilnius University (Lithuania)
Faculty of Chemistry, Vilnius University (Lithuania)
Faculty of Medicine, Vilnius University (Lithuania)
Centre of Heart Surgery, Hospital Santaros klinikos, Vilnius University (Lithuania)
Institute of Odontology, Faculty of Medicine, Vilnius University (Lithuania)
Department of Chemistry and Bioengineering, Faculty of Fundamental Sciences, Vilnius Gediminas Technical University (Lithuania)
CC Thermo Fisher Scientific Baltics
CC Prodentum
CC Centrinis parkas
CC Insectum
CC Sinsila

OTHER SCIENTIFIC ACTIVITIES

Dr. D. Baltriukienė –

President of Baltic Laboratory Animal Science Association, http://www.baltlasa.gf.vu.lt;
board member of the FELASA (Federation of European Laboratory Animal Science Associations), http://www.felasa.eu/;
board member of the Lithuanian Stem Cell Researchers Association, http://www.stemcell.lt/;
member of the Lithuanian Biochemical Society.

Dr. V. Bukelskienė –

board member of Baltic Laboratory Animal Sciensce Association, http://www.baltlasa.gf.vu.lt;
board member of FELASA (Federation of European Laboratory Animal Science Associations), http://www.felasa.eu/;
scientific supervisor of the Extramural School of Young Biochemists at Lithuanian Centre of Non-formal Youth Education, http://www.lmnsc.lt/lt/jaunuju_biochemiku_mokykla;
member of the Lithuanian Biochemical Society.

DEPARTMENT OF MOLECULAR CELL BIOLOGY

7 Sauletekio av., LT-10257 Vilnius

Tel. 223 4409

E-mail:

Head – Prof. Dr. Rūta Navakauskienė

STAFF

Chief research associate: Prof. Dr. R. Navakauskienė.
Senior research fellow: Dr. V. V. Borutinskaitė, Dr. A. Kalvelytė.
Research fellows: Dr. A. Imbrasaitė, Dr. J. Savickienė, Dr. G. Treigytė.
Junior research fellow: Dr. N. Krestnikova.
Doctoral students: S. Baronaitė, M. Glemžaitė, A. Stulpinas, A. Zentelytė, G. Valiulienė, A. Virkšaitė.

RESEARCH INTERESTS

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

RESEARCH PROJECTS CARRIED OUT IN 2017

Projects Supported by University Budget

Studies of Regulatory Mechanisms of Cancer and Stem Cell for New Technologies of Personalized Medicine. Prof. R. Navakauskienė. 2014–2018.

Assessement of changes in epigenetic landscape in stem and cancer cells during ageing.

We investigated the potential of epigenetic modulators EGCG and BIX-01294 to alter epigenetic state and cause cellular senescence in acute (NB4) and chronic (K562) myeloid leukemia cells. We have shown that after leukemia cell treatment with EGCG and BIX-01294 the proliferation and survival were inhibited of both cell lines. Both epigenetic modulators caused cell cycle arrest as assessed by gene (p53, p21, Rb) expression and flow cytometry analysis. Increased levels of ATM, HMGA2, phosphorylated ATM, and SA-β-galactosidase staining indicated that EGCG caused cellular senescence, whereas BIX-01294 did not. We observed that epigenetic players, such as DNMT1, HP1α, H3K9me3, EZH2, and SUZ12 are modulated.

We have also analyzed the epigenetic environment in terms of histone modifications in cultures of mesenchymal stem cells (MSCs) derived from human amniotic fluid (hAF) of normal pregnancies and those with fetal abnormalities.

Main publications:

Navakauskienė, R. 2017. Combination epigenetic therapy. In: Handbook of Epigenetics. The New Molecular and Medical Genetics. 2nd Ed. (Tollefsbol, T.O., ed.). Elsevier, Chapter 41, p. 623–632.

Borutinskaitė, V., Virkšaitė, A., Gudelytė, G., Navakauskienė, R. 2017. Green tea polyphenol EGCG causes anti-cancerous epigenetic modulations in acute promyelocytic leukemia cells. Leuk Lymphoma, vol. 59(2), p. 469–478. doi: 10.1080/10428194.2017.1339881. Epub 2017 Jun 22.

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

Main publication:

Kalvelytė, A. V., Imbrasaitė, A., Krestnikova, N., Stulpinas, A. 2017. Adult stem cells and anticancer therapy. In: Advances in Molecular Toxicology (James C. Fishbein, Jacqueline M. Heilman, eds.), p. 123–202; doi: 10.1016/B978-0-12-812522-9.00004-X.

NATIONAL RESEARCH PROJECTS

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

The aim of the project - to investigate the molecular factors and their role in human hematopoietic system and leukemia cell differentiation, regeneration and aging processes. The genomic and epigenetic studies in leukemia patients (in diagnosis, follow-ups and relaps) and the leukemia model systems are under investigation and we assess the molecular factors relevant to cell aging and cancer induction. Scientific value of the project - the new molecular factors involved in the regulation of aging of hematopoietic system will be defined. The practical value of the project - the obtained data will provide new opportunities for leukemia therapy; improve early diagnosis and cancer treatment.

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

Project goal – to investigate the regulatory role of epigenetic factors – DNA methylation, chromatin histones modifications, polycomb complex and microRNA, in the determination of amniotic stem cell fate – the potential of the growth and differentiation into cell types and death. For the study, we use the amniotic fluid after amniocentesis from normal donors and donors with genetic abnormalities of the fetus. We determine the proliferative and multipotent differentiation capacities of amniotic stem cells dependently on the risk of a donor age, the gestational time, the fetus pathology, and evaluate the functioning of epigenetic components of the stem cell regulatory network.

Main publications:

Valiulienė, G, Stirblytė, I, Jasnauskaitė, M, Borutinskaitė, V, Navakauskienė, R. 2017. Anti-leukemic effects of HDACi Belinostat and HMTi 3-Deazaneplanocin A on human acute promyelocytic leukemia cells. Eur J Pharmacol., vol. 799, p. 143–153; doi: 10.1016/j.ejphar.2017.02.014. Epub 2017 Feb 10.

Savickienė, J, Matuzevičius, D, Baronaitė, S, Treigytė, G, Krasovskaja, N, Zaikova, I, Navakauskas, D, Utkus, A, Navakauskienė, R. 2017. Histone modifications pattern associated with a state of mesenchymal stem cell cultures derived from amniotic fluid of normal and fetus-affected gestations. J Cell Biochem, vol. 118(11), p. 3744–3755; doi: 10.1002/jcb.26022. Epub 2017 May 30.

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. Navakauskienė. 2014–2018.

COST action CA15138: European Network of Multidisciplinary Research and Translation of Autophagy knowledge (TRANSAUTOPHAGY). Dr. V. Borutinskaitė. 2015–2019.

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

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

OTHER SCIENTIFIC ACTIVITIES

Prof. R. Navakauskienė –

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

Dr. A. V. Kalvelytė –

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

Dr. V. Borutinskaitė –

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

Dr. A. Imbrasaitė –

member of Federation of European Biochemical Society.

Dr. N. Krestnikova –

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

PhD students S. Baronaitė, M. Gasiūnienė, A. Stulpinas, A. Virkšaitė, A. Zentelytė:

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

DEPARTMENT OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY

7 Sauletekio av., LT-10257 Vilnius

Tel. 223 4386

E-mail:

Head – Dr. Rolandas Meškys

STAFF

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

RESEARCH INTERESTS

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

RESEARCH PROJECTS CARRIED OUT IN 2017

Projects Supported By University Budget

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

Bacterial indole degradation 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 indole biodegradation in Acinetobacter sp. strain O153 has been carried out. Catabolic cascade was reconstituted in vitro with recombinant proteins and each protein was assigned an enzymatic function. This work provides the first insights into genetic background of microbial indole biodegradation.

A number of unique novel phages have been isolated and investigated. One of those, Arthrobacter myovirus vB_ArtM-ArV1, seems to occupy a somewhat intermediate position between myo- and siphoviruses thus offering a glimpse into the evolution of tailed viruses.

Main publications:

Kaliniene, L., Šimoliūnas, E., Truncaitė, L., Zajančkauskaitė, A., Nainys, J., Kaupinis, A., Valius, M., Meškys R. 2017. Molecular analysis of Arthrobacter myovirus vB_ArtM-ArV1: we blame it on the tail. J. Virol. 2017 91: e00023-17. doi:10.1128/JVI.00023-17.

Sadauskas, M, Vaitekūnas, J, Gasparavičiūtė, R, Meškys, R. 2017. Indole biodegradation in Acinetobacter sp. strain O153: genetic and biochemical characterization. Appl. Environ. Microbiol. 2017 83 (19): e01453-17doi:10.1128/AEM.01453-17.

National Research Projects

Research Council of Lithuania. Novel Prodrug Activation Systems for Cancer Genotherapy (No. SEN-07/2015). Dr. J. Urbonavičius. 2015–2018.

Aim of the project is to develop prodrugs and their activating enzymes applicable for cancer therapy. Novel enzymes active towards the modified nucleobases were isolated and tested as a prodrug activating catalysts.

Main publication:

Aučynaitė, A., Rutkienė, R., Gasparavičiūtė, R., Meškys, R., Urbonavičius, J. 2017. A gene encoding a DUF523 domain protein is involved in the conversion of 2-thiouracil into uracil. Environ. Microbiol. Rep.; doi: 10.1111/1758-2229.12605.

Research Council of Lithuania. Screening and Analysis of Novel Enzymes Participating in Catabolism of Modified Uracil Base and Nucleosides (No. MIP-103/2015). Dr. J. Urbonavičius. 2015–2017.

Aim of the project is to search for the enzymes participating in catabolism of nucleobases and respectives nucleosides. Novel enzymes were isolated and their enzymatic activity was tested.

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

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, more than ten novel enterobacteria phages have been isolated. The effect of temperature on the efficiency of plating test revealed that one of these newly isolated phages, bacteriophage NBD2, has a low-temperature plating profile. With an optimum temperature for plating around 20°C, NBD2 efficiently produced plaques in a temperature range of 10 to 30 °C, yet failed to plate at temperatures above 35 °C. Since such physiological property proved NBD2 to be of interest in studying the cold-adaptation of viruses, the complete genome sequence of this phage was determined and analyzed.

Main publication:

Kaliniene, L., Truncaitė, L., Šimoliūnas, E., Zajančkauskaite, A., Vilkaitytė, M., Kaupinis, A., Skapas, M., Meškys, R. 2017. Molecular analysis of the low-temperature Escherichia coli phage vB_EcoS_NBD2. Arch. Virol.; doi:10.1007/s00705-017-3589-5.

Research Council of Lithuania. Bacteriophage Control of Nitrogen Cycling in Cyanobacteria: from Cells to Community (No. P-MIP-17-6). Dr. S. Šulčius (Nature Research Center), work package leader Dr. E. Šimoliūnas. 2017–2019.

Filamentous cyanobacteria have an important role in nitrogen cycling in the Baltic Sea, and it could be expected that viruses infecting these cyanobacteria would affect 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.

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. Šulčius (Nature Research Center), work package leader Dr. E. Šimoliūnas. 2017–2019.

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’s) 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.

Research Council of Lithuania. The Role of Atmospheric Nitrogen Fixation in the Largest Eutroficated European Lagoon (No. S-MIP-17-7). Dr. M. Žilius (Klaipėda University), work package leader Dr. R. Stanislauskienė. 2017–2020.

The aim of this project is to evaluate the contribution of pelagic N₂ fixation to systematic nitrogen budget and community functioning in water column, linking process rates, functional genes and model simulation in low-salinity estuary. The main tasks are: i) to quantify the abundance of functional marker genes (nifH, encoding nitrogenase reductase) and its transcripts as indicators of genetic potential for N fixation and ii) to identify diversity of nitrogen fixers through the analysis of nifH marker genes contained in the pelagic microbial community structure.

Research Council of Lithuania. Research and Practical Applications of a Type I‐F CRISPR‐Cas System (No. S-MIP-17-47). Dr. G. Tamulaitienė (Institute of Biotechnology, Life Sciences Center, VU), participant - Dr. L. Truncaitė (Institute of Biochemistry, Life Sciences Center, VU). 2017–2020.

Bacterial CRISPR–Cas immunity systems have proved as the efficient genome-editing tools in various organisms. However, genome editing of lytic bacteriophages appeared to be complicated because of their resistance mechanisms. The aim of this project is to adapt new CRISPR-cas systems for the genome engineering of less-studied phages. For this, lytic coliphages having either modified (VR5, RB69), or unmodified (RB49, VpaE1) DNA genomes have been selected, and the recombinant plasmids required for the editing of their essential and non-essential genes have been constructed.

International Projects

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

The main focus is the development of the innovative enzyme-screening techniques, involving the construction of tailored microorganisms and the synthesis of smart substrates. A screening system for hydrolases based on acylated uridines was established by using E. coli strains harboring pyrFEC mutations. The metagenomic libraries were tested (approx. 3,000,000 clones) and >30 colonies expressing various esterases were selected.

Contractual Research

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

Development of Methods for Elimination of Gliadin-Based Peptides from Protein Mixtures. AB Amilina, Lithuania. Dr. R. Meškys.

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

Centre for Physical Sciences and Technology (Lithuania)
Nature Research Centre (Lithuania)
Bayer Technology Services GmbH (Germany)

DEPARTMENT OF XENOBIOTICS BIOCHEMISTRY AND SCIENTIFIC INFORMATION

7 Sauletekio av., LT-10257 Vilnius

Tel. 223 4392

E-mail:

Heads – Habil. Dr. Narimantas Čėnas

STAFF

Chief research fellow: Habil. Dr. N. Čėnas.
Senior research fellows: Dr. Ž. Anusevičius, Dr. K. Krikštopaitis, Dr. J. Šarlauskas.
Research fellows: Dr. L. Kosychova, Dr. A. Marozienė, Dr. L. Misevičienė.
Junior research fellow: E. Polmickaitė-Smirnova.
Doctoral students: B. Valiauga, M. Lesanavičius.

RESEARCH INTERESTS

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

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

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

The studies of redox reactions of flavo-heme, flavo-sulfo, and flavo-sulfo-selenium enzymes possibly participating in the bioreductive activation of quinoidal and nitroaromatic compounds.

RESEARCH PROJECTS CARRIED OUT IN 2017

Project Supported By University Budget

Molecular Mechanisms of Enzymatic Activation, Detoxification, Biodegradation, and Cytotoxicity of Redox Active Xenobiotics. Habil. Dr. N. Čėnas. 2017–2020.

The preliminary kinetic characterization of human mitochondrial and cytosolic thioredoxin reductases with quinoidal electron acceptors has been carried out. The midpoint reduction potential of E. coli oxygen-insensitive nitroreductase A (NfsA), -0.215 V, was determined. It was found that during the photoreduction of NfsA the transient flavin semiquinone intermediate was not formed. Like in reduction of nitroaromatic compounds by NfsA, their antimicrobial activity against E. coli increased with an increase in their single-electron reduction potential, following the same trend as the classical nitrofuran antibiotics. The mode of inhibition of Plasmodium falciparum glutathione reductase by nitroaromatic compounds was detalized, showing significant differences with that of human erythrocyte enzyme. The kinetic characteristics of reactions of P. plasmodium ferredoxin reductase, a possible target of antimalarial chemotherapy, with nitroaromatic and inorganic electron acceptors were obtained, showing similarity with the previously investigated Anabaena sp. enzyme.

Main publications:

Šarlauskas, J., Tamulienė, J., Čėnas, N. 2017. Aziridinyl-substituted benzo-1,4-quinones: A preliminary investigation on the theoretical and experimental studies of their structure and spectroscopic properties. Spectrochimica Acta. Pt. A., vol. 178, p. 136–141.

Pečiukaitytė-Alksnė, M., Šarlauskas, J., Misevičienė, L., Marozienė, A., Čėnas, N., Krikštopaitis, K., Staniulytė, Z., Anusevičius, Ž. 2017. Flavoenzyme-mediated reduction reactions and antitumor activity of nitrogen-containing tetracyclic ortho-quinones and their nitrated derivatives. EXCLI Journal, vol. 16, p. 663–678.

Valiauga, B., Williams, E.M., Ackerley, D.F., Čėnas, N. 2017. Reduction of quinones and nitroaromatic compounds by Escherichia coli nitroreductase A (NfsA): Characterization of kinetics and substrate specificity. Archives of Biochemistry and Biophysics, vol. 614, no. 1, p. 14–22.

International Research Projects

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

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

Bilateral Lithuanian-Ukraine programme Investigation of L- and D-lactate: Cytochrome с Oxidoreductases Isolated from the Recombinant Yeast Hansenula Polymorpha and their Usage for Construction of Amperometric Biosensors (No. TAP LU 03/2014). Dr. K. Krikštopaitis. 2014–2015.

A paper on the development of biosensor for L-lactate performed in the frame of this project appeared in 2017:

Smutok O., Karkovska M., Serkiz R., Vus B., Čėnas N., Gonchar M. 2017. A novel mediatorless biosensor based on flavocytochrome b₂ immobilized onto gold nanoclusters for non-invasive L-lactate analysis of humain liquids. Sensors and Actuators B – Chemical., vol. 250, p. 469–475.

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 Mokslininku str., LT-08662 Vilnius

Tel.: 272 9058

E-mail:

Head – Dr. Regina Jančienė

STAFF

Senior research fellow: Dr. R. Jančienė.
Research fellow: Dr. Z. Staniulytė.
Junior research fellow: Dr. R. Sirutkaitis.
Assistants: Dr. A. Klimavičius, D. Podėnienė, R. Rozenbergas, S. Palaikienė.

RESEARCH INTERESTS

Synthesis of heterocyclic, amino acid and polyether derivatives, design and development of technology of chemical processes, custom synthesis

RESEARCH PROJECTS CARRIED OUT IN 2017

Project Supported By University Budget

Investigation of the Synthesis and Structure of Modulators and Catalysts of Biological Processes Dr. R. Jančienė. 2017–2020.

Synthesis of model tetraethylene glycol derivatives bearing different α- and ω-substituents.

Mono-amino-TEG was prepared via sequence of 3 reactions: (1) synthesis of monomesyl-TEG, (2) synthesis of TEG 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 TEG bisalkylsulphonates were synthesized. Next, TEG-derivatives bearing α-amino and ω-alkylsulphonic acid moiety were synthesized.

Investigation of synthesis methods for sodium salts of ethylenglycolsulphonic acid.

With the aim to get target ethansuphonates of ethylenglycol, the sulphonation reaction of corresponding halo derivatives was investigated. Various catalysts (quaternary ammonium salts, Cu, etc) were used in mild conditions to synthesize sodium 2-chloro- or 2-bromoethansulphonates, which were further used for alkylation of different ethylenglycols.

Investigation and optimization of synthesis methods of fluorescence indole derivatives.

For the construction of indole ring, the metal-induced reductive heterocyclization reaction of 2-(2-nitrophenyl)-1-phenylethanones with different sudbstituents at the aromatic rings was used. The process of the reduction of nitro compounds to the corresponding amines was accomplished by a simultaneous N-heterocyclization leading to the corresponding 2-phenyl-1H-indole derivatives. The study of the reduction of nitroethanones was commenced under mild catalytic conditions (H2, Pd/C, Re/Ni).

Main publications:

Tetianec, L., Chaleckaja, A., Kulys, J., Janciene, R., Marcinkeviciene, L., Meskiene, R., Stankeviciute, J., Meskys, R. 2017. Characterization of methylated azopyridine as a potential electron transfer mediator for electroenzymatic systems. Process Biochemistry, vol. 54, p.41–48.

Pečiukaitytė-Alksnė, M., Šarlauskas, J., Misevičienė, L., Marozienė, A., Čėnas, N., Krikštopaitis, K., Staniulytė, Z., Anusevičius, Ž. 2017. Flavoenzyme-mediated reduction reactions and antitumor activity of nitrogen-containing tetracyclic ortho-quinone compounds and their nitrated derivatives. EXCLI Journal, vol. 16, p. 663–678.

National Research Projects

Agency for Science, Innovation and Technology. National Program to Support R&D Contracts, Invitation No. US04. Dr. R. Jančienė. 2017.

Research in development of new methods for making alfa-amino-omega-alkylsulfonic acid sodium salts of polyethylene glycols US-04-029

Investigation of synthesis of sodium 2-[2-[2-[2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethoxy]ethansulphonate and development of preparative technology US-04-022

Study of cyclization of p-cyano-o-nitrobenzyl-p-cyanophenylketone and the synthesis of experimental samples of DAPI dihydrochloide US-04-021

Study of optimization of synthesis of pantetine-4‘,4‘‘-diphosphate and other enzyme cofactors US-04-063

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

Contractual Research

Study of Synthesis Optimization of Pantetine-4,4-Diphosphate and Other Enzyme Cofactors. Contract with CC Thermo Fisher Scientific Baltics. Dr. R. Jančienė.

Investigation of Regeneration Conditions of Butylacetate and Negative Developer and Manufacturing of Their Experimental Batches. Contract with Uab Vilniaus Ventos Puslaidininkiai. Dr. A. Klimavičius.

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

Research in Development of New Methods For Making Alfa-Amino-Omega-Alkylsulfonic Acid Sodium Salts of Polyethylene Glycols. Contract with Ramidus Ab (Sweden). Dr. R. Jančienė.

Optimization of Synthesis Technology and Scaling of Production of 2-(4-Methoxy-Phenyl)-[1,3]Dithiane. Contract with Synthon Chemicals Gmbh (Germany). Dr. R. Jančienė.

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

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

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

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

PROTEOMICS CENTRE

7 Sauletekio av., LT-10257, Vilnius

Tel. 223 4410

E-mail:

Head – Dr. Mindaugas Valius

STAFF

Senior research fellow: Dr. M. Valius, Dr. J. Cicėnas.
Research fellow: Dr. A. Kaupinis.
Junior research fellow: Dr. M. Ger.
Doctoral students: N. Dreižė, S. Urnikytė, E. Žalytė.
Visiting scientist: P. Gupta.

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 2017

Project Supported by University Budget

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

Main publications:

Cicenas, J., Kvedaraviciute, K., Meskinyte, I., Meskinyte-Kausiliene, Skeberdyte, A. 2017. KRAS, TP53, CDKN2A, SMAD4, BRCA1, and BRCA2 mutations in pancreatic cancer. Cancers, vol. 9, No. 5, doi: 10.3390/cancers9050042.

Kaliniene, L., Šimoliūnas, E., Truncaitė, L., Zajanžkauskaitė, A., Nainys, J., Kaupinis, A., Valius, M., Meškys, R. 2017. Molecular analysis of Arthrobacter Myovirus vB_ArtM-ArV1: we blame it on the tail. Journal of Virology, vol. 91, no. 8; e00023-17.

National Research Projects

Research Council of Lithuania. High Throughput Proteomics for Cancer Cell Surface Protein Recognition by Quantum Dots (No. MIP-033/2014). Dr. M. Valius. 2014–2017.

We have generated a number of cell lines resistant to the novel anticancer drug RH1 and performed global differential high throughput proteomics analysis, cytoplasmic membrane proteome, phosphopeptide-enriched proteomics and searched for activated kinases by the novel multiplex kinase inhibitor beads assay. Bioinformatic analysis of this high content date allowed us to identify a number of possible mechanisms of cell resistant to the RH1 drug and highlighted the role of cancer stem-like cells in the drug resistance. We also performed large scale in silico RH1 target search based on RH1 and protein docking. Data revealed that several protein kinases are possible targets of this novel potent anti-cancer drug.

Main publications:

Gupta, P., Pramodkumar, Bastikar, A. Virupaksha, Kuciauskas, D., Kothari, Lal Shanker, Cicenas, J., Valius, M. 2017. Molecular modeling and structure-based drug discovery approach reveals protein kinases as off-targets for novel anticancer drug RH1. Medical Oncology, vol. 34, No. 10; doi: 10.1007/s12032-017-1011-5.

Cicenas, J., Tamosaitis, L., Kvedaraviciute, K., Tarvydas, R., Staniute, G., Kalyan, K., Meskinyte-Kausiliene, E., Stankevicius, V., Valius, M. 2017. KRAS, NRAS and BRAF mutations in colorectal cancer and melanoma. Medical Oncology, vol. 32, No. 2; doi: 10.1007/s12032-016-0879-9.

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

In this project, we have performed high throughput quantitative proteomic analysis of the chemotherapy‐sensitive and ‐resistant colorectal cancer (CRC) cell lines. Potential predictive biomarkers for FOLFOX therapy have been identified and currently undergoing validation on clinical material.

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, 2015–2018.

We perform high-throughput protein biomarkers discovery using already collected as well as collected in the frame of this project patients' pancreatic material. The potential biomarkers have been discovered and now undergoing validation on patients’ 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:

Stankevicius, V., Kunigenas, L., Stankunas, E., Kuodyte, K., Strainiene, E. Cicenas, J., Samalavicius, E. N., Suziedelis, K. 2017. The expression of cancer stem cell markers in human colorectal carcinoma cells in a microenvironment dependent manner. Biochemical and Biophysical Research Communications, vol. 484, No. 4, p. 726–733.

Contractual Research

Midbody Proteomics. Lithuanian University of Health Science, Institute of Cardiology, Dr. A. Skeberdis.

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

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

OTHER SCIENTIFIC ACTIVITIES

Dr. M. Valius –

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

INSTITUTE OF BIOSCIENCES

7 Saulėtekio av., LT-10257 Vilnius

Tel. 239 8200, fax 239 8204

www http://www.gf.vu.lt

Director – Prof. Habil. Dr. Juozas Rimantas 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 DEFENDED IN 2017

R. Rimgailė-Voicik. Organization and functioning patterns of Lycopodium L. and Diphasiastrum Holub populations with an emphasis on subterranean gametophytes and juvenile sporophytes in dry pine forests.

J. Butkuvienė. Batrachium in Lithuanian rivers: morphological and genetic diversity and related factors.

K. Daniūnaitė. Diagnostic and prognostic DNA methylation biomarkers of prostate cancer.

R. Pranckutė. Evaluation of lactic acid and thermophilic bacteria antibacterial activity and compatibility with prebiotic oligosaccharides for development of new synbiotics.

V. Valskys. The influence of conditions of sapropel formation on its chemical composition and contamination.

V. Linkuvienė. Observed and intrinsic thermodynamic and kinetic parameters of sulfonamide derivative binding to carbonic anhydrases.

V. Grajevskaja. Studying a role of TBX5A in zebrafish heart regeneration.

MAIN CONFERENCES ORGANIZED IN 2017

9th Conference of Lithuanian Neurosciences Association

The COINS

DEPARTMENT OF BIOCHEMISTRY AND MOLECULAR BIOLOGY

7 Saulėtekio av., LT-10257, Vilnius
Tel./fax 85 239 8226
E-mail:

Head - Prof. Dr. Edita Sužiedėlienė

STAFF

Professors: Dr. J. Kadziauskas, Dr. E. Sužiedėlienė, Dr. S. Serva, prof. V. Starkuvienė (part-time). K. Sužiedėlis (part-time).
Associate professors: Dr. E. Bakienė, Dr., D. Dabkevičienė, Dr. A. Markuckas, Dr. S. Sasnauskienė, Dr. A. Sasnauskienė, Dr. A. Zimkus.
Lecturers: Dr. V. Jonušienė, Z. Žitkus.
Senior research fellows: Dr. D. Labeikytė, J. Armalytė, Dr. A. Zimkus.
Research fellows: Dr. V. Jonušienė, Dr. A. Sasnauskienė.
Doctoral students: D. Jurėnas, A. Konovalovas, A. Mlynska, E. Kukcinavičiūtė, J. Skerniškytė, A. Mikalkėnas, J. Fadejeva, L. Kunigėnas, L. Aitmanaitė, R. Krasauskas.

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 2017

Projects Supported By University Budget

Investigation of Mechanisms of Cellular Homeostasis and their Clinical and Biotechnological Application. Prof. Dr. E. Sužiedėlienė, Prof. Dr. S. Serva, Assoc. Prof. A. Sasnauskienė.

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 novel resistance mechanisms 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:

Kukcinavičiūtė, E., Sasnauskienė, A., Dabkevičienė, D., et al. 2017. Effect of mTHPC-mediated photodynamic therapy on 5-fluorouracil resistant human colorectal cancer cells. Photochem Photobiol Sci, doi: 10.1039/c7pp00014f.

Jurėnas, D., Chatterjee, S., Konijnenberg, A. et al.. 2017. AtaT blocks translation initiation by N-acetylation of the initiator tRNAfMet. Nature Chemical Biology, doi:10.1038/nchembio.2346.

Jurėnas, D., Garcia-Pino, A., Van Melderen, L. 2017. Novel toxins from type II toxin-antitoxin systems with acetyltransferase activity. Plasmid,

doi: 10.1016/j.plasmid.2017.08.005.

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. Armalytė. Project leader Dr. M. Ružauskas. 2015–2018.

Research Council of Lithuania. New Markers for Personalized Therapy of Colorectal Cancer: Proteomics, Rnomics, Clinic. Dr. A. Sasnauskienė, Dr. V. Jonušienė. Project leader prof. A. Laurinavičius. 2015–2018.

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

Main publication:

Lukša, J., Ravoitytė, B., Konovalovas, A., et al. 2017. Different metabolic pathways are involved in response of saccharomyces cerevisiae to L-A and M viruses. Toxins (Basel), doi: 10.3390/toxins9080233.

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

Lithuanian University of Health Sciences (Lithuania)
Nature Research Center (Lithuania)
Heidelberg University (Germany)
Universite Libre de Brussels (Belgium)
University of Haifa (Israel)

OTHER SCIENTIFIC ACTIVITIES

Prof. E. Sužiedėlienė –

member of Research Council of Lithuania.

Prof. S. Serva –

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 Saulėtekio av., LT-10257 Vilnius
Tel. 239 8257
E-mail:

Head – Prof. Habil. Dr. Juozas Rimantas Lazutka

STAFF

Professors: Habil. Dr. J. R. Lazutka, Dr. S. Jarmalaitė, Dr. E. Kutorga, Dr. A. Lubys (part-time), Habil. Dr. J. R. Naujalis, Habil. Dr. I. Pašakinskienė (part-time), Habil. Dr. V. Rančelis (emeritus), Dr. G. Slapšytė, Dr. D. Žvingila.
Associate professors: Dr. T. Čėsnienė, Dr. J. Kostkevičienė, Dr. V. Morkūnas.
Assistants: Dr. I. Prigodina Lukošienė, Dr. K. Daniūnaitė, Dr. R. Šiukšta.
Junior assistant: K. Kvederavičiūtė.
Lecturers: S. Juzėnas, A. Meldžiukienė, Dr. E. Meškauskaitė, Dr. J. Rukšėnienė, Dr. J. Tupčiauskaitė, P. Venckus.
Senior research fellows: Dr. V. Kleizaitė, Dr. V. Morkūnas.
Research fellows: Dr. V. Dedonytė, Dr. J. Kazlauskaitė, Dr. D. Naugžemys, Dr. J. Patamsytė, Dr. V. Vaitkūnienė.
Junior research fellows: Dr. M. Rasimavičius, Dr. R. Rimgailė-Voicik, Dr. J. Rukšėnienė.
Doctoral students: A. Nestarenkaitė, G. Radvilienė, I. Sadzevičienė, A. Skeberdytė, A. Stumbrytė, K. Stuopelytė, P. Venckus, Ž. Kapustina, R. Kubiliūtė, D. Strepetkaitė, A. Žalimas.

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
Research of environmental impact on plant, fungi, algae biology, ecology and distribution
Inventorization and monitoring of rare, protected and alien species
Algal biotechnology
Fungal and lichen biogeography and systematics
Fungal and botanical biodiversity of selected territories, ecosystems and habitats
Composition, structure and dynamics of lichen and plant populations
Studies of historical fungal, algae, lichen and plant collections, maintained in the Herbarium of Vilnius University

RESEARCH PROJECTS CARRIED OUT IN 2017

Projects Supported by University Budget

Function, Variability and Genome Structure in Higher Eukaryotes. Prof. J. R. Lazutka, Prof. G. Slapšytė, Prof. S. Jarmalaitė. 2014–2018.

The genotoxic potential of naturally occurring polyphenols is evaluated using various assays. Antioxidant and genotoxic properties of hispidin were studied. DNA methylation, miRNA and gene expression are analyzed in malignant and nonmalignant human tissues. Genotoxicity of femtosecond 213nm nanosecond UV laser pulses on the DNA of murine bone marrow cells in vitro is investigated. Genome and proteome analysis of crustacean Daphnia pulex was carried out.

Main publications:

Smolskaitė, L., Slapšytė, G., Mierauskienė, J., Dedonytė, V., Venskutonis, P. R. 2017. Antioxidant and genotoxic properties of hispidin isolated from the velvet-top mushroom, Phaeolus schweinitzii (Agaricomycetes). International Journal of Medicinal Mushrooms, vol. 19(11) p. 967–980.

Demidenko, R., Daniunaite, K., Bakavicius, A., Sabaliauskaite, R., Jankevicius, F., Lazutka, J. R., Jarmalaite, S. 2017. Decreased expression of MT1E is a potential biomarker of prostate cancer progression. Oncotarget., vol. 8(37), p. 61709–61718; doi: 10.18632/oncotarget.18683.

Kettunen, E., Hernandez-Vargas, H., Cros, M. P., Durand, G., Le Calvez-Kelm, F., Stuopelyte, K., Jarmalaite, S., Salmenkivi, K., Anttila, S., Wolff, H., Herceg, Z., Husgafvel-Pursiainen. K. 2017. Asbestos-associated genome-wide DNA methylation changes in lung cancer. Int J Cancer., vol. 141(10), p. 2014–2029; doi: 10.1002/ijc.30897.

Plant Polymorphism, Genome Stability and its Changing Factors. Prof. Emeritus V. Rančelis, Prof. D. Žvingila. 2016–2020.

Genetic polymorphism is very important in the situation of the global climate change and is exploited in plant breeding. We studied DNA variability in the populations of Erigeron annuus, Bunias orientalis, Solidago canadensis, S. virgaurea and assessed changes in Vicia faba genome caused by genotoxic agents. 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. We also started research of fast evolutionary genomic changes that are caused by biological invasions. Our study revealed that the triggers of genetic instability in barley homeotic double mutants are tweaky spike-type mutations associated with an auxin imbalance in separate spike phytomeres.

Main publications:

Tunaitienė, V., Patamsytė, J., Naugžemys, D., Kleizaitė, V., Čėsnienė, T., Rančelis, V., Žvingila, D. 2017. Genetic and allelopathic differences between populations of daisy fleabane Erigeron annuus (L.) Pers. (Asteraceae) from disturbed and stable habitats. Biochemical Systematics and Ecology, vol. 70, p. 294–303 IF 0.929.

Šiukšta, R., Vaitkūnienė, V., Rančelis, V. 2017. Is auxin involved in the induction of genetic instability in barley homeotic double mutants? Planta, doi: 10.1007/s00425-017-2802-9; IF3.361.

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

Understanding how vegetation influences the development of the juvenile club moss population is crucial for establishing protection for these archaic plants. Non-metric multidimensional scaling was used to observe vegetation differences in nine sites with juvenile club moss populations. The research on current distribution, state of habitats and the size of populations of Equisetum telmateia (Equisetaceae) in Lithuania revealed the main threats and requirement for the conservation of this species. The main threats for E. telmateia are forest logging and changes in habitat hydrological regime, though wild animals, human activities and invasive plant species also have certain negative impact on the populations of this species. Species composition and indicative properties of Desmidiales epiphytic algal communities were analysed in the water of the Aukštumala and Girutiškis wetland complexes. The aim of experimental cultivation of green algae experimental cultivation of green algae is to investigate effect of total nitrogen and total phosphorus concentration in the wastewater as well as other environmental factors, such as light intensity, temperature and pH, impact on algae culture growth and its biomass biochemical composition. Distribution, substrates and status of fungal species alien and invasive to Lithuania were analysed. The field investigations on selected rare and threatened fungal species were carried out in the forests with different structure and management.

Main publications:

Gudžinskas, Z., Rasimavičius, M., 2017. Distribution, state and conservation of Equisetum telmateia in Lithuania. Botanica Lithuanica, vol. 23(1), p. 17–32.

Rimgailė-Voicik, R., Naujalis, J. R., 2017. Presence of juvenile club moss (Lycopodiaceae) sporophytes and gametophytes in relation to vegetation cover in dry pine forests. American Fern Journal, vol. 106(4), p. 242–257.

Venckus, P., Kostkevičienė, J. Bendikienė, V., 2017. Green algae Chlorella vulgaris cultivation in municipal wastewater and biomass composition. Journal of Environmental Engineering and Landscape Management, vol. 25(1), p. 56–63.

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. Čėsnienė. 2015–2018.

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 (RAPD, ISSR, isozymes) 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.

Main publication:

Čėsnienė, T., Kleizaitė, V., Bondzinskaitė, S., Taraškevičius, R., Žvingila, D., Šiukšta, R., Rančelis, V. 2017. Metal bioaccumulation and mutagenesis in a Tradescantia clone following long-term exposure to soils from urban industrial areas and closed landfills. Mutation Research - Genetic Toxicology and Environmental Mutagenesis, vol. 823, p. 65–72.

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

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 – 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 publication:

Butkuvienė, J., Sinkevičienė, Z., Naugžemys, D., Patamsytė, J., Žvingila, D. 2017. Genetic diversity of Batrachium (Ranunculaceae) species reveals the necessity of their protection in Lithuanian rivers. Aquatic Botany, vol. 142, p. 61–70.

Research Council of Lithuania. Impact of Clear Cuttings on Transformation of Biodiversity in Forest Ecosystems (MEKODINA), 2015–2018. No. SIT-1/2015. Participants of project Dr. E. Meškauskaitė, S. Juzėnas, Dr. R. Rimgailė-Voicik, A. Meldžiukienė.

This study aims to investigate the dynamic of forest soil chemical composition and soil microbiota and at determining variation ground vegetation and insects species. In order to determine the response of forest ecosystem components to drastic changes, the complex methods agrochemistry, entomology, chemistry, and geobotany will be applied.

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). 2016–2018.

Participant of project Dr. M. Rasimavičius.

During the project, bryophyte collections of the end of 19th century till the middle of the 20th century will be investigated. Their significance for bryophyte diversity in Lithuania will be assessed. The collections are supposed to maintain valuable material for the evaluation of the impact landscape changes on bryoflora structure of the country. The specimens of the collections will be identified and inserted into the main Herbaria to ensure their accessibility for the future scientific investigations. According to the herbaria data the localities of rare bryophyte species will be checked and the influence of landscape changes on the status of their populations and habitats will be revealed.

Research Council of Lithuania. Modern Technologies to Resolve a Complex Structure of Tumor (No. P-MIP-17-189). Prof. S. Jarmalaitė. 2017–2020.

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

Research Council of Lithuania. Molecular Tools for Prostate Cancer Follow-Up and Treatment Individualization (No. SEN-9/2016). Prof. F. Jankevičius. 2016–2018.

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 preliminary 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.

Main publication:

Daniunaite, K., Dubikaityte, M., Gibas, P., Lazutka, J. R., Bakavicius, A., Ulys, A., Jankevicius, F., Jarmalaite, S. 2017. Clinical significance of microRNA host gene promoter methylation in prostate cancer. Hum Mol Genet., vol. 26(13), p. 2451–2461; doi: 10.1093/hmg/ddx138.

Contractual Research

Research project sponsored by Joint-stock company “Fortum Klaipėda”. Cultivation of Algae Haematococcus Pluvialis and Optimization of Dry Biomass Exclusion (No: TPS-600000-1761). Participant of the project P. Venckus. 2017–2018.

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

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

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

OTHER SCIENTIFIC ACTIVITIES

Prof. E. Kutorga –

editor-in-chief 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. Lazutka –

deputy editor-in-chief the journal Biologija (Biology);
editor of the journal Open Life Sciences (formerly Central European Journal of Biology).

Prof. J. R. Naujalis –

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

Prof. V. Rančelis –

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

DEPARTMENT OF MICROBIOLOGY AND BIOTECHNOLOGY

7 Saulėtekio al., LT-10257 Vilnius
Tel. 239 8205
E-mail:

Head - Prof. Dr. Lilija Kalėdienė

STAFF

Professors: Dr. L. Kalėdienė, Dr. N. Kuisienė, Dr. A. Meškauskas.
Associate professors: Dr. I. Girkontaitė, Dr. E. Lastauskienė.
Assistants: Dr. A. Gegeckas, Dr. R.Gudiukaitė.
Lecturers: Dr. J. Raugalas, R. Puzirauskas, dr. R. Kananavičiūtė, R. Petkauskaitė,
Junior research fellow: V. Norkūnas.
Specialists: J. Lekavičiūtė, R. Jurkevičienė.
Doctoral students: A. Kaunietis, A. Gricajeva, I. Burneikienė, T. Kazanova, R. Bikmurzinas, J. Lebedeva, T. Kirtiklienė, J. Jurgelevičiūtė.

RESEARCH INTERESTS

Genomics and biotechnologies: fundamental and applied microbial research.

Research of microorganisms for innovative biotechnologies

Biocatalysts selection for biomass conversion

Procaryotes for biotechnology, biopharmacy efficiency and safety food production development

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 2017

Projects Supported by University Budget

Selection of Micro-Organisms and Researches for Innovative Biotechnology Creation. Prof. Dr. L. Kalėdienė.

Work objective: Selection of microorganisms in order to create an effective biocatalysts for the development of biotechnology in the environment.

Main publication:

Gricajeva, A., Kazlauskas, S., Kalėdienė, L., Bendikienė, V. 2017. Analysis of Aspergillus sp. lipase immobolozation for the application in organic synthesis. International Journal of Biological Macromolecules, doi.org/10.1016/j.ijbiomac.2017.11.010.

Molecular Prokaryote Microbiology for Modern Biotechnology and Biopharmacy. Prof. Dr. N. Kuisienė.

Work objective: Using modern methods of molecular prokaryotic microbiology to develop the new products for biotechnology and biofarming needs.

Main publication:

Petkauskaite, R., Blom, J., Goesmann, A., Kuisiene, N. 2017. Draft genome sequence of pectic polysaccharide-degrading moderate thermophilic bacterium Geobacillus thermodenitrificans DSM 101594. Braz. J. Microbiol., vol. 48(1), p. 7–8.

Engineering of Micro-Organism Cells and Treatments and Biotechnological Application Research. Dr. E. Lastauskienė.

Work objective:Evaluation of genetic factors and protein structural elements for microorganism cells and specificity of enzymes.

Main publication:

Simonis, P., Kersulis, S., Stankevich, V., Kaseta, V., Lastauskiene, E., Stirke, A. 2017. Caspase dependent apoptosis induced in yeast cells by nanosecond pulsed electric fields. Bioelectrochemisty, doi: 10.1016/j.bioelechem.2017.01.05. IF 3.346.

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). 2016–2018.

Main publications:

Novickij, V., Lastauskienė, E., Švedienė, J., Grainys, A., Staigvila, G., Paškevičius, A., Girkontaitė, I., Zinkevičienė A., Markovskaja, S., Novickij, J. 2017. Membrane permeabilization of pathogenic yeast in alternating sub-microsecond electromagnetic fields in combination with conventional electroporation. Jour Membr Biol., doi: 10.1007/s00232-017-9951-4.

Novickij, V., Girkontaitė, I., Zinkevičienė, A., Švedienė, J., Lastauskienė, E., Paškevičius, A., Markovskaja, S., Novickij, J. 2017. Reversible permeabilization of cancer cells by high sub-microsecond magnetic field. IEEE Transactions on Magnetics, vol. 53, iss. 11; doi: 10.1109/TMAG.2017.2719699.

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). 2017–2020.

Applied Research and Experimental Development No. APS-140000-2149. Innovative Check Nr. 43V-1082017.

Contractual Research

Cultivation of Haematococcus Pluvialis and the Optimization of Dry Biomass Release. CJSC FORTUM Klaipėda. 2017–2018.

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

Thompson Rivers University (Canada)

OTHER SCIENTIFIC ACTIVITIES

Prof. Dr. L. Kalėdienė –

President of Lithuania’s Society of Microbiologists;
Chairman of Master and Bachelor Microbiology and Biotechnology study program;
member of Lithuania’s Genetically Modified Organisms Experts Committee.

Prof. Dr. N. Kuisienė –

vice president of Lithuania’s Society of Microbiologists;
member of Biology PhD committee; Member of Master and Bachelor Microbiology and Biotechnology study program.

Dr. E. Lastauskiene, Dr. A. Gegeckas –

Board members of Lithuania’s Society of Microbiologists,
members of Master and Bachelor Microbiology and Biotechnology study program

DEPARTMENT OF NEUROBIOLOGY AND BIOPHYSICS

7 Saulėtekio av., LT-10257 Vilnius
Tel. 239 8222,
E-mail:

Head - Prof. Dr. Osvaldas Rukšėnas

STAFF

Professors: Dr. A. Alaburda, Dr. D. Matulis (part-time), Dr. O. Rukšėnas.
Associate professors: Dr. V. Bukelskienė (part-time), Dr. R. Grikšienė, Dr. I. Griškova-Bulanova, Dr. V. Kisnierienė, Dr. V. Sakalauskas, Dr. G. Svirskis (part-time), Dr. V. Vengelienė (part-time).
Lecturers: Dr. R. Buišas, A. Daktariūnas, R. Grigonis.
Senior research fellows: Dr. I. Griškova-Bulanova, Dr. V. Sakalauskas.
Research fellow: Dr. V. Kisnierienė.
Junior research fellows: A. Daktariūnas, A. Voicikas.
Doctoral students: D. Dankin, Ž. Lukošius, A. Šlėktaitė, L. Mažrimaitė, V. Morkūnaitė, R. Grigonis, E. Janėnaitė, M. Baranauskas, D. Leščiūtė-Krilavičienė, I. Lapeikaitė, A. Kalnaitytė, A. Voicik, S. Mėlynytė, R. Mončiunskaitė, T. Paulauskas, E. Pipinis, V. Parčiauskaitė, R. Dulinskas, S. Venclovė, V. Survilienė.

RESEARCH INTERESTS

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

RESEARCH PROJECTS CARRIED OUT IN 2017

Projects Supported By University Budget

Theoretical, Electrophysiological and Psychophysical Investigation of Information Coding and Processing. Prof. O. Rukšėnas. 2016–2020.

During mental rotation task oral contraceptives users were less accurate than NC women and men

Adaptation to unambiguously oriented figure results in a percept of opposite orientation

The heart-rate evoked potential amplitudes during 400–545 ms window after the R peak correlated to the "Not-Worrying" about body sensations

Asparagine increases AP amplitude, prolongs action potential repolarization in Nitellopsis obtusa cells, tonoplast of these cells is more permeable to Cs¹³⁷ than the plasmalemma

Recovery from action potential threshold depolarization in motoneurons from turtle spinal cord can be described by exponential law

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 Universtity of Technology (New Zealand)
Valparaiso University (Chile)
National Institute of Mental Health (Czech Republic)

OTHER SCIENTIFIC ACTIVITIES

Prof. A. Alaburda –

member of the Lithuanian Society for Neurosciences.European Commission expert.

Dr. R. Buišas –

member of the Lithuanian Society for Neurosciences.

Assoc. Prof. I. Griškova-Bulanova –

member of the Lithuanian Society for Neurosciences.

Assoc. Prof. R. Grikšienė –

secretary of the Lithuanian Society for Neurosciences.

Assoc. Prof. V. Kisnierienė –

member of the Lithuanian Society for Neurosciences.

Dr. A. Pleskačiauskas –

member of the Lithuanian Society for Neurosciences.

Prof. O. Rukšėnas –

President of the Lithuanian Society for Neurosciences;
Council 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 Laboratorinė medicina (Laboratory Medicine);
European Commission expert;
member of Federation of European Neuroscience Societies (FENS) governing board.

Dr. A. Šoliūnas –

member of the Lithuanian Society for Neurosciences.

DEPARTMENT OF ZOOLOGY

7 Saulėtekio av., LT-10257 Vilnius

Tel. 239 8264, fax 239 8204
E-mail: .

Head – Prof. Habil. Dr. Rimantas Rakauskas

STAFF

Professors: Dr. S. Podėnas, Habil. Dr. R. Rakauskas, Dr. K. Arbačiauskas (part-time).
Asociate professors: Dr. E. Budrys (part-time), Dr. E. Bukelskis, Dr. J. Turčinavičienė, Dr.V. Podėnienė, Dr. R. Bernotienė (part-time), Dr. V. Rakauskas (part-time), Dr. A. Kaupinis (part-time), Dr. G. Skujienė, Dr. A. Petrašiūnas.
Lecturers: Dr. M. Biteniekytė, Dr. R. Aukštikalnienė, S. Skuja (part-time), E. Tijušas (part-time).
Researcher: Dr. J. Havelka.
Doctoral students: J. Danilov, M. Adomaitis, A. Kamarauskaitė.

RESEARCH INTERESTS

Ecosystems and global change
Mapping and catalogization of the Lithuanian 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 and Ecology. Prof. Habil. Dr. R. Rakauskas. 2012–2017.

Distribution, host specificity and molecular diversity studies of an exotic to Central Europe aphid species Brachycaudus divaricatae Shaposhnikov, 1956 accomplished. Biosystematic studies of aphids inhabiting coniferous trees in Lithuania and Central Europe started. Analysis of the biodiversity of spiders and dipterous insects of Lithuania continued. Distributional analysis of the invasive slug species Arion lusitanicus (Mollusca, Pulmonata, Arionidae) in Lithuania started. Monitoring of fish communities in Lithuanian lakes was continued. Programs for fish introductions into Lithuanian lakes were prepared. Specimens of different Diptera (Ephydridae, Keroplatidae, Syrphidae and others) and Coleoptera were identified, adding 3 species new to the Lithuanian fauna. Monitoring of black storks, birds of prey and owls in forests of eastern and southern Lithuania continued. Winter gnats (Trichoceridae), collected in 2016–2017 in Bulgaria, Romania, Russia, Serbia, Norway, were identified, one species new to science was described.

National Research Projects

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

International Projects

EU SYNTHESYS programme, project: HU-TAF-4804: Winter Gnat (Diptera: Trichoceridae) and Crane-fly (Diptera: Limoniidae) Fauna of East Palaeartic and Oriental Regions. Assoc. Prof. Dr. A. Petrašiūnas.

A review of winter gnat (Trichoceridae) fauna of Korea was finalized, one species new to science described.

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)
Zoological Museum, University of Copenhagen (Denmark)
National History Museum, London (UK)
Institute of Zoology, Saint Petersburg (Russia)

OTHER SCIENTIFIC ACTIVITIES

Assoc. Prof. E. Bukelskis –

member of the National Council for the Fishing Management.

Prof. S. Podėnas –

assoc. researcher of the Academy of Natural Sciences, Philadelphia, PA (USA);
expert of the National Centre for Quality Assessment in Higher Education (Lithuania).

Prof. R. Rakauskas –

editorial board member of the journal Aphids and Other Hemipterous Insects;
expert of the National Centre for Quality Assessment in Higher Education;
expert of the Research Council of Lithuania.
member of the Lithuanian Entomological Sodiety.

Assoc. Prof. J. Turčinavičienė –

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 Sodiety.

Assoc. Prof. R. Aukštikalnienė –

member of the Lithuanian Morphological Society.

Dr. G. Skujienė –

curator of the Museum of Zoology of Vilnius University;
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.

Dr. A. Petrašiūnas –

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.

Dr. M. Biteniekytė –

member of the Lithuanian Entomological Sodiety.

CENTRE FOR ECOLOGY AND ENVIROMENTAL RESEARCH

7 Saulėtekio av., LT-10257 Vilnius
Tel. 239 8299
E-mail:

Head – Prof. Dr. Alius Ulevičius

STAFF

Professor: Dr. A. Ulevičius.
Associate professors: Dr. G. Ignatavičius, Dr. J. Satkūnas (part-time), Dr. V. Oškinis.
Assistents: Dr. V. Kalcienė, Dr. I. Nedveckytė, Dr. A. Samas.
Lecturers: G.Trakimas, V. Valskys (part-time).
Doctoral student: V. Valskys.

RESEARCH INTERESTS

Pollution of natural components and anthropogenical 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 2017

Projects Supported by University Budget

Research of Complex Anthropogenic and Biogenic Impact on the Structures and Development of Ecosystems. Dr. A. Ulevičius, Dr. G. Ignatavičius.

Pollution of bottom sediments by heavy metals in water bodies and sapropel quality was assessed in lakes of Lithuania. Seasonal fluctuations of heavy metal concentrations in the Neris river bottom sediments.
Ecotoxicity estimation of surface water sewage with standard bioassay test-Aliivibrio fischeri.
Geomorphological and biocenotical impacts of Eurasian beaver Castor fiber.
Ecological traits and geographical distribution of European Amphibia through Holocene using structural modelling.
Chemoreception of Plodia interpunctella on substrates infected and not infected by micromycetes. 3-methyl-1-butanol is supposed to be the main biomarker.

Main publications:

Ignatavičius, G., Valskys, V., Bulskaya, I., Paliulis, D., Zigmontienė, A., Satkūnas, J. 2017. Heavy metals contamination in surface runoff sediments of urban area of Vilnius, Lithuania. Estonian Journal of Earth Sciences, vol. 66(01), p. 13–20.

Ignatavičius, G., Toleikienė, M. 2017. Optimisation of the conservation of rare and vulnerable plant species in the perspective of climate change in Lithuanian nature reserves. Archives of Environmental Protection, vol. 43(3), p. 61–73.

Krams, I.A., Krama, T., Trakimas, G., Kaasik, A., Rantala, M. J., Škute, A. 2017. Reproduction is costly in an infected aquatic insect. Ethology Ecology & Evolution, vol. 29(1), p. 74–84.

Krams, I. A., Kecko, S., Jõers, P., Trakimas, G., Elferts, D., Krams, R., Luoto, S., Rantala, M. J., Inashkina, I., Gudrā, D., Fridmanis, D., Contreras-Garduño, J., Grantiņa-Ieviņa, L., Krama, T. 2017. Microbiome symbionts and diet diversity incur costs on the immune system of insect larvae. Journal of Experimental Biology, vol. 220(22), p. 4204–4212.

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. Kalcienė. 2017–2020 .

International Research Projects

INTERREG Baltic Sea Region Project: Water management in Baltic forests (WAMBAF). Dr. A. Ulevičius. 2016–2018.

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

Nature Research Centre (Lithuania)
Center For Physical Sciences And Technology (Lithuania)
Vilnius Gediminas Technical University (Lithuania)
University of Latvia (Latvia)
Lithuanian Geological Survey (Lithuania)