Institute of Biotechnology

Sukurta: 15 September 2013

bti8 V. A. Graičiūno, LT 02241 Vilnius
Tel. 260 2103
Fax 260 2116
E-mail:
www.ibt.lt

Director - Prof. Habil. Dr.  Kęstutis Sasnauskas

STAFF

102 research fellows (54 holding research degree), 44 doctoral students.

RESEARCH AREAS

Structural Biology and Bioinformatics
Proteins and Chemical Compounds for Biomedicine

DOCTORAL DISSERTATIONS MAINTAINED IN 2014

D. Kazlauskas. Computational analysis of DNA replication proteins in double-stranded DNA viruses.

DEPARTMENT OF PROTEIN-NUCLEIC ACIDS INTERACTIONS

8 V. A. Graičiūno, LT 02241 Vilnius
Tel. 260 2108, fax 2602116
E-mail:

Head - Prof. Dr. Virginijus Šikšnys

STAFF

Chief research fellows: Prof. Dr. V. Šikšnys, Dr. S. Gražulis, Dr. G. Sasnauskas.
Senior research fellows: Dr. G. Tamulaitienė, Dr. E. Manakova,  Dr. G. Tamulaitis, Dr. M. Zaremba, Dr. G. Gasiūnas.
Research fellow: Dr. A. Šilanskas.
Junior research fellows: Dr. D. Golovenko, T. Šinkūnas, G. Kostiuk.
Post doctoral student: Dr. L. Jakutytė-Giraitienė.
Other researchers: Dr. D. Golovenko.
Doctoral students: T. Karvelis, M. Ukanis, P. Toliušis, E. Zagorskaitė, I. Songailienė, A. Merkys, A. Smirnov.

RESEARCH INTERESTS

Structural and molecular mechanisms of restriction enzymes
Bacterial antivirus defence systems

RESEARCH PROJECTS CARRIED OUT IN 2014

Projects Supported by University Budget

Studies on Structure and Function Relationship of Enzymes and their Complexes. Prof. Dr. V. Šikšnys. 2013–2014.

Many type II restriction endonucleases require binding of two copies of a recognition site for efficient DNA cleavage. Simultaneous interaction of the enzyme with two DNA sites results in DNA loop formation. Using Ecl18kI restriction enzyme as a model system we demonstrate by the single molecule FRET technique that DNA looping is a dynamic process where a DNA loop is repeatedly formed and disrupted.
This study has been performed in collaboration with Dr. Rutkauskas’ team at the Centre for Physical Sciences and Technology. The work in Siksnys’ lab has been supported by Vilnius University budget.

Main publications:

Rutkauskas, D., Petkelyte, M., Naujalis, P., Sasnauskas, G., Tamulaitis, G., Zaremba, M., Siksnys, V. 2014. Restriction Enzyme Ecl18kI-Induced DNA Looping Dynamics by Single-Molecule FRET. J Phys Chem B, vol. 118(29), 8575–82.

National Research Projects

Research Council of Lithuania. The Role of Cas1 ir Cas2 Proteins In Adaptation Mechanism Of CRISPR-Cas systems. (No. MIP 027/2014). 2014–2016. Dr. G. Gasiūnas.

Recently identified adaptive prokaryotic immune system CRISPR-Cas provides acquired immunity against viruses and plasmids. The mechanism of these systems is divided into 2 stages: adaptation and interference. Recent studies have uncovered molecular details underlying the interference step, however the mechanism of the adaptation stage remains to be established. In this project we are investigating the properties of Cas1 and Cas2 proteins and its role in the adaptation mechanism.

Research Council of Lithuania. Expansion of the Crystallography Open Database (COD) and Statistical Analysis of Crystal Structures. (No. MIP-25/2013). Dr. S. Gražulis. 2013–2015.

The COD provides information about crystal lattices, atomic coordinates, temperature factors, as well as publication data that permit linking of structural data with described material properties. To date COD contains more that 210 thousand records.
The COD Web interface provides search capabilities to retrieve crystal data using crystallographic and physico-chemical data; it also permits researchers to upload their data automatically, and to deposit into COD published structures, pre-publication data, or submit crystal data as personal communications to COD.
With the implementation of the COD automated data deposition interface, more stringent requirements for data reliability seem to be appropriate.

Research Council of Lithuania. Structure and Function of 5-methyl and 5-hydroxymethylcytosine-directed Restriction Endonucleases. (No. MIP-27/2012). Dr. G. Sasnauskas. 2012–2014.

Modification-dependent restriction endonucleases recognize the epigenetic marks 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in various sequence contexts. They are promising tools for DNA methylation and hydroxymethylation profiling in mammalian DNA. We study the mechanism of modified DNA recognition employed by these enzymes using various biochemical methods and X-ray crystallography.

Research Council of Lithuania. Function of a Molecular Motor in Atypical Restriction-Modification System. (No. MIP-29/2012). Dr. M. Zaremba. 2012–2014.

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 a DNA translocase activity.

Main publications:

Zaremba, M., Toliusis, P., Grigaitis, R., Manakova, E., Silanskas, A., Tamulaitiene, G., Szczelkun, M.D., Siksnys, V. 2014. DNA cleavage by CgII and NgoAVII requires interaction between N- and R-proteins and extensive nucleotide hydrolysis. Nucleic Acids Res., vol. 42(22), 13887–13896.

Tamulaitiene, G., Silanskas, A., Grazulis, S., Zaremba, M., Siksnys, V. 2014. Crystal structure of the R-protein of the multisubunit ATP-dependent restriction endonuclease NgoAVII. Nucleic Acids Res., vol. 42(22), 14022–14030.

Research Council of Lithuania. Investigation of RNA Interference in Bacteria. (No. MIP‑40/2013). Dr. G. Tamulaitis. 2013–2015.

Immunity against viruses and plasmids in bacteria provided by CRISPR-Cas systems is mediated by a ribonucleoprotein effector complex. Type I (Cascade) and II (Cas9) effector complexes target foreign DNA. We discovered that the Csm complex (Type III-A) of Streptococcus thermophilus targets RNA and established a molecular mechanism for RNA degradation. We demonstrated that Csm complex offers a novel programmable tool for RNA degradation or modification.

Main publications:

Tamulaitis, G., Kazlauskiene, M., Manakova, E., Venclovas, Č., Nwokeoji, A.O, Dickman, M.J., Horvath, P., Siksnys, V. 2014. Programmable RNA shredding by the Type III-A CRIPSR-Cas system of Streptococcus thermophilus. Mol Cell, vol. 56(4), 506–17.

Research Council of Lithuania. Structural and Functional Studies of Restriction Enzyme Family. (No. MIP-41/2013). Dr. G. Tamulaitienė. 2013–2015.

This project aims at investigating structural and functional relationships of restriction endonucleases which share CCGG motif within their recognition sites. We determined crystal structure and DNA cleavage mechanism of restriction endonuclease AgeI, which is unique to Type IIP restriction enzymes. We also initiated crystallization and biochemical studies of restriction endonucleases Kpn2I and PfoI.

Research Council of Lithuania. Projects of the European Social Fund under Global Grant Measure. Structure and Molecular Mechanisms of Bacterial Antivirus Defence Systems. (No. VP1-3.1.-ŠMM-07-K-01-100). Prof. Dr. V. Šikšnys. 2011–2015.

Adaptive microbial immune system, named CRISPR (clustered regularly interspaced short palindromic repeats), provides acquired immunity against viruses and plasmids. Recently CRISPR systems came to prominence as genome editing tools that allow to accurately target any DNA sequence in the human genome. An international team of scientists including prof. Siksnys group at the Institute of Biotechnology of Vilnius University used single-molecule DNA supercoiling to analyse the dynamics of R-loop formation and dissociation for both Cascade- and Cas9-based CRISPR-Cas systems.

Main publications:

Gasiunas, G., Sinkunas, T., Siksnys, V. 2014. Molecular mechanisms of CRISPR-mediated microbial immunity. Cell Mol Life Sci., vol. 71(3), 449–65.

Szczelkun,M.D., Tikhomirova,M.S., Sinkunas,T., Gasiunas,G., Karvelis,T., Pschera,P., Siksnys,V., Seidel,R. 2014. Direct observation of R-loop formation by single RNA-guided Cas9 and Cascade effector complexes.Proc Natl Acad Sci USA, vol. 111(27), 9798–803.

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

Thermo Fisher Scientific Baltics (Lithuania)
Bristol University (UK)
Munster University (Germany)
DANISCO (France)

OTHER SCIENTIFIC ACTIVITIES

Prof. Dr. V. Šikšnys –

  • member of the Lithuanian Academy of Sciences.

DEPARTMENT OF BIOLOGICAL DNA MODIFICATION

8 V. A. Graičiūno, LT 02241 Vilnius
Tel. 260 2114, fax 260 2116
E-mail:

Head - Prof. Habil. Dr. Saulius Klimašauskas

STAFF

Chief research fellow: Prof. Habil. Dr. S. Klimašauskas.
Senior research fellows: Dr. R. Rakauskaitė, Dr. G. Vilkaitis, Dr. E. Kriukienė, Dr. Z. Liutkevičiūtė, Dr. V. Masevičius.
Research fellows: Dr. D. Daujotytė, Dr. G. Lukinavičius, Dr. J. Gordevičius.
Junior research fellows: Dr. R. Gerasimaitė, Z. Staševskij, Dr. M. Tomkuvienė, G. Urbanavičiūtė.
Doctoral students: S. Baranauskė, A. Osipenko, St. Butkytė, M. Mickutė, J. Ličytė.

RESEARCH INTERESTS

Nucleic acids modification enzymes
Epigenome profiling
Biosynthesis of selenoproteins

RESEARCH PROJECTS CARRIED OUT IN 2014

Projects Supported by University Budget

Nucleic Acids Modification Enzymes: Structure, Mechanisms of Action and Directed Engineering. Prof. Habil. Dr. S. Klimašauskas. 2011–2015.

Enzymatic methylation of DNA and RNA proceeds via multiple steps including substrate binding, target base flipping, vast conformational rearrangements in the enzyme, covalent activation of the target cytosine and catalytic transfer. We employ biochemical, biophysical and kinetic analyses combined with x-ray crystallography and protein engineering to delineate the elementary steps and use this knowledge to improve catalytic properties of the natural enzymes.

National Research Projects

Research Council of Lithuania. Studies on the Biogenesis Molecular Mechanism of Non Coding RNAs in Plants. (No. MIP-28/2012). Dr. G. Vilkaitis. 2012–2014.

Several classes of non-coding RNAs with different biological activities and specific functions have been already identified in eukaryotes. These small RNAs govern diverse RNA silencing pathways playing an important role in various biological processes. Regardless of intensive studies carried out in different laboratories over the past decade, many aspects of small RNA biogenesis and molecular mechanism of action remains unclear. This project is focused on the molecular mechanism of non-coding interfering RNAs, microRNAs and various siRNAs, biogenesis in plant cells.

Research Council of Lithuania. Genomic Mapping of Covalently Tagged CpG Sites. (No. MIP-45/2013). Dr. E. Kriukienė. 2013–2015.

The best known epigenetic DNA modification is methylation of cytosine residues at the C5 position of CpG sites. With the recent discovery of 5-hydroxymethylcytosine, the epigenetic community is in need of adequate analytic techniques which are able to sensitively map genome-wide localization of various cytosine modifications – unmodified, 5-methylated or 5-hydroxymethylated cytosine. Our project is focused on developing new epigenetic tools for large-scale DNA modification profiling at single base resolution of all individual CpGs across the entire genome. The new approaches combine covalent derivatization of unmethylated or hydroxymethylated CG sites with suitable compounds by treatment with DNA cytosine-5 methyltransferases and subsequent mapping of such sites by next generation sequencing technologies.

Research Council of Lithuania. A Universal Method for Recombinant Synthesis of Selenoproteins. (No. MIP-115/2012). Dr. R. Rakauskaitė. 2012–2014.

Incorporation of selenocyteine (Sec) into proteins is a promising way to achieve valuable engineered protein products. However, artificial incorporation of Sec into proteins still remains technologically complicated process. We are currently developing a new general method permitting the incorporation of a photocaged Sec residue into a desired position of a protein. Our method has a potential to simplify the synthesis of selenoproteins and therefore to expand their biotechnological utilization.

Projects of the European Social Fund under Global Grant Measure. Molecular tools for Epigenomics and Rnomics. (No. VP1-3.1.-ŠMM-07-K-01-105). Prof. Habil. Dr. S. Klimašauskas. 2011–2015.

Functional analysis of biological systems requires visualization of biomolecules in cells and organisms. This project is dedicated to the development of new techniques that permit detection and mapping of modified cytosine nucleotides in mammalian genomes. Our key strategy is based on utilization of newly discovered enzymatic transformations of DNA. Substantial efforts are also devoted to analysis of small non-coding RNAs and for programmable sequence-specific labeling of other cellular RNAs.

Main publications:

Miropolskaya, N., Esyunina, D., Klimašauskas, S., Nikiforov, V., Artsimovitch, I. and Kulbachinskiy, A. 2014. Interplay between the trigger loop and the F loop during RNA polymerase catalysis. Nucleic Acids Res., vol. 42(1), 544–552.

Liutkeviciute, Z., Kriukienė, E., Ličytė, J., Rudytė, M., Urbanavičiūtė, G., Klimašauskas, S. 2014. Direct decarboxylation of 5-carboxylcytosine by DNA C5-methyltransferases. J Am Chem Soc., vol. 136(16), 5884–7.

International Research Projects

National Institutes of Health (NIH), USA. Direct Single Nucleotide Mapping of Genomic CpG Marks. Prof. S. Klimašauskas. 2013–2015.

Over the past decade, epigenetic phenomena claimed a central role in cell regulatory processes and proved important factors for understanding complex human diseases. One of the best understood epigenetic mechanisms is modification of cytosine residues in DNA. This project is dedicated to developing a break-through technique for genome-wide analysis of the modification status of CpG dinucleotides that combines single-base resolution with targeted and economic sequencing of the genome.

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

Centre for Addiction and Mental Health, University of Toronto (Canada)
Institute for Organic Chemistry (Germany)
University of Paul Sabatier (France)
Institute of Molecular Genetics (Russia)
LEBS, Gif-sur-Yvette (France)

OTHER SCIENTIFIC ACTIVITIES

Prof. Habil. Dr. S. Klimašauskas –

  • editorial advisory board member,  Central European Journal of Biology, http://www.versita.com/cejb/editors/;
  • editorial board member,  Proceedings of the Estonian Academy of Sciences, http://www.kirj.ee/13226/;
  • management committee member, COST action CM1303;
  • member of the Lithuanian Academy of Sciences.

DEPARTMENT OF EUKARYOTE GENETIC ENGINEERING

8 V. A. Graičiūno, LT 02241 Vilnius
Tel. 260 2104, fax 260 2116
E-mail:

Head – Assoc. Prof. Dr. Gintautas Žvirblis

STAFF

Chief research fellows: Dr. A. Gedvilaitė, Prof. Habil. Dr. K. Sasnauskas.
Senior research fellows: Dr. E. Mištinienė, Dr. A. Ražanskienė, Dr. R. Slibinskas, Dr. G. Žvirblis, Dr. R. Petraitytė-Burneikienė, Dr. A. Schweighofer , Habil. Dr. I. Meškienė.
Research fellows: Dr. A. Abraitienė, Dr. R. Abraitis, Dr. E. Čiplys,  Dr. V. Kazanavičiūtė.
Junior research fellows: Dr. A. Bulavaitė, Dr. M. Juozapaitis, Dr. D. Žiogienė, Dr. R. Ražanskas, Dr. M. Zaveckas.
Doctoral students: G. Alzbutas, E. Denkovskienė, M. Norkienė, T. Povilaitis, P. L. Tamošiūnas, R. Vorobjovienė, K. Kvederavičiūtė, J. Lazutka, G. Žvirblytė, E. Bakūnaitė, U. Starkevič, R. Zinkevičiūtė.

RESEARCH INTERESTS

Synthesis of recombinant proteins
Molecular tools for diagnostics
Cell signaling regulation in Arabidopsis
Functions of PP2C phosphatases

RESEARCH PROJECTS CARRIED OUT IN 2014

Projects Supported by University Budget

Synthesis of Chimeric and Native Virus Proteins in Yeast and their Application. Dr. G. Žvirblis. 2012–2014.

Synthesis of viral proteins in yeast demonstrated useful application of the research in diagnostics and producing of active recombinant proteins. Parvovirus virus-like particles (PPV) were expressed in yeast and purified. Analysis showed self-assembly of the particles, valuable for detection of PPV-specific antibodies. Expression of a BiP protein in yeast resulted in a secretion of protein into the medium. Ability of yeast to process signal sequence and secrete simplified purification of BiP protein.

Main publications:

Tamošiūnas, P-L., Petraityte-Burneikiene, R., Lasickiene, R., Akatov, A., Kundrotas, G., Sereika, V., Lelešius, R., Žvirbliene, A., Sasnauskas, K. 2014. Generation of recombinant porcine parvovirus virus-like particles in Saccharomyces cerevisiae and development of virus-specific monoclonal antibodies. J Immunol Res, doi:101155/2014/573531.

Gedvilaite, A., Jomantiene, R., Dabrisius, J., Norkiene, M., Davis, RE. 2014. Functional analysis of a lipolytic protein encoded in phytoplasma phage based genomic island. Microbiol Res., vol. 169(5-6), 388–94.

Čiplys, E., Aučynaitė, A., Slibinskas, R. 2014. Generation of human ER chaperone BiP in yeast Saccharomyces cerevisiae. Microb Cell Fact., vol. 13, 22.

National Research Projects

Research Council of Lithuania. Signalling Components in Stem Cells. (No. MIP-003/2014). Dr. A. Schweighofer. 2014–2016.

Plant survival depends on adaptation to environment. Cell signaling via mitogen-activated protein kinases (MAPKs) and protein phosphatases is important to ensue responses enabling plant adaptation to stress. Our study of Arabidopsis thaliana MAPK and phosphatase gene expression during stomata cell development and in response to stress enabled identification of specific MAPKs and PP2C phosphatase gene expression, suggesting their role in development of stomata, which are cells essential in water/gas exchange between plant and environment and thus supporting our ecosystem.

Research Council of Lithuania. Synthesis of Schmallenberg Virus Proteins and Their Application for Diagnostic Means. (No. MIP-44/2013). Prof. Habil. Dr. K. Sasnauskas. 2013–2015.

To develop improved reagents for Schmallenberg virus serology a high-level yeast expression system was employed to produce recombinant SBV nucleocapsid (N) protein. Our study demonstrates that yeast expression system is suitable for high-level production of recombinant nucleocapsid protein and provides the first evidence on the presence of SBV‑positive antibodies in cow serum specimens collected in Lithuania.

Research Council of Lithuania. Expression Analysis of Anthocyanin Biosynthesis Genes in Horticultural Plants. (No. SVE-06/2012). Dr. V. Kazanavičiūtė. 2012–2015.

The aim of the project is to explore anthocyanin biosynthesis pathways and their regulation in Fragaria, Prunus and Ribes plants. Functional positive regulators of anthocyanin biosynthesis pathway were identified in sweet cherry. It was shown that expression profile of Prunus and Ribes genes involved in anthocyanin biosynthesis pathway is species and variety-specific and strongly depends on the berry ripening stage.

Research Council of Lithuania. Interspecific Hybrids Of Orchard Plant - a Novel Source of Anthocyanins. (No. HIB-2011-03). Dr. Ražanskas. 2011–2014.

The main purpose of this project was to investigate anthocyanin biosynthesis pathway and its regulation in plants belonging to Ribes and Prunus genera and to detect genetic alterations leading to varying levels of anthocyanin synthesis. Full or partial gene sequences encoding transcriptional regulators and enzymes of the flavonoid pathway from several Ribes species and several cultivars of sweet cherry were cloned and sequenced, and their expression during fruit maturation evaluated.

Research Council of Lithuania. Projects of the European Social Fund under Global Grant Measure. The Use of Genome-Wide Analysis for Engineering of New Yeast Strains with Improved Heterologous Expression. (No. VP1-3.1-ŠMM-07-K-02-038). Dr. R. Slibinskas. 2012–2015.

The project aimed at generating new yeast Saccharomyces cerevisiae strains capable of efficient expression of heterologous proteins, by using genome-scale analysis. First, we identified genes implicated in successful protein production experiments by analysis of whole genome or proteome. Then the expression of these genes was increased or suppressed by using genetic engineering methods with subsequent selection of strains with improved measles hemagglutinin translocation and invertase secretion.

NATIONAL INTEGRATED PROGRAMME

Biotechnology and Biopharmacy: Fundamental and Applied Research. (No. VP1-3.1-ŠMM-08-K-01-005). Prof. Habil Dr. K. Sasnauskas. 2012–2015.

The project consists of four different topics. The results obtained for each of these topics are as follows: 1) synthesis of prokaryotic and eukaryotic DNA methylases M.HpaII, M.SssI, M.MpeI, DNMT3A, DNMT3B was investigated in yeast;  2) monoclonal antibodies against surface proteins VP1 of human polyomaviruses KIPyV, WUPyV, PyV6 and PyV7 were generated; 3) a comparison was made of death pathways in the primary and cancer cells after mTHPC induced photodynamic effect; 4) optimization of synthesis of recombinant glycerophosphate oxidase expression in Escherichia coli has been carried out.

JOINT RESEARCH PROGRAMME

Development of New Generation Means for Virus Diagnostics and Prophylaxis and Application in Veterinary Medicine. Dr. A. Gedvilaitė. 2013–2015.

Porcine circovirus type 2 (PCV2)-associated diseases are considered to be a big problem for the worldwide swine industry. The aim of the project is to develop new generation tools for PCV2 diagnostics and prophylaxis. As project advanced the genomes of PCV2b type virus spread in Lithuania were determined and virus capside protein formed particles (Cap VLPs) produced in yeast were used for the generation of PCV2-specific MAbs, vaccination of pigs and development of new sensitive and specific diagnostic test - indirect IgG PCV2 Cap VLP-based ELISA.

Main publications:

Nainys, J., Lasickiene, R., Petraityte-Burneikiene, R., Dabrisius, J., Lelesius, R., Sereika, V., Zvirbliene, A., Sasnauskas, K., Gedvilaite, A. 2014. Generation in yeast of recombinant virus-like particles of porcine circovirus type 2 capsid protein and their use for a serologic assay and development of monoclonal antibodies. BMC Biotechnol., vol. 14, 100.

International Research Projects

SWISS-LT. Signaling Control of Pathogen Induced Plant Immunity. (CH-3-SMM-01/10). Dr. I. Meškienė. 2013–2016.

Signaling control of pathogen induced plant immunity, which is funded by Lithuanian-Swiss cooperation programme to reduce economic and social disparities within the enlarged European Union, under project agreement No CH-3-ŠMM-01/10, implemented by Vilnius University and Fribourg University aims to extend the knowledge on plant cell signaling pathways in responses to pathogens. Towards this aim the specific functions of protein phosphatases acting in signaling pathways induced by plant pathogens have been studied by application of molecular biology, biochemistry and cell biology.

Contractual Research

Recombinant Viral Proteins. Abcam Ltd, London, UK. Dr. G. Žvirblis.

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

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)

OTHER SCIENTIFIC ACTIVITIES

Habil. Dr. I. Meškienė –

  • editorial board member of the Frontiers; 
  • editorial board member of the Frontiers in Technical Advances in Plant Science;
  • reviewer of the BioMed Central; The Plant Journal; The Plant Cell; PLoS One.

MICRO TECHNOLOGIES SECTOR

8 V. A. Graičiūno, LT 02241 Vilnius
Tel. 260 2888, fax 2602116
E-mail:

Head – Dr. Linas Mažutis

STAFF

Chief research fellow: Prof. A. Janulaitis.
Post doctoral student: Dr. R. Vasiliauskas.
Doctoral students: J. Rutkauskaitė, R. Galinis, V. Kiseliovas, V. Milkus, R. Žilionis.

RESEARCH INTERESTS

Microfluidic systems
Microfluidic chips
Directed evolution of computer designed enzymes

RESEARCH PROJECTS CARRIED OUT IN 2014

Research Council of Lithuania. High-Throughput Screening of Antibody-Secreting Cells Using Droplet-Based Microfluidics. (MIP 048/2012). Dr. L. Mažutis. 2012–2014.

We have developed a droplet-based microfluidics for high-throughput analysis and sorting of single cells. Compartmentalization of single cells in microfluidic droplets allows the analysis of secreted proteins, thereby overcoming one of the major limitations of traditional flow cytometry and fluorescence-activated cell sorting (FACS) systems. By using sandwitch ELISA assay we detect antibodies secreted from single mouse hybridoma cells compartmentalized inside 50 pl droplets after only 15 minutes of incubation. Binding assay of secreted antibodies is perform by co-compartmentalizing beads coated with anti-mouse IgG antibodies and a fluorescently-labeled probe: when secreted antibody binds to a probe the fluorescence becomes localized on a bead surface, generating clearly distinguishable signal. Droplets are sorted based on fluorescence intensity of a bead, enriching antibody secreting cells. The microfluidic system described is easily adapted to screen other intracellular, cell-surface or secreted proteins and to screen for catalytic or regulatory activities.

International Research Projects

SWISS-LT. Directed Evolution of Computer Designed Enzymes Using Droplet-Based Microfluidics. (No. CH-3-SMM-01/03). Dr. L. Mažutis. 2012–2016.

All evolutionary systems, whether in nature or in the laboratory, share a common principle: they require a link between genotype (a nucleic acid that can be replicated) and phenotype (a functional trait such as binding or catalytic activity). In nature, such a link is achieved via compartmentalization of genes within living cells. In the laboratory, various biochemical means can be exploited but most of the assays have limited throughput and is challenging to maintain a link between a gene and the diffusive reaction products of enzymatic activity. Furthermore, since selections must be performed for each target individually, large numbers of targets impose serious technical limitations. In this project we are developing a microfluidic system for completely in vitro directed evolution of proteins. By compartmentalizing genes and all components necessary for their in vitro expression we are creating a population of artificial cells  that can be selected at conditions incompatible with living systems.

FP7. Integrated Microfluidic System for Long Term Cell Cultivation, Monitoring and Analysis. BioCellChip. Dr. L. Mažutis. 2012–2015.

The aim of the project is to develop a microfluidic human platelet bioreactor that recapitulates bone marrow stiffness, extracellular matrix composition, micro-channel size, hemodynamic vascular shear stress, and endothelial cell contacts, and it supports high-resolution live-cell microscopy and quantification of platelet production. Physiological shear stresses triggered proplatelet initiation, reproduced ex vivo bone marrow proplatelet production, and generated functional platelets. Modeling human bone marrow composition and hemodynamics in vitro obviates risks associated with platelet procurement and storage to help meet growing transfusion needs.

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

School of Engineering and Applied Sciences, Harvard University (USA)
Centre National de la Recherche Scientifique (France)
HabSel Inc (USA)

DEPARTMENT OF IMMUNOLOGY AND CELL BIOLOGY

8 V. A. Graičiūno, LT 02241 Vilnius
Tel. 260 2117, fax 2602116
E-mail:

Head – Dr. Aurelija Žvirblienė

STAFF

Chief research fellow: Dr. A. Žvirblienė.
Senior research fellows: Dr. A. Kanopka, Dr. J. Matulienė, Dr. M. Plečkaitytė, Dr. P. Stakėnas.
Research fellow: Dr. I. Kučinskaitė-Kodzė.
Junior research fellows: E. Jakubauskienė, R. Lasickienė.
Doctoral students: V. Simanavičienė, D. Dekaminavičiūtė, I. Dalgėdienė, L. Vilys, M. Janulaitienė, M. Zilnytė.

RESEARCH INTERESTS

Monoclonal and recombinant antibodies
Molecular epidemiology of Mycobacterium tuberculosis
Alternative splicing

Projects Supported by University Budget

Development of Monoclonal and Recombinant Antibodies. Dr. A. Žvirblienė. 2011–2015.

The project aims at developing novel antibodies with diagnostic potential. A panel of new monoclonal antibodies against yeast-expressed N protein of human parainfluenza virus type 2 (hPIV2) has been developed. The reactivities of the antibodies with recombinant N proteins of hPIV1 and hPIV3 have been investigated. The antibodies are specific exclusively to hPIV2. In collaboration with company ArcDia (Finland), their potential for a direct detection of hPIV2 in clinical samples will be investigated.

Research on Molecular Epidemiology of Mycobacterium tuberculosis. Dr. P. Stakėnas. 2011–2015.

Incidence of multidrug-resistant tuberculosis in Lithuania is one of the highest in the world. The aims of the project are to characterize population of M. tuberculosis complex bacteria by the means of molecular epidemiology and to clarify the genetic determinants of drug resistance. In 2014 we focussed on sub-typing of the Beijing genotype strains by using additional hypervariable MIRU-VNTR locus aiming to improve a discrimination power of genotyping and continued a search for the novel targets involved in drug resistance.

Main publications:

De Beer, J.L., Ködmön, C., van der Werf, M.J., van Ingen, J., van Soolingen, D; ECDC MDR-TB Molecular Surveillance Project Participants (incl. Stakenas P.). Molecular surveillance of multi- and extensively drug-resistant tuberculosis transmission in the European Union from 2003 to 2011. Euro Surveill. 2014, 19(11):pii=20742.

de Beer, J.L., Ködmön, C., van Ingen, J., Supply, P., van Soolingen, D.; Global Network for Molecular Surveillance of Tuberculosis 2010 (incl. Stakenas P.). Second worldwide proficiency study on variable number of tandem repeats typing of Mycobacterium tuberculosis complex Int J Tuberc Lung Dis. 2014, 18(5):594–600.

Influence of Proteins Interaction with Splicing Factor U2AF for Pre-Mrna Splicing Regulation. Dr. A. Kanopka. 2013–2014.

Regulated splicing is carried out by a protein-ribonucleic acid complex called spliceosome. It is also maintained by splicing factors, one of the most important being U2AF, which is required for the binding of U2 snRNP the pre-mRNA.
This study explores expression of UAP56 (“56 kDa U2AF associated protein”) and its significance to gene expression and regulation in various human cell lines.

National Research Projects

Research Council of Lithuania. Development of Recombinant Antibodies Against Carbonic Anhydrase. (No. MIP-37/2012). Dr. A. Žvirblienė. 2012–2014.

The project aims at developing novel recombinant antibodies with potential antitumor activity. The selected target is human carbonic anhydrase XII (CA XII). Inhibitory antibody 14D6 against CA XII has been developed and characterized. The segments of cDNA encoding immunoglobulin VL and VH regions were cloned from hybridoma cells and inserted into expression plasmids to develop recombinant single-chain antibodies (scFv) in E. coli cells and Fc-engineered scFv in mammalian cells.

Main publications:

Dekaminaviciute, D., Lasickiene, R., Parkkila, S., Jogaite, V., Matuliene, J., Matulis, D., Zvirbliene, A. 2014. Development and Characterization of New Monoclonal Antibodies against Human Recombinant CA XI. Biomed Res Int., 2014:309307.

Dekaminaviciute, D., Kairys, V., Zilnyte, M., Petrikaite, V., Jogaite, V., Matuliene, J., Gudleviciene, Z., Vullo, D., Supuran, C.T., Zvirbliene, A. 2014. Monoclonal antibodies raised against 167-180 aa sequence of human carbonic anhydrase XII inhibit its enzymatic activity. J Enzyme Inhib Med Chem., vol. 29(6), 804–10.

Research Council of Lithuania. Studies on the Mechanism of the Cytolytic Activity of the Bacterial Toxin Vaginolysin. (No. MIP-114/2012). Dr. M. Plečkaitytė. 2012–2014.

Gardnerella vaginalis produces cytolysin vaginolysin which has been suggested to be a contributor to bacterial vaginosis pathogenesis. VLY has been attributed to a group of cholesterol-dependent cytolysins  whose pore-forming activity depends on human CD59. We show that VLY may induce cell lysis following two alternative pathways. One requires only cholesterol and does not depend on hCD59. The second pathway involves hCD59 contribution similarly to ILY. Apparently, under physiological conditions VLY acts in the most effective way by accepting the assistance of hCD59. Our results indicate that VLY represents a distinct group of CDCs whose activity is not restricted to the cells of human origin.

Research Council of Lithuania. Molecular Mechanisms in Alzheimer's Disease. (No. LIG-02/2012). Dr. A. Žvirblienė. 2012–2014.

The project aims at investigatig the effects of beta amyloid (Aβ1-42) and its complexes with specific antibodies on mouse brain primary cell cultures. Monoclonal antibody 11E12 reactive with the N-terminal part of Aβ1-42 has been used for the neurotoxicity studies. It was demonstrated that the oligomeric structure of the antigen is essential for neurotoxic effects. The Fc region of the antibodies bound to oligomers is crucial in causing microglia activation and subsequently death of neurons.

Research Council of Lithuania. Studies on Allergic Diseases Genetic and Environmental Risk Factors in the Lithuanian Newborn Cohort. (No. LIG-04/2012). Dr. A. Žvirblienė. 2012–2014.

The project aims at investigating genetic and environmental factors influencing the risk of allergic diseases in the Lithuanian birth cohort (n=1320). The relationship between certain SNPs and atopy has been studied. Seven selected SNPs - CD14 rs2569190, FLG rs11584340 and rs2184953, FCER1A rs2427837 and rs2251746, IL13 rs20541 and rs1800925 – have been investigated. The study demonstrated different pattern of the association of certain SNPs with allergic sensitization at the age of 2 and 5 years.

Research Council of Lithuania. Splicing Factors and their Regulated miRNA as Cancer Biomarkers for Gastrointestinal System. (No. LIG-10/2012). Dr. A. Kanopka. 2012–2014.

All the cancer-specific alterations of the pre-mRNA splicing within the cell is regulated by expression and activity variations of splicing factors. It has been recently shown that splicing factors also regulate the process of microRNA (miRNA) processing.
The idea of the project is determination of the splicing factor and miRNA expression variations within the cells and tumors. The analysis of such data will enable us to identify and understand the mechanisms for the changes in cancer-associated gene splicing, miRNA expression.

Research Council of Lithuania. Projects of the European Social Fund under Global Grant Measure. Novel Chimeric Proteins with Antiviral Activity. (No. VP1-3.1-ŠMM-07-K-02-039). Dr. A. Žvirblienė. 2012–2015.

The project aims at developing novel recombinant proteins with virus-neutralizing activity and capability to induce virus-specific cellular immune response. Monoclonal and recombinant antibodies against hantavirus Gc glycoprotein and hepatitis B virus surface antigen have been developed and tested for their virus-neutralizing capability. Chimeric virus-like particles with inserted T-cell specific epitopes have been generated and tested for their immunogenicity in a mouse model.

Main publications:

Zvirbliene, A., Kucinskaite-Kodze, I., Razanskiene, A., Petraityte-Burneikiene, R., Klempa, B., Ulrich, R.G., Gedvilaite, A. 2014. The use of chimeric virus-like particles harbouring a segment of hantavirus Gc glycoprotein to generate a broadly-reactive hantavirus-specific monoclonal antibody. Viruses, vol. 6(2), 640–60.

International Research Projects

FP7. Metastatic Tumours Facilitated by Hypoxic Tumour Micro-Environments (METOXIA). Dr. A. Kanopka. 2009–2014.

A striking change in alternative splicing pattern has been observed of genes and alterations in splicing factor expression under pathologic conditions. Hypoxia is a key regulatory factor in tumor growth.
In our studies we have elucidated that hypoxia inducible factor 1 (HIF-1) is indirectly involved in hypoxia dependent pre-mRNA splicing regulation.

Contractual Research

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)
Wurzburg University (Germany) 
Institute for Novel and Emerging Infectious Diseases (Germany)

DEPARTMENT OF BIOTHERMODYNAMICS AND DRUG DESIGN

8 V. A. Graičiūno, LT 02241 Vilnius
Tel. 269 1884, fax 260 2116
E-mail:

Head – Dr. Daumantas Matulis

STAFF

Chief research fellow: Dr. D. Matulis. 
Senior research fellows: Dr. V. Petrauskas, Dr. V. Smirnovas, Dr. A Zubrienė.
Research fellows: Dr. V. Dudutienė, Dr. V. Petrikaitė, Dr. L. Baranauskienė, Dr. E. Čapkauskaitė.
Junior research fellows: Dr. V. Juozapaitienė, J. Jachno, V. Michailovienė, E. Kazlauskas, V. Morkūnaitė.
Doctoral students: D. D. Timm, A. Kasiliauskaitė, V. Pilipuitytė, J. Kazokaitė.

RESEARCH INTERESTS

Function and inhibition of carbonic anhydrases

RESEARCH PROJECTS CARRIED OUT IN 2014

Projects Supported by University Budget

Screening of Active Compounds by Structural Biothermodynamics. Dr. D. Matulis. 2012–2014.

The laboratory rationally designs low molecular weight compounds that specifically and efficiently inhibit target proteins participating in cancer, carbonic anhydrases (CA), chaperones (Hsp90) and epigenetic targets such as histone deacetylases and sirtuins. Over 600 novel inhibitors have been designed, synthesized, and their target-binding measured by TSA, PSA, ITC and enzymatic inhibition. Over 50 ligand-protein structures were determined by X-ray crystallography [1-3].

Main publications:

Christodoulou, M. S., Thomas, A., Poulain, St., Vidakovic, M., Lahtela-Kakkonen, M., Matulis, D., Bertrand, Ph., Bartova, E., Blanquart, Ch., Mikros, E., Fokialakis, N., Passarella, D., Benhida, R., Martinet. 2014. Can we use the epigenetic bioactivity of caloric restriction and phytochemicals to promote healthy ageing? MedChemComm., vol. 5, 1804–18201–17.

Pilipuitytė, V. and Matulis, D. 2014. Intrinsic thermodynamics of trifluoromethanesulfonamide and ethoxzolamide binding to human carbonic anhydrase VII. J Molec Recogn. doi: 10.1002/jmr.2404.

National Research Projects

Research Council of Lithuania. Looking for the Origins of Mammalian Prion 'Strains'. (No. MIP-30/2012). Dr. V. Smirnovas. 2012–2014.

The project is dedicated to studies of recombinant prion protein (PrP) amyloid-like fibrils. We studied elongation of PrP fibrils under a range of different environmental conditions and cross-seeding between different prion strains in vitro. Our main finding suggest a possibility of conformational switching between prion strains may proceed through secondary nucleation mechanism.

Main publications:

Milto, K., Michailova, K., Smirnovas, V. 2014. Elongation of mouse prion protein amyloid-like fibrils: effect of temperature and denaturant concentration. PLoS One, vol. 9(4), e94469.

Research Council of Lithuania. Protein Ligand Binding Volume and its Application in Drug Design. (No. MIP 004/2014). Dr. V. Petrauskas. 2014–2016.

This project is devoted to analyse the thermodynamics of protein volume changes, which are associated with the protein-ligand and protein-protein interactions. The change in the protein volume during the event of ligand binding exhibits a connection with the protein-ligand affinity. The detailed understanding of these thermodynamic variables would stimulate the progress in the rational drug design. The research is conducted with a special attention to the proteins involved in cancer progression and therapy.

Research Council of Lithuania. Carbonic Anhidrase hCA XII as a Potential Marker for Cancer Cells. (No. LIG-09/2012). Dr. D. Matulis. 2012–2014.

Several CAs are key enzymes necessary for the survival and growth of hypoxic tumors, namely, membrane-bound extracellular hCA IX and hCA XII. We have investigated hCA XII as a prognostic marker and developed procedure that could be applied in the diagnosis of various cancers, by visualizing CA XII expression by immunohistochemical methods in cancerous tissues. Clinical samples of cancerous tissues were collected at Vilnius University Institute of Oncology and Tampere University, Finland [1–3].

Main publications:

Morkunaite, V., Baranauskiene, L., Zubriene, A., Kairys, V., Ivanova, J., Trapencieris, P., Matulis, D. 2014. Saccharin Sulfonamides as Inhibitors of Carbonic Anhydrases I, II, VII, XII, and XIII. BioMed Res Int., 2014:638902.

Dudutienė, V., Matulienė, J., Smirnov, A., Timm, D.D., Zubrienė, A., Baranauskienė, L., Morkūnaitė, V., Smirnovienė, J., Michailovienė, V., Juozapaitienė, V., Mickevičiūtė, A., Kazokaitė, J., Bakšytė, S., Kasiliauskaitė, A., Jachno, J., Revuckienė, J., Kišonaitė, M., Pilipuitytė, V., Ivanauskaitė, E., Milinavičiūtė, G., Smirnovas, V., Petrikaitė, V., Kairys, V., Petrauskas, V., Norvaišas, P., Lingė, D., Gibieža, P., Capkauskaitė, E., Zakšauskas, A., Kazlauskas, E., Manakova, E., Gražulis, S., Ladbury, J.E., Matulis, D. 2014. Discovery and characterization of novel selective inhibitors of carbonicanhydrase IX. J Med Chem., vol. 57(22), 9435–9446.

Kišonaitė, M., Zubrienė, A., Čapkauskaitė, E., Smirnov, A., Smirnovienė, J., Kairys, V., Manakova, E., Michailovienė, V., Gražulis, S., Matulis, D. 2014. Intrinsic thermodynamics and structure correlation of benzenesulfonamides with a pyrimidine moiety binding to carbonic anhydrases I, II, VII, XII, and XIII. PLOS One, vol. 9(12), e114106.

Research Council of Lithuania. Projects of the European Social Fund under Global Grant Measure. Design of Selective Carbonic Anhydrase, Hsp90, and Hsp70 Inhibitors and Investigation of their Anticancer Properties. (No. VP1-3.1-ŠMM-07-K-02-009). Dr. D. Matulis. 2012–2015.

The synthesized inhibitor binding energetics are measured by biophysical methods, primarily fluorescent thermal shift assay (FTSA), pressure shift assay (PSA) and isothermal titration Calorimetry (ITC). Target proteins have been produced in large scale by molecular cloning and chromatographic purification. Compound effects on cultured human cancer cell lines are being tested.

Main publications:

Petrikaite, V., Matulis, D. 2014. Inhibitor binding to hsp90: a review of thermodynamic, kinetic, enzymatic, and cellular assays. Curr Protein Pept Sci.,  vol. 15(3), 256–82.

Rutkauskas, K., Zubrienė, A., Tumosienė, I., Kantminienė, K., Kažemėkaitė, M., Smirnov, A., Kazokaitė, J., Morkūnaitė, V., Capkauskaitė, E., Manakova, E., Gražulis, S., Beresnevičius, Z.J., Matulis, D. 2014. 4-Amino-substituted Benzenesulfonamides as Inhibitors of Human Carbonic Anhydrases. Molecules, vol. 19(11), 17356–80.

Morkūnaitė, V., Gylytė, J., Zubrienė, A., Baranauskienė, L., Kišonaitė, M., Michailovienė, V., Juozapaitienė, V., Todd, M.J., Matulis, D. 2014. Intrinsic thermodynamics of sulfonamide inhibitor binding to human carbonic anhydrases I and II. J Enzyme Inhib Med Chem. doi: 10.3109/14756366.2014.908291.

Research Council of Lithuania. Projects of the European Social Fund under Global Grant Measure. (No. VP1-3.1-ŠMM-07-K-02-020). Exploring Flavones As Universal Inhibitors of Amyloid-Like Fibril Formation.  Dr. V. Smirnovas. 2012–2015.

This project is dedicated to studies of flavone derivatives as potential inhibitors of amyloid-like fibrillation. We tested 265 different flavones impact on insulin fibrillation kinetics. We demonstrated that usual ThT fluorescence intensity assay may detect a number of false positives and false negatives, which could be excluded using kinetic curves. We identified 5 very good inhibitors of insulin aggregation, these are going to be tested with other amyloid-forming proteins to find out if universal inhibitor could be identified.

International Research Projects

FP7. Towards Construction of a Comprehensive Map of Amyloid-Ligand Interactions:(-)-Epigallocatechin 3-Gallate and Insulin Amyloid. (EGCG+INSULIN=). Dr. V. Smirrnovas. 2011–2015.

The project is dedicated to the studies of insulin amyloid-like fibril formation and its interaction with epigallocatechin gallate (EGCG). EGCG was reported as an inhibitor of amyloid-like fibril formation in case of many proteins. We found out that stable EGCG does not really affect insulin fibrillation, however, upon oxidation it becomes a very good inhibitor. It also affects fibril elongation, but the effect is much weaker.

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

Institute of Medical Technology, University of Tampere (Finland)
International Institute of Molecular and Cell Biology (Poland)
Lead Generation Biology at Johnson & Johnson Pharmaceutical Research and Development (USA)
Cancer Research Centre, University of Edinburgh (UK)
University of Tubingen (Germany)

OTHER SCIENTIFIC ACTIVITIES

Dr. D. Matulis –

  • editorial board  member of the international journal BMC Biophysics.

APPLIED BIOCATALYSIS SECTOR

Tel. 240 4679, fax 2602116
E-mail:

Head – Dr. Inga Matijošytė

STAFF

Research fellow: Dr. I. Matijošytė.
Junior research fellows: Dr. R. Gruškienė, Dr. B. Pudžiuvytė.
Doctoral students: M. Šulcienė, V. Matikevičienė.

RESEARCH INTERESTS

Biocatalysts and their application

RESEARCH PROJECTS CARRIED OUT IN 2014

Projects Supported by University Budget

Development and Investigation of Novel Biocatalysts and their Respective Processes. Dr. I. Matijošytė. 2013–2014.

The research is directed towards development of biocatalysts with novel activities by three common ways: screening of enzymes, development of biocatalyst and application of biocatalyst. In 2014 the research was focused on construction of metagenomic libraries and their screening for targeted enzyme activities; development of heterologous protein expression systems in yeasts for biocatalyst production; investigation of enzymatic biopolyol synthesis; exploring carrier-free immobilization methods.

Main publications:

Šulcienė, M., Karalius, A., Matijošytė, I. 2014. Chemo-enzymatic route for the production of biopolyol from rapeseed oil. Curr Org Chem, vol. 18(23), 3037–3043.

Kleinaitė, E., Jaška, V., Tvaska, B., Matijosyte, I. 2014. A cleaner approach for biolubricant production using biodiesel as a starting material. J Clean Prod., vol. 75, 40–44.

Contractual research

Identification of Biosamples by 16S RNA Coding DNA Sequences.CC Bioenergy LT, Lithuania, Dr. I. Matijošytė.

Microbiogical Analysis of Biosamples. CC Bioenergy LT, Lithuania, Dr. I. Matijošytė.

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

University of Applied Sciences (Switzerland)
TU Delft (Netherlands)
University of Piza (Italy)

APPLIED BIOCATALYSIS SECTOR

8 V. A. Graičiūno, LT 02241 Vilnius
Tel. 269 1881, fax 2602116
E-mail:

Head - Dr. Česlovas Venclovas

STAFF

Chief research fellow: Dr. Č. Venclovas.
Senior research fellows: Dr. V. Kairys, Dr. M. Margelevičius.
Post doctoral student: Dr. J. Dapkūnas.
Other researchers: Dr. A. Timinskas.
Doctoral students: D. Kazlauskas, V. Raškevičius, K. Timinskas, K. Olechnovič.

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 2014

Projects Supported by University Budget

Computational Studies of Protein Structure, Function And Evolution. Dr. Č. Venclovas. 2014–2016.

In one of the studies together with experimentalists from NorthEastern University (Boston, USA) we explored dynamics of evolutionary related DNA sliding clamps that have different sequences but similar structures. We found that the dynamics of these structurally similar proteins differs significantly indicating that differences in sequence play an important role. In another collaborative study we helped experimentalists from the Institute of Biotechnology to characterize structure and function of Csm complex, which protects bacterial cell from invading foreign nucleic acids.

Main publications:

Tamulaitis, G., Kazlauskiene, M., Manakova, E., Venclovas, Č., Nwokeoji, A.O, Dickman, M.J., Horvath, P. and Siksnys, V. 2014. Programmable RNA shredding by the Type III-A CRIPSR-Cas system of Streptococcus thermophilus. Mol Cell, vol. 56(4), 506–17.

Fang, J., Nevin, P., Kairys, V., Venclovas, C., Engen, J.R., Beuning, P.J. 2014. Conformational Analysis of Processivity Clamps in Solution Demonstrates that Tertiary Structure Does Not Correlate with Protein Dynamics. Structure, vol. 22(4), 572–81.

National Research Projects

Research Council of Lithuania. Bayesian Nonparametrics for Detection of Distant Protein Homology. (No. MIP-49/2013). Dr. M. Margelevičius. 2013–2015.

The project aims at improving the quality of alignments between multiple sequence alignments, or profiles. Modeling profile contexts, fixed-length profile fragments is engaged to achieve this goal. A hierarchical Dirichlet process mixture model is developed to describe the distribution of profile contexts. Even modeling unit-length contexts lead to greater improvement than processing 13-length contexts  previously. A benchmark shows a significant increase in both sensitivity and alignment quality.

Research Council of Lithuania. Projects of the European Social Fund under Global Grant Measure. Making Use of Large-Scale Biological Data for the Development of a New Method to Assess Protein Models and for Studying DNA Replication and Repair Systems in Bacteria and Viruses. (No. VP1-3.1.-ŠMM-07-K-03-004). Dr. Č. Venclovas. 2013–2015.

By making an effective use of large-scale biological data we have been developing a new method for the improved estimation of protein model accuracy and have been trying to achieve a better understanding of DNA replication and repair systems in bacteria and viruses. One of the outcomes in 2014 was a new method for the tessellation of structures of biological macromolecules. In addition, we made a number of discoveries related to the DNA replication proteins of double-stranded DNA viruses.

Main publications:

Olechnovič, K, Venclovas, C. 2014. The CAD-score web server: contact area-based comparison of structures and interfaces of proteins, nucleic acids and their complexes. Nucleic Acids Res., 42(Web Server issue):W259–63.

Olechnovič, K., Venclovas, C., 2014. Voronota: a fast and reliable tool for computing the vertices of the Voronoi diagram of atomic balls. J Comput Chem., vol. 35(8), 672–81.

Kazlauskas, D., Venclovas, C. 2014. Herpesviral helicase-primase subunit UL8 is inactivated B-family polymerase. Bioinformatics, vol. 30(15), 2093–7.

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

Most departments at Vilnius University Institute of Biotechnology (Lithuania)
Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas (Lithuania)
Institute of Molecular and Cell Biology, University of Tartu (Estonia)
Northeasern University, Boston (USA)
University of Cape Town (South Africa)

OTHER SCIENTIFIC ACTIVITIES

Dr. Č. Venclovas –

DEPARTMENT OF BIOINFORMATICS

8 V. A. Graičiūno, LT 02241 Vilnius
Tel. 269 1883, fax 260 2116
E-mail:

Head - Eglė Rudokienė

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

Lithuanian University of Health Sciences (Lithuania)
Nature Research Centre (Lithuania)
Vytautas Magnus University (Lithuania)
Lithuanian Agricultural and Forestry Sciences Centre (Lithuania)