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

67 research fellows (52 holding research degree), 43 doctoral students

RESEARCH AREAS

Structural Biology and Bioinformatics
Proteins and Chemical Compounds for Biomedicine

DOCTORAL DISSERTATIONS MAINTAINED IN 2013

L. Baranauskienė. Analysis of ligand binding to recombinant human carbonic anhydrases I, II, VII, IX and XIII.
M.Tomkuvienė. Methyltransferases as tools for sequence-specific labeling of RNA and DNA.

MAIN CONFERENCES ORGANIZED IN 2013

International conference Epigenetics - Bench to Bedside

MAIN SCIENTIFIC ACHIEVEMENTS IN 2013

The Seventh Framework project Strengthening and Sustaining the European Perspectives of Molecular Biotechnology in Lithuania (MoBiLi) (2009–2013) was accomplished successfully. The MoBiLi project has improved the IBT research capabilities and has helped to increase its research quality and recognition. It contributed to improve the research capacity in biotechnology (human capacity and research infrastructures) of Lithuania.

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. G. Tamulaitis, Dr. M. Zaremba, Dr. E. Manakova, Dr. G. Gasiūnas.
Research fellow : Dr. A Šilanskas.
Junior research fellow : Dr. D. Golovenko.
Post doctoral student: Dr. L. Jakutytė-Giraitienė.
Doctoral students : T. Karvelis, G. Kostiuk, T. Šinkūnas, 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 2013

Projects Supported by University Budget

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

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. Restriction enzymes have now gained widespread application as indispensable tools for the in vitro DNA manipulation. 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.

National Research Projects

Research Council of Lithuania. Expansion of the Crystallography Open Database (COD) and Statistical Analysis of Crystal Structures. (No. MIP-25/2013) The COD project (abbreviated from the Crystallography Open Database, http://www.crystallography.net/) aims at collecting in a single open access database all organic, inorganic and metal organic structures (except for the structures of biological macromolecules that are available at the PDB. The database was founded by Armel Le Bail, Lachlan Cranswick, Michael Berndt, Luca Lutterotti and Robert M. Downs in February 2003 as a response to Michael Berndt’s letter published in the Structure Determination by Powder Diffractometry (SDPD) mailing list]. Since December 2007 the main database server is maintained and new software is developed in the Vilnius University Institute of Biotechnology by Saulius Gražulis and Andrius Merkys, and has now over 200 thousand records describing structures published in major crystallographic and chemical peer-reviewed journals.

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.

Modified cytosine variants 5-methylcytosine (5mC) and the recently discovered 5-hydroxymethylcytosine (5hmC) are involved in the epigenetic regulation of gene expression in humans. Restriction endonucleases that recognize 5mC and 5hmC in different DNA sequence contexts are promising tools for DNA methylation and hydroxymethylation profiling in genomic DNA. The aim of our project is biochemical and structural characterization of these 5mC- and 5hmC-specific restriction enzymes.

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

Atypical restriction-modification (RM) systems NgoAVII and CglI, previously assigned as a Type II RM system, are organized of three genes: a methyltransferase, a restriction endonuclease and a DEAD-family helicase/ATPase. Differently from Type II RM systems DNA cleavage by the NgoAVII and CglI endonucleases requires ATP hydrolysis. The major focus of the project is elucidation of the structural organization of the NgoAVII and CglI endonucleases and their unique mechanism for DNA cleavage.

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

In 2007 a new prokaryote defence system CRISPR-Cas was discovered which provides RNA-mediated adaptive immunity against viruses and plasmids in bacteria and archaea. We aim to establish the complex assembly and silencing mechanism of the Type III-A CRISPR-Cas system using Streptococcus thermophilus as a model system. We have sequenced and cloned genes of S. thermophilus Type III-A system, purified ribonucleoprotein complex and initiated biochemical studies.

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

We investigate structural and functional relationships of restriction endonucleases which share CCGG motif within their recognition sites. We determined crystal structures of apo AgeI and AgeI-DNA complex and designed mutations to correlate structure and function. We also determined crystal structure of BsaWI-DNA complex. Biochemical studies of BsaWI and its tetramerization interface mutants guided by the structure, allowed us to suggest a model for BsaWI function.

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.

Bacteriophages are the most abundant organisms in the biosphere. They infect bacteria in order to reproduce and usually kill the host cell when replication is completed. To evade this deadly threat, bacteria evolved multiple defence barriers. The project aims to establish structural and molecular mechanisms of an adaptive microbial immune system, named clustered regularly interspaced short palindromic repeats (CRISPR) that provides acquired immunity against viruses and plasmids.

Main publications:

Sinkunas, T., Gasiunas, G., Waghmare, S.P., Dickman, M.J., Barrangou, R., Horvath, P., Siksnys, V., 2013. In vitro reconstitution of Cascade-mediated CRISPR immunity in Streptococcus thermophilus. EMBO J, 32(3), 385–94.

Karvelis, T., Gasiunas, G., Miksys, A., Barrangou, R., Horvath, P., Siksnys, V., 2013. crRNA and tracrRNA guide Cas9-mediated DNA interference in Streptococcus thermophilus. RNA biology, vol. 10, no. 5, 841–851.

Gasiunas, G., Siksnys, V., 2013. RNA-dependent DNA endonuclease Cas9 of the CRISPR system: Holy Grail of genome editing? Trends Microbiol, 21(11), 562–7.

Karvelis, T., Gasiunas, G., Siksnys, V., 2013. Programmable DNA cleavage in vitro by Cas9. Biochem Soc Trans., 41(6), 1401–6.

International Grants

FP7: Strengthening and Sustaining the European Perspectives of Molecular Biotechnology in Lithuania (MoBiLi). VU Institute of Biotechnology. 2009–2013.

Contractual Research

Studies on in vivo programmable Meganuclease Cas9 functional activity. CJSC Fermentas/Thermo Fisher Scientific. Prof. Dr. V. Šikšnys.

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

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

OTHER SCIENTIFIC ACTIVITIES

Prof. V. Šikšnys –

DEPARTMENT OF BIOLOGICAL DNA MODIFICATION

8 V. A. Graičiūno, LT 02241 Vilnius
Tel. 260 2114, fax 2602116
E-mail:

Head - Prof. Dr. Habil. Saulius Klimašauskas

STAFF

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

RESEARCH INTERESTS

Nucleic acids modification enzymes
Synthesis of selenoproteins

RESEARCH PROJECTS CARRIED OUT IN 2013

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 small interfering 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. We have investigated the interaction between HEN1 methyltransferase and proteins of microRNA microprocessor complex as well as other double-stranded RNA binding proteins. We have performed primary analysis of ERI1 exonuclease activity.

Research Council of Lithuania. Genomic Mapping of Covalently Tagged CpG Sites . (No. MIP-45/2013).

Post-transcriptional covalent modifications of DNA are important epigenetic factors in mammalian development and disease. The best known DNA modification is methylation of cytosine residues at the C5 position which occurs predominantly in the context of CG dinucleotides in all vertebrates including humans. Most analytical techniques used to study cytosine modifications in mammalian DNA are based on the knowledge of two epigenetic states of cytosine in CG sites: unmodified cytosine and 5-methylated cytosine. With the discovery of 5-hydroxymethylcytosine, the epigenetics community is in need of adequate analytic techniques that are able to sensitively map genome-wide localization of various cytosine modifications – unmodified, 5-methylated or 5-hydroxymethylated cytosine. Our project is dedicated to developing new epigenetic tools for analysis of all epigenetic states of cytosine. The new approach combines methyltransferase-directed derivatization of CG dinucleotides and subsequent their analysis 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.

Recent advancements in protein engineering materialized in a number of valuable products for pharmaceutical, industrial, and research applications. A promising way to achieve valuable engineered protein products is targeted incorporation of rare and unnatural amino acids. For instance, selenocysteine provides a selenium atom with unique chemical characteristics (higher nucleophilicity, lower pKa, and lower redox potential) not attainable in common proteins. Despite its technological potential, artificial incorporation of selenocysteine into proteins still remains technologically complicated process. We are currently developing a new general method which will permit the incorporation of a photocaged selenocysteine residue into a desired position of a protein. The new method has a potential to simplify the synthesis of selenoproteins and therefore to expand their biotechnological utilization.

Patent application:

Klimašauskas S., Rakauskaitė R., Masevičius V. Production of selenoproteins. LT2013069 (2013.07.09).

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:

Kriukienė, E., Labrie, V., Khare, T., Urbanavičiūtė, G., Lapinaitė, A., Koncevičius, K., Li, D., Wang, Ti, Pai, S., Ptak, C., Gordevičius, J., Wang, Sun-Chong, Petronis, A., Klimašauskas, S., 2013. DNA unmethylome profiling by covalent capture of CpG sites. Nature communications, vol. 4. no. 2190, 10 p.

Lukinavičius, G., Tomkuvienė, M., Masevičius, V., Klimašauskas, S., 2013. Enhanced chemical stability of AdoMet analogues for improved methyltransferase-directed labeling of DNA. ACS chemical biology, vol. 8, iss. 6, 1134–1139.

Miropolskaya, N., Esyunina, D., Klimašauskas, S., Nikiforov, V., Artsimovitch, I., Kulbachinskiy, A., 2013. Interplay between the trigger loop and the F loop during RNA polymerase catalysis. Nucleic acids research. ePub October 1, 9 p.

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.

FP7: Strengthening and Sustaining the European Perspectives of Molecular Biotechnology in Lithuania (MoBiLi). VU Institute of Biotechnology. 2009–2013.

Contractual research

Analysis of DNA modification using DNA methyltransferases-mediated DNA priming. Thermo Fisher Scientific Baltics. Prof. Habil. Dr. S. Klimašauskas.

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

Centre for Addiction and Mental Health, University of Toronto (Canada)
Institut 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 –

DEPARTMENT OF EUKARYOTE GENETIC ENGINEERING

8 V. A. Graičiūno, LT 02241 Vilnius
Tel. 260 2104, fax 2602116
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. A.Schweighofer , Habil. Dr. I. Meškienė.
Research fellows : Dr. A. Abraitienė, Dr. R. Abraitis, Dr. V. Kazanavičiūtė, Dr. R. Petraitytė-Burneikienė, Dr. H.J.Pesliakas.
Junior research fellows : Dr. A. Bulavaitė, Dr. E. Čiplys, Dr. M. Juozapaitis, 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.

RESEARCH INTERESTS

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

RESEARCH PROJECTS CARRIED OUT IN 2013

Projects Supported by University Budget

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

Major capsid proteinVP1–derived virus-like particles (VLPs) of four polyomaviruses of birds and hamster polyomavirus (HaPyV) were expressed in yeast and used for serological testing of birds and infected hamster serum samples, The chimeric HaPyV VP1-derived VLPs containing LCMV inserts expressed in yeast were used for their ability to induce B and T cell immune response against insert in vivo.

Main publications:

Muñoz, L.J., Ludeña, D., Gedvilaite, A., Zvirbliene, A., Jandrig, B., Voronkova, T., Ulrich, R.G., López, D.E., 2013. Lymphoma outbreak in a GASH:Sal hamster colony. Arch Virol, 158(11), 2255–65.

National Research Projects

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

In November 2011, a new virus of the genus Orthobunyavirus was isolated from diseased cattle in Germany and was provisionally called Schmallenberg virus (SBV). The objective of the project is developing of fast enzyme – immunoassay based methods for new virus. Virus specific immunoglobin IgM and IgG detection systems will be developed on the basis of virus recombinant proteins and corresponding monoclonal antibodies.

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

The project is aiming at elucidating anthocyanin synthesis pathways and their regulation in plants of Fragaria, Prunus and Ribes genera. Genes regulating anthocyanin biosynthesis pathway are analyzed by transient expression in model tobacco plants. The impact of environmental factors such as temperature, light intensity and light spectrum on the expression of anthocyanin biosynthesis markers is being investigated.

Research Council of Lithuania. Interspecific hybrids of orchard plant - a novel source of anthocyanins. (No. HIB-2011-03). Dr. Ražanskas. 2011–2014.

The main purposes of this project are to investigate anthocyanin biosynthesis pathway and its regulation in plants belonging to Ribes and Prunus genera and to spot genetic alterations leading to varying levels of anthocyanin production in various species and their varieties.

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 aims at generating new yeast Saccharomyces cerevisiae strains capable of efficient expression of heterologous proteins, by using genome-scale analysis. First, identification of genes implicated in successful protein production experiments by analysis of whole genome or proteome. At the second stage the expression of these genes are increased or suppressed by using genetic engineering methods with subsequent selection of strains carrying optimal combinations of introduced changes.

NATIONAL INTEGRATED PROGRAMME

Biotechnology and Biopharmacy: fundamental and applied research. (No. VP1-3.1-ŠMM-08-K-01-005). Prof. K. Sasnauskas. 2012–2015.

The project consists of four directions: new genomics, transcriptomics, RNA-omics and molecular diagnostic tools and their application; recombinant proteins for human pathogens diagnostics. The aim of this direction is to create a human polyomavirus diagnostics; molecular processes in eukaryotic cells: the technological and medical aspects. The aim is to create new tools for cell therapy; biocatalysators and processes for development of carbohydrates bioconversion.

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 the biggest 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 PCV2 samples were collected in selected swine farms of Lithuania and genomes were sequenced. Virus capside proteins were generated in yeast and purified as virus like particles which will be used for development of diagnostics tools and vaccination of pigs.

International Research Projects

FP7. Development of Novel Antiviral Drug against Influenza (FLUCURE). Dr. G. Žvirblis.

FLUCURE is targeted to the essential ribonucleoprotein (RNP) complex within influenza virus to inhibit its replication and spread. The research has pointed the RNA polymerase complex as a major determinant of virulence. RNP complex is the core of viral replication consisting of the PB2, PB1, PA subunits and nucleoprotein (NP). The project is dedicated to the discovery of selective and potent small molecule inhibitors of PB1-PA subunit interaction as well as internal NP interaction and reducing viral activity effectively.

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

In response to pathogenic environment plants generate intracellular signals leading to defense responses. We investigate how plant signaling components control plant immunity by elucidating the functions of the protein phosphatases and kinases in disease responses and plant resistance. Results from this research may indicate new markers for plant breeding programs for enhancement of plant immunity.

Main publications:

Fuchs, S., Grill, E., Meskiene, I., Schweighofer, A., 2013. Type 2C protein phosphatases in plants. FEBS J, 280(20), 681–93.

Lee, Y.P., Giorgi, F.M., Lohse, M., Kvederaviciute, K., Klages, S., Usadel, B., Meskiene, I., Reinhardt, R., Hincha, D.K., 2013. Transcriptome sequencing and microarray design for functional genomics in the extremophile Arabidopsis relative Thellungiella salsuginea (Eutrema salsugineum). BMC Genomics, 14(1), 793.

FP7: Strengthening and Sustaining the European Perspectives of Molecular Biotechnology in Lithuania (MoBiLi). VU Institute of Biotechnology. 2009–2013.

Contractual Research

Recombinant viral proteins . Abcam Ltd, London, UK. Dr. G. Žvirblis.

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)

OTHER SCIENTIFIC ACTIVITIES

Habil. Dr. I. Meškienė –

  • editorial board member of the Frontiers, https://www.frontiersin.org;
  • editorial board member of the Frontiers in Technical Advances in Plant Science.

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.
Senior research fellow: Dr. L. Mažutis.
Post doctoral students: Dr. R.Vasiliauskas
Doctoral students : J. Rutkauskaitė, R. Galinis, V. Kiseliovas, V. Milkus.

RESEARCH INTERESTS

Microfluidic systems
Microfluidic chips
Directed evolution of computer designed enzymes

RESEARCH PROJECTS CARRIED OUT IN 2013

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

Using microfluidics technology we have developed a high-throughput system for single-cell analysis and sorting. For that purpose we encapsulate individual cells into 50 pL droplets and sort droplets containing only those cells that secret therapeutic antibodies. Since cells are encapsulated into droplets the secreted antibodies also remain entrapped inside the same vessel, therefore linking the phenotype (antibody binding activity) with genotype (cell). Due to increased local concentration inside droplets the amount of secreted antibodies significantly reduces the time window necessary for the assay. We believe that such microfluidic platform, coupled with sensitive detectors and direct on-line measurements, will be particularly appealing for biotechnology and biomedicine.

Projects Supported by Agency For Science, Innovation And Technology. Development of microfluidics technology for monodisperse vesicles production and improved drug delivery. (No. 31V-40). Dr. L. Mažutis. 2012–2013.

One of our goals is to develop microfluidic chips allowing production of highly monodisperse vesicles hardly possible using classical approaches. These vesicles will allow encapsulation of biologically active molecules, pharmaceuticals and drugs. By carefully choosing the composition of particles we are aiming to increase the life-time of the encapsulated drugs and improve the pharmokinetics of drug release. This work is being supported by Agency for Science, Innovation and Technology.

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.

This direction of our work is dedicated towards creation of better biocatalysts. Following Nature’s principles, where most reactions are compartmentalized within cells, organelles or even smaller subcompartments, man-made droplets can similarly serve as independent microreactors for performing large numbers of biochemical reactions simultaneously. Therefore, we are combining droplet-based microfluidics technology with directed evolution approaches to optimize computationally designed enzymes.

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

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 – Prof. 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 fellows : Dr. I. Kučinskaitė-Kodzė.
Junior research fellows : E. Jakubauskienė, R. Lasickienė.
Doctoral students : V. Simanavičienė, D. Dekaminavičiūtė, I. Dalgėdienė, L. Vilys, M. Janulaitienė.

RESEARCH INTERESTS

Monoclonal and recombinant antibodies
Molecular epidemiology of Mycobacterium tuberculosis

Projects Supported by University Budget

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

Monoclonal and recombinant antibodies are widely used in diagnostics, biopharmacy and research. The current project aims to develop novel antibodies with diagnostic potential. A panel of new monoclonal antibodies against yeast-expressed hamster polyomavirus major capsid protein VP1 protein has been developed. In collaboration with Salamanca University (Spain), the reactivities of the antibodies with virus-infected cells have been investigated. The specificity of monoclonal antibodies has been proven by the immuhistochemistry staining of polyomavirus-induced lymphoma specimens. The antibodies were further used as immunodiagnostic reagents for the investigation of lymphoma outbreak in a GASH:Sal hamster colony.

Antigenic structure of the nucleocapsid proteins of human paramyxoviruses has been studied using previously developed monoclonal antibodies against human parainfluenza type 3, human metapneumovirus and measles nucleocapsid proteins. The immunodominance of C-terminally located B cell epitopes has been demonstrated.

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

Incidence of tuberculosis in Lithuania, particularly multidrug-resistant is one of the highest in the European Community. The aims of this project are to characterize in detail population M. tuberculosis complex bacteria by the means of molecular epidemiology and to clarify the genetic determinants leading to the emergence of drug resistance. During 2013, we continued the search for mutations including novel plausible targets involved in M. tuberculosis resistance to streptomycin

Influence of proteins interaction with splicing factor U2AF for pre-mRNA splicing regulation. Dr. A. Kanopka. 2013–2014.

A vast majority of eukaryotic genes is composed of exonic (coding) and intronic (non-coding) parts. Alternative splicing of one pre-mRNA can form different mature mRNAs.

It was shown that reduced oxygen tension significantly influences cellular gene expression. One of the factors which are involved in pre-mRNA splicing dependent from oxygen tension regulation is splicing factor U2AF. The U2 snRNP auxiliary factor (U2AF) has been characterized as an essential splicing factor required for efficient recruitment of U2 small nuclear ribonucleoprotein to the 3-splice site in a pre-mRNA. U2AF is heteridimeric factor composed from 35 kDa and 65 kDa subunits (encodes U2AF1 and U2AF2 genes respectively). The U2AF65 subunit through its RNA recognition domains binds to the pyrimidine tract of the pre-mRNA, whereas the U2AF35 subunit contacts the 3-splice site AG nucleotides. In our study we are trying to elucidate role with U2AF65 subunit interacting protein UAP56 in oxygen tension dependent pre-mRNA splicing regulation.

National Research Projects

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

The current proposal aims at developing novel recombinant antibodies with potential antitumor activity. The selected target of the antibodies is human carbonic anhydrase XII (CA XII), the transmembrane enzyme that is aberrantly expressed in certain tumor types. Two stable hybridoma cell lines producing high-affinity IgG antibodies against the selected target sequence of CA XII (aa 167-180) were generated (clones 1D8 and 3C8). It was demonstrated that both antibodies are reactive exclusively with CA XII and do not cross-react with CA I, II, VII, XIII and XIV. The antibodies recognize CA XII in tumour tissues as determined by an immunohistochemistry analysis. Both antibodies inhibit CA XII enzymatic activity as determined by a stopped flow CO2 hydration assay. The segments of cDNA encoding immunoglobulin VL and VH regions were cloned from hybridoma cells and inserted into recombinant plasmid for scFv expression in E.coli cells.

Main publications:

Dekaminavičiūtė, D., Kairys, V., Zilnytė, M., Petrikaitė, V., Jogaitė, V., Matulienė, J., Gudlevičienė, Ž., Vullo, D., Supuran, C.T., Žvirblienė, A., 2013. Monoclonal antibodies raised against 167-180 aa sequence of human carbonic anhydrase XII inhibit its enzymatic activity. Journal of Enzyme Inhibition and Medicinal Chemistr.

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.

Several members of the cholesterol-dependent cytolysin family specifically bind to the human form of CD59 rather than cholesterol. We have demonstrated that the presence of human CD59 is not compulsory for the activity of G.vaginalis cytolysin vaginolysin on the bilayers. The membrane-damaging interaction between vaginolysin and artificial tethered bilayer membranes was observed in the absence of the hCD59 receptor. We demonstrated that vaginolysin binds to cholesterol-rich liposomes in the absence of hCD59 and oligomerize to form SDS-resistant oligomers.

Main publications:

Budvytytė, R., Plečkaitytė, M., Žvirblienė, A., Vanderah, D. J., Valinčius, G., 2013. Reconstitution of cholesterol-dependent vaginolysin into tethered phospholipid bilayers: implications for bioanalysis. PLoS ONE, Vol. 8, iss. 12. Art. no. e82536, 13 p.

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

The aim of the study is to determine how the effects of beta amyloid on cells and membranes correlate with the pathological state of Alzheimer’s disease patients. It was shown that complexes of antibodies against beta amyloid and other oligomeric proteins with their specific monoclonal antigens exert neurotoxic effects on rat and mouse brain primary cell cultures and that oligomeric/multimeric structure of antigen is essential for neurotoxicity of complexes. It was determined that Fc region of antibodies is crucial factor causing microglia activation and subsequently death of neurons. Monoclonal antibody 11E12 reacted with peptide representing the N-terminal sequence aa 1-13, which indicates that the N-terminal part of Aβ1-42 oligomers is exposed on the surface of oligomeric particles.

Main publications:

Dalgedienė, I., Lasickienė, R., Budvytytė, R., Valinčius, G., Morkūnienė, R., Borutaitė, V., Žvirblienė, A. 2013. Immunogenic properties of amyloid beta oligomers. Journal of biomedical science, vol. 20, no 10, 7 p.

Morkūnienė, R., Žvirblienė, A., Dalgėdienė, I., Čižas, P., Jankevičiūtė, S., Baliulytė, G., Jokubka, R., Jankunec, M., Valinčius, G., Borutaitė, V., 2013. Antibodies bound to Aβ oligomers potentiate the neurotoxicity of Aβ by activating microglia. Journal of neurochemistry, vol. 126, no 5, 604 –605.

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 aim of the project is to investigate genetic and environmental factors influencing the risk of allergic diseases in the Lithuanian birth cohort (n=1320). Family members of the cohort participants were also included into the study. It was determined that the risk of the the late onset of asthma correlates with increased levels of IgE antibodies against d1 (the main allergen of mite D.pteronyssinus), d202 (allergen of mite D.pteronyssinus) and f1(egg allergen) as well as increased levels of ECP (R2=0,28; p=0,02). The risk of astma development is not associated with hRSV, hMPV, hPIV 1, hPIV 3 and HBoV induced viral respiratory infections (p>0.05) as well as increased ECP levels in blood serum (p>0.05). However, the control and the study groups differ significantly in regard to hPIV 1-4 infections (p=0.03). To investigate genetic markers, a new PGR system for the detection of FCER1A gene SNP rs2251746 genotype was established and optimised. Genetic analysis revealed that the frequency of CD14 gene SNP rs2251746 C/T and C/C genotypes is significantly higher in the study group as compared to the control group (p=0,046).

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.

One of the stages of cancer development is the activation of messenger RNA (mRNA) synthesis of proto-oncogenes from the existing pre-mRNA molecules within the cell by means of alternative splicing. All the cancer-specific alterations of the pre-mRNA splicing within the cell is regulated by expression and actibity variations of splicing splicing factors. It has been recently shown that splicing factors also regulate the process of microRNA (miRNA) processing, thus affecting diversity of miRNAs in the cells.

The idea of the project will allow determination of the splicing factor expression variations within the cells and to better understand the effects of these variations at the pre-mRNA level. Also the analysis of such data will enable us to identify and understand the mechanisms for the changes in cancer-associated gene splicing and 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 current project aims at developing novel recombinant proteins with virus-neutralizing activity and capability to induce virus-specific cellular immune response. In 2013, novel monoclonal antibodies against hantavirus glycoprotein Gc whave been developed. For this purpose, our patented technology based on the use of novel type of immunogens – chimeric virus-like particles (VLPs) with the inserted target Gc sequences – have been employed. The reactivity of the newly developed monoclonal antibodies with hantavirus-infected cells has been demomonstrated. In collaboration with partners from the Institute of Medical Virology, Charité University Hospital (Berlin, Germany), the capacity of the antibodies to neutralize hantavirus infection in culture has been investigated.

International Research projects

FP7: Metastatic Tumours Facilitated by Hypoxic Tumour Micro-Environments (METOXIA). Dr. A. Kanopka. 2009–2013.

The splicing machinery heavily contributes to biological complexity and especially to the ability of cells to adapt in different developmental stages and altered cellular conditions. A striking change in alternative splicing pattern has been observed of genes and alterations in splicing factor expression under pathologic conditions especially in human cancers. Cancer cells are often confronted with a significant reduction in oxygen availability (hypoxia), which is a major reason for changeover of major cellular processes. Hypoxia is a key regulatory factor in tumor growth and induces a transcriptional cascade that promotes an aggressive cancer phenotype. Numerous publications report changes in pre-mRNA alternative splicing in cancers and cells cultivated under hypoxic or hypoxia mimicking conditions.

We are trying to elucidate factors involved in oxygen tension dependent pre-mRNA splicing regulation. Hypoxia dependable alternative splicing studies will not only provides a deeper understanding of the role of such process in hypoxic cells thus and in cancer, and also suggest possible therapeutic approaches.

FP7: Pan-European Network for the Study and Clinical Management of Drug Resistant Tuberculosis (TB PAN-NET). Dr. P. Stakėnas. 2008–2013.

The main objective of the project is to establish an integrated and synergistic network to address the challenge of drug-resistant TB facing the EU. It is attained through the consortium of partners with experience in the conduct and dissemination of the results of research relating to MDR-TB, TB control and epidemiology. In 2013, we continued a search for polymorphisms of M. tuberculosis genome in the well-known hot spot regions and in novel plausible targets involved in resistance to the second-line injectable drugs and ofloxacin.

FP7: Strengthening and Sustaining the European Perspectives of Molecular Biotechnology in Lithuania (MoBiLi). VU Institute of Biotechnology. 2009–2013.

Contractual Research

Development, purification and characterization of Monoclonal Antibodies against new generation of Polymerases. Thermo Fisher Scientific Baltics. Dr. A. Žvirblienė.

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

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

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

Karolinska Institute (Sweden)
Oslo University (Norway)
Wurzburg University (Germany)
Institute of Experimental Morphology, Pathology and Anthropology with Muzeum of the Bulgarian Academy of Sciences (Bulgaria)

DEPARTMENT OF BIOTHERMODYNAMICS AND DRUG DESIGN

8 V. A. Graičiūno, LT 02241 Vilnius
Tel. 269 1884, fax 2602116
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 : J. Jachno, V. Michailovienė, Dr. V. Jogaitė.

Doctoral students : I. Gailiūtė, R. Chaleckis, V. Raškauskas, D. D. Timm, A. Kasiliauskaitė, V. Pilipuitytė.

RESEARCH INTERESTS

Function and inhibition of carbonic anhydrases

RESEARCH PROJECTS CARRIED OUT IN 2013

Projects Supported by University Budget

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

National Research Projects

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. Conventional chemotherapeutic approaches kill all proliferating cancerous and healthy cells while novel rational drug design approaches attempt to attack only the selected target proteins that participate in disease progression. Our laboratory is primarily interested in the function and inhibition of such targets as carbonic anhydrases (CA), and epigenetic targets such as histone deacetylases and sirtuins.

Several novel inhibitors have been designed, synthesized, and their target-binding energetics measured by the thermal shift assay, pressure shift assay, isothermal titration calorimetry, and enzymatic inhibition. Ligand – protein structures determined by X-ray crystallography.

Main publications:

Capkauskaite, E., Zubriene, A., Smirnov, A., Torresan, J., Kisonaite, M., Kazokaite, J., Gylyte, J., Michailoviene, V., Jogaite, V., Manakova, E., Grazulis, S., Tumkevicius, S., Matulis, D., 2013. Benzenesulfonamides with pyrimidine moiety as inhibitors of human carbonic anhydrases I, II, VI, VII, XII, and XIII. Biorg. Med. Chem, 21, 6937–6947.

Petrauskas, V., Gylytė, J., Toleikis, Z., Cimmperman, P., Matulis, D., 2013. Volume of Hsp90 ligand binding and the unfolding phase diagram as a function of pressure and temperature. Eur Biophys J., 42(5), 355–62.

Dudutienė, V., Zubrienė, A., Smirnov, A., Gylytė, J., Timm, D., Manakova, E., Gražulis, S., Matulis, D. 2013. 4-Substituted-2,3,5,6-tetrafluorobenzenesulfonamides as inhibitors of carbonic anhydrases I, II, VII, XII, and XIII. Bioorg Med Chem., 21(7), 2093 –106.

Jogaitė, V., Zubrienė, A., Michailovienė, V., Gylytė, J., Morkūnaitė, V., Matulis, D. 2013. Characterization of human carbonic anhydrase XII stability and inhibitor binding. Bioorg. Med. Chem., 21(6), 1431–6.

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. This year we studied elongation of PrP fibrils under a range of different environmental conditions. The main achievement is measured activation energies of murine PrP fibril elongation via attaching folded and unfolded monomers.

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

Carbonic anhydrases (CA) are Zn-containing enzymes that catalyze the reversible hydration of carbon dioxide to generate bicarbonate anion and a proton. These proteins are known to regulate and participate in a number of physiological and pathological reactions in human body. Several CAs are key enzymes necessary for the survival and growth of hypoxic tumors. Especially prominent anticancer targets appear to be membrane - bound extracellular hCA IX and hCA XII. It was shown in the literature that the silencing of ca9 and ca12 in animal xenograft experiments has reduced tumor growth by 85%.

During this year of the project, we 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.

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 project aims to design, synthesize and evaluate the inhibitors of several target proteins as potential chemotherapeutic anticancer agents. Several target proteins were selected, human carbonic anhydrases (CAs) and human chaperones (Hsp). Novel compounds are designed by molecular modeling and analogy to existing synthetic and natural compounds. The synthesized inhibitor binding and inhibitory potential are measured by biophysical and enzymatic methods. Target proteins already are produced in large scale by molecular cloning and chromatographic purification. Compound effect on cultured human cancer cell lines will be tested. Such novel compounds that may become anticancer drug candidates.

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. This year we tested 260 different flavones impact on insulin fibrillation kinetics. We found out some inhibitors and some enhancers of fibrillation, though the effect was not very strong. The most interesting finding is ability of some flavone derivatives to change final structure of amyloid fibrils.

International Research Projects

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

The project is dedicated to studies insulin amyloid-like fibril formation and its interaction with epigallocatechin gallate (EGCG). This year we were able to demonstrate that insulin amyloid-like fibril elongation may act similar to enzymatic reaction and experimental data can be described by Michaelis-Menten kinetics and EGCG may act as a competitive inhibitor.

Main publications:

Milto, K., Botyriūtė, A., Smirnovas, V., 2013. Amyloid-like fibril elongation follows Michaelis-Menten kinetics. PLoS ONE, vol. 8, iss. 7. Art. no. e68684, 4 p.

FP7: Strengthening and Sustaining the European Perspectives of Molecular Biotechnology in Lithuania (MoBiLi). VU Institute of Biotechnology. 2009–2013.

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)
Centre for Structural Biochemistry (France)
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

8 V. A. Graičiūno, LT 02241 Vilnius
Tel. 240 4679, fax 2602116
E-mail:

Head – Dr. Inga Matijošytė

STAFF

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

RESEARCH INTERESTS

Biocatalyst and their application

RESEARCH PROJECTS CARRIED OUT IN 2013

Projects Supported by University Budget

Development and investigation of novel biocatalysts and their respective processes. Dr. I. Matijošytė. 2013–2014.

The research is based on developing biocatalysts with novel activities by three common ways: screening of enzymes, development of biocatalyst and application of biocatalyst. Enzymatic activities of laccase, lipase and epoxidase were found in created metagenomic libraries. Biocatalytic polyol synthesis from natural raw material such as castor oil was investigated. Several new microorganims from environmental samples with enrichment were isolated. Alcohol oxidase from Pichia pastoris was immobilized by CLEA method.

National Research Projects

Projects supported by Agency For Science, Innovation And Technology. Development of innovative biocatalytic stain remover. Dr. I. Matijošytė. 2011–2013.

The project was performed in collaboration with a company JC NAUJOJI RINGUVA. The main goal of this project was to create a composition of “express” stain remover which is based on the use of enzymes. The main drawback of such cocktails of enzymes is loss of their activities due to the used protease in the mixture, which tends to autodigestion or degradation of other enzymes. The study was directed towards formulating of stabilizing complexes and investigating the correlation between stability and effectiveness.

Projects supported by Agency For Science, Innovation And Technology. Development of Development of innovative biotechnology for oil base lubricant production. Dr. I. Matijošytė. 2011–2013.

The project was performed in collaboration with a company JSC Biocentras with the main goal to develop an own biocatalyst – lipase for the production of oil based lubricant, because the price of commercial lipase effects the whole process significantly. A new bacterial lipase from Serratia sp. was cloned. Bacterial gene was synthesized de novo by GenScript, using OptimumGene ™ codon optimization technology. The new gene was translocated into the original heterologous protein expression system in the yeast Kluyveromyces lactis, based on a strong promoter and signal peptide usage. Cultivation parameters were determined and immobilization of enzyme was performed by CLEA method.

Contractual research

A new formula for windows cleaner . CJSC Chemopolis, Lithuania, Dr. I. Matijošytė.

Technology for hydrolized lignen fractionation . CJSC Lutora, 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)
Centre of Innovative Medicine (Lithuania)
Naujoji Ringuva (Lithuania)

DEPARTMENT OF BIOINFORMATICS

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, Dr. A.Timinskas.
Post doctoral students: Dr. J. Dapkūnas.
Doctoral students : D. Kazlauskas, J. Višinskienė, V. Raškauskas, K. Timinskas, K. Olechnovič.

RESEARCH INTERESTS

Computational studies of protein structure, function and evolution

RESEARCH PROJECTS CARRIED OUT IN 2013

Projects Supported by University Budget

Studies on Protein Structure, Function and Evolution through Computational Methods. Dr. Č. Venclovas. 2011–2013.

One of our major focuses during 2013 was studies of proteins functioning in DNA and RNA metabolism. In particular, we have been studying the relationship between sequence, structure and dynamics of DNA sliding clamp proteins. We have also been involved in a number of collaborative studies on so-called bacterial “immune” systems that protect bacterial cells from foreign DNA.

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 tasks accomplished in 2013 include: A Bayesian nonparametric model to describe protein sequence families was developed and implemented as a computer software package with the accompanying optimization programs. The model was optimized and tested on a diverse subset of protein sequence families. A publication describing the model and a method for distant protein homology search is now being prepared.

Research Council of Lithuania. Application of interatomic contacts for the assessment of three-dimensional RNA structural models. (No. PRO-02/2012). Dr. Č. Venclovas. 2012–2013.

The aim of the project was to test a new idea of how to evaluate the RNA three-dimensional structural models. The idea was to use the agreement between interatomic contact areas of the reference structure and a model. The more similar corresponding contact areas are, the more accurate model is. We were able to show that the new assessment approach has a number of attractive features missing in structure superposition-based methods. A manuscript reporting the results is in preparation.

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.

One of the tasks of this project is to characterize interactions within protein three-dimensional structures. For this we decided to use the Voronoi diagram of balls, a powerful geometric construct. It is very well suited for studies of protein structure as each atom can be considered to be a ball of van der Waals radius. We developed a robust algorithm to construct the dual of the Voronoi diagram of balls and implemented it as an open source computer application.

Main publications:

Gopinath, K., Venclovas, Č., Ioerger, T.R., Sacchettini, J.C., McKinney, J.D., Mizrahi, V., Warner, D.F., 2013. A vitamin B12 transporter in Mycobacterium tuberculosis. Open biology, vol. 3, no. 2. Art. no. 120175.

Olechnovič, K., Kulberkytė, E., Venclovas, C., 2013. CAD-score: a new contact area difference-based function for evaluation of protein structural models. Proteins, 81(1), 149–62.

Timinskas, K., Balvociute, M., Timinskas, A., Venclovas, C., 2013. Comprehensive analysis of DNA polymerase III α subunits and their homologs in bacterial genomes. Nucleic Acids Res., Oct 7. doi: 10.1093/nar/gkt900.

International Research Projects

FP7: Strengthening and Sustaining the European Perspectives of Molecular Biotechnology in Lithuania (MoBiLi). VU Institute of Biotechnology. 2009–2013.

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

North Eastern University (USA)
University of Cape Town (South Africa)
Tel Aviv University (Israel)
Tartu University (Estonia)

DNA SEQUENCING CENTER

8 V. A. Graičiūno, LT 02241 Vilnius
Tel. 269 1883, fax 2602116
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)