ABOUT
The Department has up to 50 years of experience in composing and implementing/managing educational programs as well as providing a learning environment for undergraduate and graduate studies in Biochemistry and Molecular Biology and PhD studies in Biochemistry.
The research field of the Department, in overall approach, is studies of structure, functions and transformations of biomolecules in model and living systems. Our members are experts in molecular and cell biology of eukaryotic and prokaryotic cells, biochemistry of nucleic acids and proteins. Our specific research interests include cell death and its modulation, bacterial stress responses and pathogenesis, applied biosynthesis of nucleic acids, antivirals, membrane biochemistry, DNA-protein interactions, enzymatic catalysis and conversion of biomass. The Department has facilities for cell imaging and functional analysis, experimental research of NA and proteins, chemical analysis of biological compounds.
Head of department:
Assoc.prof., dr. Aušra Sasnauskienė
RESEARCH
Molecular Mechanisms of Bacterial Antibiotic Resistance and Pathogenesis
Principal investigators
Prof. Edita Sužiedėlienė
Dr. Julija Armalytė
Group members
Dr. Danutė Labeikytė
Dr. Arvydas Markuckas
Dr. Kęstutis Sužiedėlis
Ramutė Pagalytė
Phd students
Laurita Klimkaitė
Tomas Liveikis
Research topics
Our research is focused towards understanding the molecular basis underlying the bacterial antibiotic resistance in clinic and in the environment with the emphasis on novel resistance mechanisms and on the bacterial cell features contributing to pathogenesis. Infections caused by the group of gram-negative bacteria that are resistant to nearly all currently available antibiotics is a serious concern in clinical settings worldwide. Bacteria, previously considered as non-pathogenic, due to their ability to acquire multidrug-resistance and virulence traits, are currently becoming the ones of the most important hospital infection agents. The opportunistic pathogen Acinetobacter baumannii causes a variety of difficult-to-treat nosocomial infections to critically ill patients. The characteristic features of A. baumannii are the ability to withstand prolonged periods of dryness, form biofilms on various surfaces including medical equipment, upregulate intrinsic resistance mechanisms and acquire new resistance genes through plasmids, as well as the ability to adhere and colonise the host cells. Another opportunistic pathogen Stentrophomonas maltophilia is receiving increased attention in the clinic due to its innate multidrug-resistance causing difficult-to-treat infections, combined with a lacking knowledge about the molecular mechanisms causing the pathogenicity. Understanding the molecular basis of pathogenesis may bring novel insights into pathogenicity and development of novel antibacterial strategies.
Projects
Science promotion fund of Vilnius University project “Synergistic Antibiotic-Photodynamic Therapy Combination in Inactivation of Opportunistic Pathogen Stenotrophomonas maltophilia”, No. MSF-JM-3/2021. Project participant – L. Klimkaitė (2021-2022).
Programme for the European Union Funds Investments in Lithuania, Funding instrument - European Regional Development Fund, measure 01.2.2-LMT-K-718 „Targeted Research in Smart Specialisation Areas“, project „Analysis of Individualized Upper Respiratory Tract Microbiome – a novel tool for diagnostics and healthcare (YourAirwayMicrobiome)“, No. 01.2.2-LMT-K-718-03-0079. Project leader Innovative Medicine Center, project coordinator for Vilnius University dr. J. Armalytė (2020-2023).
National research program “Healthy ageing”, project “Development of virus-like particles-based vaccine against Acinetobacter baumannii“ (No. S-SEN20-1). Principal ivestigator dr. Julija Armalytė (2020–2021).
National research program “Sustainability of agro, forest and water ecosystems ”, project “The influence of intensive fish farming on aquatic microbiome and resistome“, No. S-SIT-20-6. Researcher dr. Julija Armalytė (2020-2021).
National research program “Sustainability of agro, forest and water ecosystems ” project “Influence of intensive farming on development, persistence and spread of bacteria resistant to antimicrobials and biocides in soil and water”. Project coordinator for Vilnius University dr. J. Armalytė (2015–2018).
Laboratory of Nucleic Acids Biochemistry
Principal investigator
Prof. Saulius Serva
Group members
Dr. Aleksandras Konovalovas
Dr. Algirdas Mikalkėnas
Dr. Lina Aitmanaitė
PhD students
Enrika Celitan
Gerda Skinderytė
Research
Group is actively engaged in research focused on two main directions:
• Molecular mechanisms of innate yeast Saccharomyces viruses;
• Design and investigation of nucleoside- and nucleotide-based antivirals.
The innate viruses of Saccharomyces and closely related yeasts are being investigated to understand the relations with host in order to elucidate the evolutionary pathways and uncover the principles of dsRNA virus distribution within an ecosystem. We use the molecular biology techniques, involving advanced level manipulations on genomic material such as RNA cloning along with reverse genetics approach. Transcriptomic, proteomic and phenomic consequences of dsRNA viruses on the host cell are interpreted as model framework to establish a universal mechanisms behind any virus of interest. Viral capsids are purified and developed for the facilitated delivery of bioactive materials.
Nucleoside/nucleotide based antivirals constitute an essence of the modern high efficacy retroviral treatment. We rest on the fundamental principles of enzyme catalysis to design and develop antiviral compounds. The aim of our research is to develop the drugs active at the level of catalytic cycle of retroviral replication enzymes, linking the exclusive specificity and efficacy into the binding approach. These compounds are also beneficial for elucidation of the molecular mechanisms of reverse transcriptase inhibition.
Methods
The broad range of methods from classic to those recently developed are employed in a lab. We master microbiology, gene and genome engineering, next generation DNA and RNA sequencing (Oxford Nanopore), bioinformatics, enzymology, cell culture and other techniques. The obtained data are integrated by Systems Biology approach so creating a paradigm network for the virus-host interactions.
Projects (since 2017)
Ministry of Education, Science and Sports, Short-term research in health and education project “System for virus spread control and extreme situation management during COVID-19 epidemics”, Nr. S-DNR-20-2 (2021).
European Cooperation in Science and Technology (COST) activity CA17103: “Delivery of antisense RNA therapeutics (DARTER)” (P-COST-20-3). 2020-2022.
Vilnius University Science Advancement Fund Project „Investigation of Totiviridae family virus ScV-LA biogenesis in native environment“, Nr. MSF-JM-7 (2019-2020).
EU Horizon 2020 Research and Innovation Program Project “Sonic Drilling coupled with Automated Mineralogy and chemistry On-Line-On-Mine-Real-Time” (SOLSA) (2016-2020).
Baltisch-Deutsches Hochschulkontor, Project "Life cycle of yeast dsRNA viruses uncovered by advanced fluorescent microscopy" (2019).
Research Council of Lithuania, Project of National Research Program „Sustainability of agro-, forest and water ecosystems”: “Agroecosystems microbiota under climate change: structure and concordance mechanisms", SIT-07/2015 (2015-2018).
Molecular mechanisms of resistance to anticancer treatment
Principal investigator
Dr. Aušra Sasnauskienė
Group members
Dr. Violeta Jonušienė
Dr. Daiva Dabkevičienė
Vilmantė Žitkutė
Eglė Žalytė
Research topics
Research interests of our group:
• Investigation of molecular mechanisms of resistance to anticancer treatment;
• Functional studies of human primary cells.
Investigation of molecular mechanisms of resistance to anticancer treatment
Acquired drug resistance is a major limitation of cancer treatment. Resistance of cancer cells can emerge due to various factors: alterations in drug transport and metabolism, modification of drug targets, activation of DNA repair or changes in cell death induction. Deeper understanding of chemoresistant cell physiology, in particular cell death and survival signalling, suggests new possible targets to overcome cancer cell resistance.
We study molecular mechanisms that determine cancer cell susceptibility to agents of chemotherapy, targeted therapy or immune checkpoint inhibition. Our aim is to identify potential targets for anti-cancer therapy in colorectal and endometrial cancer cells.
In collaboration with researchers from Vilnius University Life Sciences Center Institute of Biochemistry, we investigate the use of nanotubes of bacteriophage origin as potential drug carriers. We evaluate the mechanisms of nanotube entry and transport in cancer cells.
Functional analysis of human primary cells
In collaboration with the Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, we analyze primary cells of patients having rare genetic diseases. We aim to characterize functional changes of primary cells and correlate them with alterations in genome and transcriptome.
Methods
Culturing of cell cultures and primary cells in 2D and 3D systems; immunoenzymatic assays: Western blot, ELISA; quantitative PCR; subcellular localization studies using confocal microscopy; flow cytometry; functional analysis of gene expression using siRNA and CRISPR-Cas techniques.
Projects (since 2017)
Science promotion fund of Vilnius University project “Application of CRISPR-Cas13 technology in studying mechanisms of chemoresistance”, No. MSF-JM-2/2021. Project leader V. Žitkutė (2021-2022).
Research Council of Lithuania National programme “Healthy ageing” project “Self-assembling Phage Proteins for Targeted Nanomedicine”, No. P-SEN-20-4. Participants: A. Sasnauskienė, V. Žitkutė (2020-2021).
Science promotion fund of Vilnius University project “Genome and transcriptome analysis in pathogenesis studies of rare inherited diseases”, No. MSF-JM-2/2020. Participants: A. Sasnauskienė, V. Žitkutė (2020).
Research Council of Lithuania. Project “Redox Chemistry, Biochemistry and Cytotoxicity of Aromatic Nitrocompounds and N-oxides: a New Look”, No. DOTSUT-34/09.33-LMT-K712-01-0058. Participant V. Jonušienė (2018–2021).
Research Council of Lithuania, National programme “Healthy ageing” project “Novel biomarkers for individualized therapy of colon cancer: proteomics, microRNomics and clinics”, No. SEN-17/2015. Participants V. Jonušienė, A. Sasnauskienė (2015-2018).
Molecular mechanisms of intracellular trafficking
Principal investigator
Prof. Vytautė Starkuvienė Erfle
Research topics
Intracellular trafficking distributes newly synthesized and endocytosed material to diverse cellular destinations and, by doing so, ensures cellular homeostasis. Deregulation of cargo trafficking leads to ever-increasing list of diseases such as cancer or cardio-vascular. Intracellular trafficking strongly contributes to cell differentiation and aging processes. Trafficking can be divided into several pathways: secretory mechanisms that transport cargo from the endoplasmic reticulum to the Golgi complex, and from there on – to the plasma membrane, lysosomes or cell outside. Endocytosis is responsible for cellular entry of various ligands, growth factors or viruses. Both, secretory and endocytic pathways are closely related to degradation, autophagy, cell death and division, transcription and translation. Our aim is to analyse how endocytosis machinery respond and adapt to changes in cell outside. The projects are running at Vilnius and Heidelberg (Germany) Universities.
Methods
To dissect the complexity of trafficking pathways, we use cell biology, molecular genetics and biochemistry techniques. The methodological focus in the group lies in high-throughput and high-resolution fluorescence microscopy. We work with cancer and healthy primary cells in 2D and 3D environment; and modify gene, transcript and protein expression and function by gene editing, RNAi, drug and antibody-mediated approaches, respectively. We also develop techniques to perform these experiments with little side effects and on varying biological scales..
Complexity of endocytosis defines the efficiency of cell modification
Cargo intracellular delivery depends on effectiveness of endocytosis, which differs in individual cells. GFP protein enters some cells efficiently and localizes to cytoplasm. In contrast, some cells fail to internalize this cargo. Part of cells trap GFP in their endosomes after internalization.
Courtesy: Dr S. Liechocki, Heidelberg University
MAIN PUBLICATIONS
Molecular Mechanisms of Bacterial Antibiotic Resistance and Pathogenesis:
Klimkaitė L, Armalytė J, Skerniškytė J, Sužiedėlienė E The Toxin-Antitoxin Systems of the Opportunistic Pathogen Stenotrophomonas maltophilia of Environmental and Clinical Origin" 2020 Toxins (Basel) 12(10):E635 10.3390/toxins12100635.
Krasauskas R, Skerniškytė J, Martinkus J, Armalytė J, Sužiedėlienė E Capsule Protects Acinetobacter baumannii From Inter-Bacterial Competition Mediated by CdiA Toxin 2020 Frontiers in Microbiol. 11:1493 10.3389/fmicb.2020.01493
Skerniškytė J; Karazijaitė E; Deschamps J; Krasauskas R; Armalytė J; Briandet R; Sužiedėlienė E Blp1 protein shows virulence-associated features and elicits protective immunity to Acinetobacter baumannii infection 2019 BMC Microbiology 19(1):259 10.1186/s12866-019-1615-3
Krasauskas R, Skerniškytė J, Armalytė J, Sužiedėlienė E. The role of Acinetobacter baumannii response regulator BfmR in pellicle formation and competitiveness via contact-dependent inhibition system 2019 BMC Microbiology 19(1):241. 10.1186/s12866-019-1621-5
Miškinytė M, Juškaitė R, Skerniškytė J, Voldemarienė V, Valuckas KP, Kučinskienė ZA, Sužiedėlis K, Sužiedėlienė E. High incidence of plasmid-mediated quinolone resistance (PMQR) genes among antibiotic-resistant Gram-negative bacteria from patients of the Lithuanian National Cancer Center 2019 Infectious Diseases (London, England), 51(6):471-474. 10.1080/23744235.2019.1591637
Skerniškytė J, Karazijaitė E, Deschamps J, Krasauskas R, Briandet R, Sužiedėlienė E. The Mutation of Conservative Asp268 Residue in the Peptidoglycan-Associated Domain of the OmpA Protein Affects Multiple Acinetobacter baumannii Virulence Characteristics 2019 Molecules, 24(10). pii: E1972. 10.3390/molecules24101972
Armalytė J, Skerniškytė J, Bakienė E, Krasauskas R, Šiugždinienė R, Kareivienė V, Kerzienė S, Klimienė I, Sužiedėlienė E, Ružauskas M. Microbial Diversity and Antimicrobial Resistance Profile in Microbiota From Soils of Conventional and Organic Farming Systems 2019 Frontiers in Microbiology, 10:892 10.3389/fmicb.2019.00892
Skerniškytė J, Krasauskas R, Péchoux C, Kulakauskas S, Armalytė J, Sužiedėlienė E. Surface-Related Features and Virulence Among Acinetobacter baumannii Clinical Isolates Belonging to International Clones I and II 2019 Frontiers in Microbiology, 9:3116 10.3389/fmicb.2018.03116
Laboratory of Nucleic Acids Biochemistry:
Aitmanaitė L, Konovalovas A, Medvedevas P, Servienė E, Serva S. Specificity Determination in Saccharomyces cerevisiae Killer Virus Systems. Microorganisms. 2021 Jan 23;9(2):236.
Ravoitytė B, Lukša J, Yurchenko V, Serva S, Servienė E. Saccharomyces paradoxus Transcriptional Alterations in Cells of Distinct Phenotype and Viral dsRNA Content. Microorganisms. 2020 Nov 30;8(12):E1902.
Vepštaitė-Monstavičė I, Lukša J, Konovalovas A, Ežerskytė D, Stanevičienė R, Strazdaitė-Žielienė Ž, Serva S, Servienė E. Saccharomyces paradoxus K66 Killer System Evidences Expanded Assortment of Helper and Satellite Viruses. Viruses. 2018 Oct 16;10(10). pii: E564.
Lukša J, Vepštaitė-Monstavičė I, Yurchenko V, Serva S, Servienė E. High content analysis of sea buckthorn, black chokeberry, red and white currants microbiota - A pilot study. Food Res Int. 2018 Sep;111:597-606.
Algirdas Mikalkėnas, Bazilė Ravoitytė, Daiva Tauraitė, Elena Servienė, Rolandas Meškys & Saulius Serva (2018) Conjugation of phosphonoacetic acid to nucleobase promotes a mechanism-based inhibition, Journal of Enzyme Inhibition and Medicinal Chemistry, 33:1, 384-389.
Iglė Vepštaitė-Monstavičė, Juliana Lukša, Ramunė Stanevičienė, Živilė Strazdaitė-Žielienė, Vyacheslav Yurchenko, Saulius Serva, Elena Servienė, Distribution of apple and blackcurrant microbiota in Lithuania and the Czech Republic, Microbiological Research, Volume 206, 2018, Pages 1-8.
Grybchuk D, Akopyants NS, Kostygov AY, Konovalovas A, Lye LF, Dobson DE, Zangger H, Fasel N, Butenko A, Frolov AO, Votýpka J, d'Avila-Levy CM, Kulich P, Moravcová J, Plevka P, Rogozin IB, Serva S, Lukeš J, Beverley SM, Yurchenko V. Viral discovery and diversity in trypanosomatid protozoa with a focus on relatives of the human parasite Leishmania. Proc Natl Acad Sci U S A. 2018 Jan 16; 115(3):E506-E515.
Lukša J, Ravoitytė B, Konovalovas A, Aitmanaitė L, Butenko A, Yurchenko V, Serva S, Servienė E. Different Metabolic Pathways Are Involved in Response of Saccharomyces cerevisiae to L-A and M Viruses. Toxins (Basel). 2017 Jul 25;9(8).
Mikalkėnas A, Ravoitytė B, Tauraitė D, Serva S. 2017. Pyridone-based nucleotide analogues accepted for DNA biosynthesis. Biologija. 2017, v. 1, 42-48.
Molecular mechanisms of resistance to anticancer treatment:
Lysosome-targeted photodynamic treatment induces primary keratinocyte differentiation. Daugelaviciene N, Grigaitis P, Gasiule L, Dabkeviciene D, Neniskyte U, Sasnauskiene A. J Photochem Photobiol B. 2021 May;218:112183. doi: 10.1016/j.jphotobiol.2021.112183. Epub 2021 Mar 29. PMID: 33831753
Notch and Endometrial Cancer. Jonusiene V, Sasnauskiene A. Adv Exp Med Biol. 2021;1287:47-57. doi: 10.1007/978-3-030-55031-8_4. PMID: 33034025 Review.
Exogenous interleukin-1α signaling negatively impacts acquired chemoresistance and alters cell adhesion molecule expression pattern in colorectal carcinoma cells HCT116. Grigaitis P, Jonusiene V, Zitkute V, Dapkunas J, Dabkeviciene D, Sasnauskiene A. Cytokine. 2019 Feb; 114:38-46. doi: 10.1016/j.cyto.2018.11.031. Epub 2018 Dec 22. PMID: 30583087
Significance of Notch and Wnt signaling for chemoresistance of colorectal cancer cells HCT116. Kukcinaviciute E, Jonusiene V, Sasnauskiene A, Dabkeviciene D, Eidenaite E, Laurinavicius A. J Cell Biochem. 2018 Jul;119(7):5913-5920. doi: 10.1002/jcb.26783. Epub 2018 Apr 10. PMID: 29637602
Effect of mTHPC-mediated photodynamic therapy on 5-fluorouracil resistant human colorectal cancer cells. Kukcinaviciute E, Sasnauskiene A, Dabkeviciene D, Kirveliene V, Jonusiene V. Photochem Photobiol Sci. 2017 Jul 1;16(7):1063-1070. doi: 10.1039/c7pp00014f. Epub 2017 May 16. PMID: 28509917
Molecular mechanisms of intracellular trafficking:
Kaipa JM, Starkuviene V, Erfle H, Eils R, Gladilin E. Transcriptome profiling reveals Silibinin dose-dependent response network in non-small lung cancer cells. PeerJ. 2020 Dec 16;8:e10373. doi: 10.7717/peerj.10373.
Liu, SJ; Majeed, W; Grigaitis, P; Betts, MJ; Climer, LK; Starkuviene, V; Storrie, B. Epistatic Analysis of the Contribution of Rabs and Kifs to CATCHR Family Dependent Golgi Organization. Front Cell Dev Bio, 2019, Aug 2;7:126. doi: 10.3389/fcell.2019.00126.
Starkuviene, V., Kallenberger, SM., Beil, N., Lisauskas, T., Schumacher, BS., Bulkescher, R., Wajda, P., Gunkel, M., Beneke, J., Erfle, H. (2019) High-Density Cell Arrays for Genome-Scale Phenotypic Screening. SLAS Discov. 2019 Mar;24(3):274-283. doi: 10.1177/2472555218818757.
Bulkescher, R., Starkuviene, V., & Erfle, H. (2017) Solid-phase reverse transfection for intracellular delivery of functionally active proteins. Genome Res. 2017 Oct;27(10):1752-1758. doi: 10.1101/gr.215103.
Gunkel, M., Erfle, H., & Starkuviene, V. (2016). High-Content Analysis of the Golgi Complex by Correlative Screening Microscopy. Methods Mol Biol, 111-121.
DEPARTMENT STAFF
PARTNERS
Molecular Mechanisms of Bacterial Antibiotic Resistance and Pathogenesis:
Prof. Modestas Ružauskas (Lithuanian University of Health Sciences (The prevalence of antibiotic-resistant bacteria in the environment)).
Dr. Irina Buchovec (Vilnius University, Faculty of Physics (The application of light technologies in biomedicine and food safety, inactivation of pathogens using antimicrobial photodynamic therapy)).
Laboratory of Nucleic Acids Biochemistry:
Dr. Elena Servienė (Nature Research Center, Vilnius)
Dr. Dainius Martuzevičius (Kaunas University of Technology)
Dr. Vytautė Starkuvienė-Erfle (BioQuant, Heidelberg University, Heidelberg, Germany)
Dr. Vyacheslav Yurchenko (Life Science Research Centre, University of Ostrava, Czech Republic)
Dr. Martins Katkevics (Latvian Institute of Organic Synthesis, Riga, Latvia)
Dr. Pavel Plevka (CEITEC, Masaryk University, Brno, Czech Republic)
Molecular mechanisms of resistance to anticancer treatment:
Dr. Vida Časaitė (Institute of Biochemistry, Life Sciences Center, Vilnius University)
Dr. Eglė Preikšaitienė (Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University)
Dr. Vytautė Starkuvienė (BioQuant, Heidelberg University, Heidelberg, Germany)
Molecular mechanisms of intracellular trafficking:
Dr. R. Valiokas, FTMC
Prof. Dr. Med. M. Keese, University Mannheim Clinics, Heidelberg University
Prof. S. Serva, Vilnius University
Dr. A. Sasnauskienė, Vilnius University