Group of systems biology

Head

Maria Yu. Obolens'ka

Professor, Dr. Sci. (Mol. Biol.)
.: (380-44) 526-11-39;
: (380-44) 526-07-59;
E-mail: m.obolenska@gmail.com

Education and Degrees:

19581964 Graduate Student, Bogomolets National Medical University, Kyiv, Ukraine

19641967 Postgraduate Student, Department of Molecular Biology, D. F. Chebotarev State Institute of Gerontology, NAMSU, Kyiv, Ukraine

1968 Ph.D. (biochemistry)

1999 Dr.Sci. (molecular biology)

Professional Employment:

19641975 Junior Research Scientist, Department of Molecular Biology, D. F. Chebotarev State Institute of Gerontology, NAMSU, Kyiv, Ukraine

19751980 Research Scientist, Department of Molecular Mechanisms of Protein Biosynthesis, Institute of Molecular Biology and Genetics (IMBG), NASU, Kyiv, Ukraine

19801991 Senior Research Scientist, Department of Molecular Mechanisms of Protein Biosynthesis, IMBG NASU, Kyiv, Ukraine

19911994 Research Scientist, Institute of Molecular and Cell Biology, Albert-Ludwig University, Freiburg i. Br., Germany

19941999 Senior Research Scientist, group leader, Department of Translational Mechanisms of Genetic Information (DTMGI), Laboratory of Protein Biosynthesis, IMBG NASU, Kyiv, Ukraine

20002009 Leading Research Scientist, DTMGI, Laboratory of Protein Biosynthesis, IMBG NASU, Kyiv, Ukraine

since 2009 Head of the Laboratory of Systems Biology, DTMGI, IMBG NASU, Kyiv, Ukraine

Honours, Prizes, Awards:

19981999 Personal Grant from Jozef Mianowski Fund, Poland (2 months)

Personal Grant from UICC (Global Cancer Control), ICRET (International Cancer Technology Transfer Fellowships) N580, 2001 for the work in National Cancer Institute, NIH (National Institutes of Health), Bethesda, USA (3 months)

Research Areas:

  • Systems Biology. Bioinformatics:
  • Gene expression and its regulation in eukaryotic cells; Analysis of gene regulatory profiles obtained by microarray and NGS technology; Reconstruction of gene regulatory network; Alternative polyadenylation in the cellular adaptation
  • Approaches for Data Analysis in Systems Biology: Current Advances; Processing of Microarray Raw Data; Distributed Bayesian Networks in reconstruction of gene regulatory network; Curation of data

urrent Research Activities and Recent Achievements:

Systems Biology is a new trend at the beginning of XXI century. Systems Biology that is defined as the quantitative analysis of the dynamic interactions between the components of a biological system and aims at understanding the behavior of the system as a whole, as opposed to the behavior of its individual constituents [Dollery et al., 2007]. Systems Biology recognizes the system as a dynamic formation, which changes during its functioning and evolution. Systems Biology uses the high-throughput technologies of molecular biology, mathematics, physics, informatics and engineering. It handles the massive amounts of data; its measurements must be as quantitative as possible for the ultimate integration and modeling this information; it combines discovery-driven and hypothesis-driven approaches to systems studies; the modeling is the ultimate objective of systems biology that helps to understand the mechanistic underpinnings of particular biological systems phenomena that emerge from the integrated operation of the information components (emergent properties) [Hood et al., 2008].

Gene regulatory network: understanding the logic of preeclampsia development in health and disease

The human placenta is a unique temporary organ that originates from the trophectoderm of the blastocyst and develops into a complex functionally active structure that mediates the tight interactions between the fetus and the maternal organism. During the whole period of gestation placenta undergoes molecular, structural and functional rearrangements to meet the requirements of fetal and maternal organisms. The abnormalities in placental functions lead to the health problems for mother and child during gestation and after it. The syndrome of preeclampsia is one of the major complications of pregnancy (7 10%% worldwide) and the leading cause of maternal and fetal morbidity and mortality. While the exact cause of preeclampsia remains unclear, there is strong evidence that a major cause predisposing a susceptible woman to preeclampsia is an abnormally implanted placenta yielding a state of hypoxia and increased oxidative stress, the release of anti-angiogenic proteins along with inflammatory mediators into the maternal plasma and generalized endothelial dysfunction.

We focus our research on gene expression profile in human placenta from physiological and preeclampsia-affected pregnancy. For this end, we subdivided our research for four stages: 1.Data mining in open gene expression databases for the corresponding data of gene expression profiles and metadata and organization of available and additionally obtained metadata in specialized database (http://194.44.31.241:24173); 2. Organization of the various case-control groups using gene expression profiles from human placenta in health and disease; 3. Integrative analysis of genome wide gene expression profiles; 4. Reconstruction of gene regulatory networks characteristic for healthy and preeclampsia-affected human placenta. Gene expression profiling and gene regulatory networks provide the most global picture of the processes going on in placenta and help to understand the molecular mechanisms and signaling pathways controlling placenta development in health and preeclampsia.

Alternative polyadenylation in cellular adaptation to proliferation and differentiation

Proliferation and differentiation impose different biosynthetic requirements to support cell functions. In order to divide, a cell must provide support for the three basic needs of dividing cells: rapid ATP generation to maintain energy status; increased biosynthesis of macromolecules; and tightened maintenance of appropriate cellular redox status. To meet this demand the multiple molecular mechanisms converge to alter core cellular metabolism (e.g. Warburg effect, NADPH production). One remarkable feature of proliferating cells is the shortening of nearly 80 % of protein-coding mRNAs via alternative 3UTR polyadenylation (APA) that is regulated globally, simultaneously involving numerous transcripts in a cell. This was shown for different human tissues that display a biased preference APA isoform types and was demonstrated in studies of proliferation- and differentiation-based changes in APA profiles (developing embryos, activated and quiescent immune cells etc.). Neither the triggering mechanisms of mRNA shortening nor the benefits for proliferating cells are known so far.

We have focused on trifunctional gene GART responsible for the second, fifth and third reactions from ten sequential reactions of purine synthesis. GART transcripts exist in two forms the short one responsible for the second reaction and the long trifuctional one. We investigate the expression of both isoforms in the tissues with different proliferation activities; compare the 3UTR in both forms, identify the putative 3UTR-binding proteins. The physiological role of the short isoform we intend to study using the CRISPR technology.

Approaches for Data Analysis

The rapid development of high throughput technology in molecular/systems biology led to accumulation of enormous amount of data that ever grows. This situation urged biologists to address the methods of data science, namely scientific methods, processes, algorithms and systems to extract knowledge or insights from data in various forms, either structured or unstructured. To get information on gene expression profiles in human placenta in health and disease we extracted and organized data from open access data base Array express and constructed the specialized database after describing the data with standard annotation protocols and vocabularies that enable powerful queries and biological database inter-operability. The specialized database is automatically up-dated.

The direct data integration increases the size and the statistical power of gene expression estimation and forms the basis for the modelling of gene regulatory network, which can be seen as a practical embodiment of systems biology. To get the benefits of this approach we chose the optimal pipeline to microarray data processing to overcome the individual study-specific biases due to different microarray platforms, technical peculiarities etc. As reconstruction of gene regulatory database is a NP-hard task, we elaborated the parallelized algorithm and proposed its implementation in the improved version of BNFinder - tool for learning optimal Bayesian networks.

We set up the creation of standardized code to work with virtual machines on cloud and analyze the integrative data of gene expression

The innate immunity in liver regeneration and central nervous system

The liver is the largest solid organ in the body with dual inputs for its blood supply. It receives 80% of its blood supply from the gut through the portal vein, which is rich in bacterial products, environment toxins, and food antigens. The remaining 20% is from vascularization by the hepatic artery. Seventy percent of the cell number or 80% of the liver volume is composed of hepatocytes that fulfill the metabolic and detoxifying needs of the body. The remaining cells are made up of nonparenchymal cells, including endothelial cells, stellate cells, Kupffer cells, and lymphocytes. The liver successfully combines the role of a "biochemical laboratory" with the role of a major organ of innate immunity. In a physiologically relevant state, it eliminates antigens derived from the gastrointestinal tract, aging and transformed cells and reveals tolerance to their continuous presence (Crispe 2009). After the liver injury and the body injury not affecting the organ the liver responses by regeneration and acute phase response, respectively. Our recent studies revealed the transient upregulation of interferon α (IFNα) expression during the early hours after partial hepatectomy and differential expression of IFNα target genes, ISGylation-related genes, after partial hepatectomy and laparotomy. ISGylation-related genes are responsible for post-translational protein modification by the protein ISG15 inducing transient changes of protein functions. Their expression highlights the principal difference of acute phase response to both operations and raises the question of the regulation of these responses. The analysis of corresponding genes promoters with consequent chromatin immunoprecipitation is an exciting challenge.

The high-dose IFNA therapy is widely used for the treatment of hematological malignancies, multiple sclerosis and accompanied by side effects with largely undefined mechanisms of IFNα neurotoxicity. We applied self-elaborated tool COTRASIF (conservation-aided transcription-factor-binding site finder) for genome-wide bioinformatical search in rat and mouse genome for genes containing in their promoters IFN-stimulated response elements (ISRE) and discovered new putative target genes of IFNα, which encode the proteins involved in chemical synaptic transmission in central nervous system. The goal of the study is to verify the bioinformatical prediction and to find out the means to alleviate the IFNA therapy side effects based on newly discovered and experimentally confirmed target genes of IFNA in central nervous system.

People

Current members

  1. Obolenskaya M. Yu. head of laboratory, dr. hab., prof.
  2. Martsenyuk O. P. sc. researcher, Ph.D
  3. Rodrigues R. R. jun. sc.researcher
  4. Frolova A. O. jun. sc.researcher
  5. Lykhenko O. PhD student
  6. Ralchenko S. PhD student
  7. Chabanova M. V. technik
  8. Reznik R. student

Methods

Protocols

  • Cross-platform microarray data integration
  • Chromatin immunoprecipitation
  • Nuclear run-on assay
  • Evaluation of purine biosynthesis with mass-spectrometry
  • Estimation of SAM and SAH concentration with mass-spectrometry
  • Measurement of taurine in eukaryotic tissues with the help of mass-spectrometry
  • Cultivation of placental explants
  • Routine methods of molecular biology

Tools

Publications:

  • Lykhenko O, Frolova A and Obolenska M. Designing the Database for Microarray Experiments Metadata 2017 IEEE International Young Scientists Forum on Applied Physics and Engineering YSF-2017 October 17-20, 2017 Lviv, Ukraine
  • Lykhenko O, Frolova A and Obolenskaya MCreation of Gene Expression Database on Preeclampsia-Affected Human Placenta. Biopolym Cell. 2016. Vol. 32. N 3, p. 161172
  • Rodriguez R., O.Vakulenko, S.Ralchenko, A.Kostiuk, L.Porublyova, I.Konovets, I.Voronina, M.Obolenskaya. Quantification of S-adenosylmethionine and S-adenosylhomocysteine in human placenta and placental explants under homocysteine treatment. International journal of mass spectrometry International Journal of Mass Spectrometry 2017, 421: 279284.
  • Frolova A., Obolenska M. Integrative Approaches for Data Analysis in Systems Biology: Current Advances. In Applied Physics and Engineering (YSF), 2016 II International Young Scientists Forum on, pp. 194-198. IEEE, 2016.
  • M. Obolenskaya, A. Kuklin, R. Rodrigez, O. Martsenyuk, K. Korneyeva, V. Docenko, O. Draguschenko. Practical view on quantification of mRNA abundance using RT-qRCR, normalization of experimental data and MIQE. Biopolymers and Cell. 2016. Vol. 32. N 3.
  • K. L. Korneeva, R. R. Rodriguez, S. V. Ralchenko, O. V. Martunovska, A. . Frolova, O. P. Martsenyuk, L. V. Manzhu a, V. T. Melnyk, O. Y. Shkoropad, M. Yu. Obolenska. Expression of genes, encoding the enzymes of cysteine metabolism in human placenta in the first and third trimesters of uncomplicated pregnancy. Ukr. Biochem. J., 2016; 88 (1): 8898
  • Alina Frolova, Bartek Wilczynski. Fast Parallel Bayesian Networks Reconstruction with BNFinder. Proceedings of the IWBBIO International Work-Conference on Bioinformatics and Biomedical Engineering, Granada, April 7-9, pp. 1179-1184 (2014) ISBN 978-84-15814-84-9
  • M. Yu. Obolenskaya, B. T. Tokovenko, A. V. Kuklin, A. A. Frolova, R. R. Rodriguez, V. A. Dotsenko, O. O. Dragushchenko. The start of systems biology in Ukraine. Biopolym. Cell. 2014; 30(1): 1624
  • Kuklin A, Tokovenko B, Makogon N, Oczko-Wojciechowska M, Jarząb B, Obolenskaya M. Hepatocytes Response to Interferon Alpha Levels Recorded After Liver Resection. J Interferon Cytokine Res. 2014 Feb;34(2):90-9. doi: 10.1089/jir.2012.0125. Toxicol Lett. 2010 Jul 1;196(2):80-6. Epub 2010 Apr 7.
  • Slonchak A. M., Chwieduk A., Rzeszowska-Wolny J., Obolenskaya M. Yu. Regulation of Glutathione S-transferase expression in melanoma cells. Breakthroughs in Melanoma Research (ISBN 978-953-307-291-3) edited by Dr. Yohei Tanaka InTech, Vienna, Austria (2011), P. 145 156.
  • Mislanova C1, Martsenyuk O, Huppertz B, Obolenskaya M. Placental markers of folate-related metabolism in preeclampsia. Reproduction. 2011 Sep;142(3):467-76. doi: 10.1530/REP-10-0484. Epub 2011 Jun 20
  • Nadiya M. Teplyuk, Rao L. Divi, Miriam C. Poirier, Nataliya B. Filimonova, Monika Zadrozna, Markku J. Pasanen. Human placental glutathione S-transferase activity and polycyclic aromatic hydrocarbon DNA adducts as biomarkers for environmental oxidative stress in placentas from pregnant women living in radioactivity- and chemically-polluted regions. Toxicol Lett. 2010;196(2):80-6. doi: 10.1016/j.toxlet.2010.03.1115.
  • Tokovenko B, Golda R, Protas O, Obolenskaya M, El'skaya A. COTRASIF: conservation-aided transcription-factor-binding site finder. Nucleic Acids Research, 2009, 18 (doi:10.1093/nar/gkp084).
  • O. Martsenyuk, B. Huppertz, M. Siwetz, C. Mislanová, Obolenskaya M. Cytotoxicity of homocysteine and its transsulfuration pathway in human placenta. Biopolymers and cell. 2008. v.24, N5. P. 358.
  • Tokovenko B.T., Elskaya A. V., Obolenskaya M.Yu. In silico approach to study and functionally analyze interferon regulated genes. Biopolymers and Cell. 2007. - V.23, N 4. P. 368 375.
  • Teplyuk N., Prima V., Malko M., Bondarenko E., Didenko L., Vit V., Divi R., Poirier M., Pasanen M. Glutathionettransferase activity and PAH-DNA adducts in human placenta as a risk factor for new-born in radioactively contaminated regions. International Journal of Radiation medicine. 2004. V.6 (1-2). P.154-166.
  • Obolenskaya M., Samoilenko A. Does nitric oxide regulate the transduction of TNF signal? EOS - J. Immunology and Immunopharma cology. - 2000. - V.20, 1. - . 13-20.
  • Obolenskaya M. Cytokines and liver regeneration. EOS - J. Immunology and Immunopharmacology. - 1997. - V.17, 2. - . 51 -58.
  • T.L.Tchaikovskaya, L.M. Lebedeva, L.L. Macevitcz, L.V.Didenko, K.Decker. Glutathione status of placentae from differently polluted regions of Ukraine. European Journal of Obstetrics & Gynecology and Reproductive Biology. 1997. V.71, N 1. P.23-30.
  • Obolenskaya M.Yu., Bernauer H., Tran - Thi T.-A., Decker K. Levels of RNA for TNF- and TNF receptors during the prereplicative period of liver regeneration. Biopolym. Cell. - 1994. - .10, 4. - C. 152 156.
  • Decker K., Obolenskaya M. Cytokines, nitric oxide synthesis and liver regeneration. J. Gastroenterology and Hepatology. - 1995. - 10. - S12-S17.
  • Obolenskaya M., Schulze-Specking A., Plaumann B., Frenzer K., Freudenberg N. and K. Decker. Nitric oxide production by cells isolated from regenerating rat liver. Biochem.Biophys. Res. Comm. - 1994. - V. 204, 3. - . 1305 1311.
  • Obolenskaya M., Vanin A.F., Mordvintcev P.I., Mulsch A., Decker K. EPR evidence of nitric oxide production by the regenerating rat liver. Biochem. Biophys. Res. Comm. - 1994. - V. 202, 1. - . 571 - 576

PhD Theses

  • Transcriptional factors genes and B2 DNA sequences expression in regenerating rat liver (Lesya Novikova)
  • Glutathionetransferase activity and DNA-adducts in human placenta in radioactively and chemically polluted environment (Nadiya Teplyuk)
  • Cell-specific particularities of the human glutathione S-transferase gene transcription regulation (Andrij Slonchak)
  • Design and implementation of the insilico methods to identify eukaryitic transcription factor binding sites (Bogdan Tokovenko)
  • Folate-related processes in human placenta: role of folic acid, homocysteine and polymorphism of methylenetetrahydrofolate reductase gene (Olga Martsenyuk)
  • Changes in expression of innate immunity related genes in intact hepatocytes and rat liver of during regeneration (Andrij Kuklin)

Browse data (in progress)

  • 4C-seq data browser: Genome browser featuring all 4C-seq view points published in Ghavi-Helm et al.
  • ChIP-on-chip: This link allows you to search ChIP-on-chip data for transcription factor binding in the vicinity of your gene of interest.
  • Expression Profiling: The affect of a loss of function mutation on the expression of a gene can be visualized as either a histogram or a spline.

International Grants:

  1. Joint Ukraine India grant R&D projects. India-ukraine intergovernmental
  2. science & technology cooperation program. Cross-talk of modifying enzymes TRIM in regulation of interferon alpha and cell survival in regenerating liver /208-2015 2017
  3. STCU Grant N 4381 New technologies in the study of interferon alpha functional activity (2007 2009)
  4. Grant from scientific and technological cooperation Ukraine Slovakia Folate-and detoxication activity in human placenta from environmentally exposed pregnancies /28 2008 (2008 2009
  5. Grant from scientific and technological cooperation Ukraine Slovakia Polluted environment and genotoxic damage of human placenta 152 - 2006 (2006 2007)
  6. INTAS grant for young scientists 06-1000014-5961 Folate-related one-carbon unit metabolism in human placenta from environmentally exposed pregnancies (2008 = 2009)
  7. Grant frm Polish Ministry of science and education 40115732/3043 Regulation of GSTP1 expression in human placenta from environmentally exposed pregnancies
  8. UICC (ICRET N580, 2001)DNA adducts in placentas of environmentally exposed pregnancies
  9. Grant from International Federation of scientists in the area Medicine Interferon alpha and its role in liver cells transition from quiescence to proliferation (2006 2007)
  10. Short-term UNESCO grants (M.Perepelyuk,2006; B.Tokovenko,2007; A.Slonchak, 2008; A.Kuklin2009)

National Grants:

Projects of National Academy of Sciences of Ukraine:

  1. - -㳿 - 2017 -2018
  2. Grant 69-53 Development of Ensemble method with high rate of parallelization for gene regulatory modeling in GRID environment(2012)
  3. Grant 1646 Design of new highly parallelized GRID-methods of gene regulatory networks modeling for systems analysis of liver response to interferon alpha (2011)
  4. Grant 1646 Elaboration of new methods of GRID calculations with high rate of parallelization for systems analysis of liver regeneration by gene regulatory modeling on the basis of large-scale study of gene expression (2010)
  5. Grant for talented youth from President of Ukraine Estimation of risk factors for preecalmpsa development and the markers for early diagnosis (2013)
  6. Grant for talented youth from President of Ukraine Biomarkers for prevention of pregnancys complications (2006)