Group of system biology

Head

Maria Yu. Obolens'ka

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

Education and Degrees:

1958–1964 Graduate Student, Bogomolets National Medical University, Kyiv, Ukraine

1964–1967 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:

1964–1975 Junior Research Scientist, Department of Molecular Biology, D. F. Chebotarev State Institute of Gerontology, NAMSU, Kyiv, Ukraine

1975–1980 Research Scientist, Department of Molecular Mechanisms of Protein Biosynthesis, Institute of Molecular Biology and Genetics (IMBG), NASU, Kyiv, Ukraine

1980–1991 Senior Research Scientist, Department of Molecular Mechanisms of Protein Biosynthesis, IMBG NASU, Kyiv, Ukraine

1991–1994 Research Scientist, Institute of Molecular and Cell Biology, Albert-Ludwig University, Freiburg i. Br., Germany

1994–1999 Senior Research Scientist, group leader, Department of Translational Mechanisms of Genetic Information (DTMGI), Laboratory of Protein Biosynthesis, IMBG NASU, Kyiv, Ukraine

2000–2009 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:

1998–1999 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: Whole genome search for target genes of transcription factors; Reconstruction of gene regulatory networks. Theoretical predictions and experimental corroborations

Gene expression and its regulation in eukaryotic cells

Ñurrent Research Activities and Recent Achievements:

Systems analysis of non-canonical functions of interferon alpha.

The regulation of gene expression at the transcriptional level relies upon the effects of the transcription factors (TF) bound to specific regulatory elements. Experimental identification of TF binding sites within single-gene promoters is effort- and time-consuming with no prior information. We have elaborated a genome-wide finder of regulatory elements in promoters of protein coding genes available at http://biomed.org.ua/COTRASIF/. The application of this tool to the search for potential target genes of prior response to interferon alpha (IFNα) has revealed several previously “unknown” genes referring to the central nervous and compliment systems. Experimental verification of theoretically anticipated genes is in the focus of our current investigations. The modern systematic approach to capture the behavior of cellular genome is to develop the mathematical model of gene regulatory network (GRN) where the nodes are the genes and the edges represent interactions between genes via mRNAs and proteins. The reconstruction is based on the data of gene expression profiling by microarray or next generation sequencing and ever developing methods of bioinformatics. To get the GRN in rat hepatocytes treated with IFNα we conducted microarray experiment and elaborated Ensemble method for the GRN reconstruction (see source code and data repository at http://github.com/sysbio-vo/).

Fig. 1. Time-dependent response of differentially expressed genes in rat hepatocytes to IFNα. The square of the big sectors (colored plus white parts) is proportional to the number of differentially expressed genes after 6 h of hepatocytes treatment with IFNα and the square of the inner unshaded sectors – to the number of genes after 3 h treatment.
Gene expression during transition of liver cells from quiescence to proliferation induced by partial hepatectomy in rats.

The liver conscientiously and successfully combines the role of “biochemical laboratory” with the role of a major organ of innate immunity. The hepatic cells constantly eliminate the antigens derived from gastrointestinal tract, aging and transformed cells and reveal self-tolerance to their continuous presence. Extensive damage of liver parenchyma, transplantation, when the transplanted organ is too small to cope with metabolic demands or classical 70 % partial hepatectomy (PH) reverse the tolerance and induce an innate immunity response manifested by complement activation, cytokine production, expansion of natural killer cells, activated signaling from several Toll-like receptors and inhibitory signaling from signal transducing and activator factor 3 preventing liver failure. We have suggested a definite role of interferon alpha (IFNα) in triggering liver restoration. Our recent studies have proved this idea revealing transient up-regulation of IFNα mRNA and IFNα- specific antiviral activity during 1 – 6 h post-PH preceding the presynthetic period of hepatocytes cell cycle. The activation of intracellular IFNα signaling after PH corroborated our results (Chen and others 2010). The current activity is focused on the study of expression of target genes of IFNα at the beginning of liver restoration.

Fig. 2. Fold change of IFNα specific mRNA content in hepatocytes and nonparenchymal cells after partial hepatectomy (A) and laparatomy (B)
Folate-related metabolism of onecarbon units in human placenta.

Folate-related one-carbon unit metabolism (FOCM) is a basic metabolic network tightly connected with essential cell functions – proliferation, differentiation, maintenance of redox status, all processes of methylation, etc. The experimental study of each chain of the system with various alterations of its multiple components is a laborious and expensive task though the general behavior of the system is greatly required by clinicians. The function of FOCM is tissue-specific and primarily dependent on activities of its highly polymorphic enzymes, vitamins B, folic acid and amino acids supply. The marker of FOCM is a level of homocysteine which is up-regulated during cardiovascular diseases, pregnancy pathologies, and mental disorders. We created stoichiometric mathematical model of FOCM in human placenta, taking into account the tissuespecific characteristics of corresponding genes expression, simulated the pathological situations typical for obstetrics pathologies and analyzed the whole network behavior. The results of analysis have revealed: firstly, the reliability of the model for predictions of network behavior as some of predicted characteristics correspond to experimentally obtained ones in the most studied clinical pathologies; secondly, the obtained predictions of the network behavior in slightly investigated situations will serve as a road map for the further studies and introduction of results into clinical practice.

Fig. 3. Changes of metabolic fluxes in folate-related metabolism at twofold overload of human placenta with homocysteine Folate and methionine cycles are represented at the figure. The decrease of metabolic fluxes is marked with blue color and increase – with red color. The more thick are the arrows the more pronounced is the increase of the flux and more thin are the arrows the more pronounced is the decrease of the flux

National Grants:

Projects of National Academy of Sciences of Ukraine:

  • 2012 N 69-53 Project: “Development of Ensembl method with high rate of parallelization for gene regulatory modeling in GRID environment”
  • 2011 N Ã16–46 Project: “Design of new highly parallelized GRID-methods of gene regulatory networks modeling for systems analysis of liver response to interferon alpha”
  • 2010 N Ã16–46 Project: “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”

Grants of Ministry of Education and Science of Ukraine:

  • 2013 Grant for talented youth from President of Ukraine “Estimation of risk factors for preecalmpsa development and the markers for early diagnosis”
  • 2006 Grant for talented youth from President of Ukraine “Biomarkers for prevention of pregnancy’s complications”

International Grants:

  • 2008–2009 N Ì/28-2008 Grant from scientific and technological cooperation Ukraine – Slovakia “Folate-and detoxication activity in human placenta from environmentally exposed pregnancies”
  • 2008–2009 INTAS (The International Association for the Promotion of Co-operation with Scientists from the New Independent States of the Former Soviet Union) Grant for young scientists N 06-1000014-5961 “Folate-related one-carbon unit metabolism in human placenta from environmentally exposed pregnancies”
  • 2007–2009 STCU (Science and Technology Center in Ukraine) N 4381 Project: “New technologies in the study of interferon alpha functional activity”
  • 2006–2009 UNESCO (United Nations Educational, Scientific and Cultural Organization) Short-term Grants (M.Perepelyuk, 2006; B.Tokovenko, 2007; A.Slonchak, 2008; A.Kuklin, 2009)
  • 2006–2007 Grant from scientific and technological cooperation Ukraine – Slovakia N 152-2006 “Polluted environment and genotoxic damage of human placenta”
  • 2006–2007 Grant from International Federation of Scientists in the area Medicine “Interferon alpha and its role in liver cells transition from quiescence to proliferation”
  • 2001 UICC, ICRET N 580 Project: “DNA adducts in placentas of environmentally exposed pregnancies”
  • Grant form Polish Ministry of science and education N 40115732/3043 “Regulation of GSTP1 expression in human placenta from environmentally exposed pregnancies”

Collaboration:

with Ukrainian organizations:

  • State Institution “L. V. Gromashevsky Institute of Epidemiology and Infectious Diseases of NAMS of Ukraine” (Kyiv)
  • Bogomoletz Institute of Physiology, NASU (Kyiv)

with foreign organizations:

  • University of Warsaw, Institute of Informatics (Warsaw, Poland)
  • Institute of Cell Biology, Histology and Embryology, Medical University of Graz (Graz, Austria)

Selected publications:

  1. Korneeva, K. L., R. R. Rodriguez, S. V. Ralchenko, O. V. Martunovska, A. Î. Frolova, O. P. Martsenyuk, L. V. Manzhula, V. T. Melnyk, O. Y. Shkoropad, and M. Yu Obolenska. Expression of genes, encoding the enzymes of cysteine metabolism in human placenta in the first and third trimesters of uncomplicated pregnancy. The Ukrainian Biochemical Journal 88, 1 (2016): 88-98.
  2. M. Yu. Obolenskaya, B. T. Tokovenko, A. V. Kuklin, A. A. Frolova, R. R. Rodriguez, V. A. Dotsenko, O. O. Dragushchenko. Practical approach to quantification of mRNA abundance using RT qPCR, normalization of experimental data and MIQE. Biopolymers and Cell. 2016. Vol. 32. N 3. P 161–172 doi: http://dx.doi.org/ 10.7124/bc.00091A.
  3. Alina Frolova, Maria Obolenska. Integrative Approaches for Data Analysis in Systems Biology: Current Advances. In proceedings of II International Young Scientists Forum on applied physics and engineering, October 10-14, 2016, Kharkiv, Ukraine: 15-20.
  4. Bondarenko V, Obolenska MYu. Bioinformatics analysis of cis-regulatory elements in Mbl1 and Mbl2 genes in Rattus norvegicus. Biopolymers and Cell. 2015; 31(1):63–70.
  5. A. V. Kuklin, T. A. Poliezhaieva, I. O. Zhyryakova, M.Yu. Obolenskaya. Expression of ISGylation related genes in regenerating rat liver. Biopolymers and Cell. 2015; 31.
  6. Kuklin A, Tokovenko B, Makogon N, Malgorzata Oczko-Wojciechowska. Hepatocytes Response to Interferon Alpha Levels Recorded After Liver Resection. Journal of Interferon & Cytokine Research. 2014;34(2):90-100.
  7. Obolenskaya MYu, Tokovenko BT, Kuklin AV, et al. The start of systems biology in Ukraine. Biopolym. Cell. 2014;30(1):16–24.
  8. Obolenska MYu. Systems Biology and project ENCODE. Ukr. Biochem. J. 2014;86(4):5-17.
  9. Dotsenko VA, Obolenskaya MYu. Mathematical modeling of folate-related processes in human placenta. Biopolym. Cell. 2014;30(2):149-156.
  10. Frolova A., Bartek Wilczynski. Fast Parallel Bayesian Networks Reconstruction with BNFinder. Proceedings of the IWBBIO International Work-Conference on Bioinformatics and Biomedical Engineering, Granada. Copicentro Granada. ISBN 978-84-15814-84-9. April 7-9, 2014; 1179-1184.
  11. Dragushchenko O, Markadeiev M, Obolenska MY. Gene Mbl1 is a target of interferon alpha. FEBS Journal. 2013; 280 (Suppl. 1): 80–81.
  12. Frolova AO. Overview of methods of reverse engineering of gene regulatory networks: Boolean and Bayesian networks. Biopolym. Cell. 2012; 28(3): 163–170. doi:10.7124/bc.000036
  13. Rodriguez RR, Lushchyk IS, Obolenska MYu.Stoichiometric model of folate­dependent metabolism of one­carbon units in human placenta. Ukr Biokhim Zh. 2012 Jul­Aug; 84(4):20–31.
  14. Slonchak AM, Chwieduk A, RzeszowskaWolny J, Obolenskaya MYu Regulation of Glutathione Stransferase expression in melanoma cells. In: Yohei Tanaka, editor. Breakthroughs in Melanoma Research. Vienna, Austria: InTech; 2011. p. 145–156. doi:10.5772/18747
  15. Mislanova C, Martsenyuk O, Huppertz B, Obolenskaya M. Placental markers of folate­related metabolism in preeclampsia. Reproduction. 2011; 142(3):467–76. doi:10.1530/REP-10-0484
  16. Obolenskaya M.Yu., Rodriguez R.R., Martsenyuk O.P. Folate related processes in human placenta: gene expression, aminothiols, proliferation and apoptosis. Ukr Biokhim Zh. 2011, 83(1):6–17.
  17. Obolenskaya MY, Teplyuk NM, Divi RL, Human placental glutathione Stransferase activity and polycyclic aromatic hydrocarbon DNA adducts as biomarkers for environmental oxidative stress in placentas from pregnant women living in radioactivity and chemicallypolluted regions. Toxicol Lett. 2010; 196(2):80–6. doi:10.1016/j.toxlet.2010.03.1115
  18. Dragushchenko O. O., Tokovenko B. T., Obolenskaya M. Yu. Primary analysis of results of whole genome search for genes of response to the effect of interferon alpha. Ukr Biokhim Zh. 2010; 82(1):82–9.
  19. Tokovenko B, Golda R, Protas O, Obolenskaya M., El'skaya A. COTRASIF: conservationaided transcriptionfactorbinding site finder. Nucleic Acids Res. 2009; 37(7):e49. doi:10.1093/nar/gkp084
  20. Porubliova LV, Rebriev AV, Gromovoy TYu, Minya IY, Obolenskaya MYu. MALDITOF massspectrometry in investigation of highmolecular biological compounds. Ukr Biokhim Zh. 2009; 81(3):46–56.