Group of Systems Biology

Head

Maria Yu. Obolens'ka

Professor, Dr. Sci. (Mol. Biol.)
Тел.: (380-44) 200-03-67
Факс: (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

2009-2016 Head of the Laboratory of Systems Biology, DTMGI, IMBG NASU, Kyiv, Ukraine

since 2016 Head of the Group of Systems Biology, Department of Protein Synthesis Enzymology, 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
  • 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

About:

The beginning of the XXI century was marked by the emergence of the new branch in biological sciences – systems biology that aims to understand the system's behavior as a whole instead of its parts. Systems biology uses the information obtained by molecular biology, biochemistry, physiology, mathematics, and informatics for the ultimate integration of multifaceted information and building a comprehensive model of the biological system. The investigation of origin and development of multifactorial diseases became the burning question for systems biology. In 2009, the first laboratory of Systems Biology in Ukraine (Prof. Maria Obolenskaya) was organized in the Institute of Molecular Biology and Genetics of the National Academy of Sciences of Ukraine.

Research:

Preeclampsia is a worldwide pregnancy complication with high morbidity and mortality

Preeclampsia is a typical multifactorial pregnancy complication, affecting 5 – 10 % of pregnant women worldwide. The cause of preeclampsia is a placental dysfunction connected with genetic, environmental, and predisposing factors, including lifestyle, although the exact etiology and pathogenesis of the disease are still unknown. Preeclampsia-related changes in the human placenta were recorded at different layers of gene expression and regulation such as genome, epigenome, proteome, and metabolome. Data on the transcriptome of placental tissues, various components of the uteroplacental complex, and types of single cells represent the overwhelming majority among already published multi-omics data. The independent studies suffer from inherent statistical limitations because of small sample size. Combining multiple studies increases the reproducibility and sensitivity of the research and the statistical power of conclusions. Our study aims to integrate the data on the gene expression level in the human placenta from independent publicly available studies of normotensive and preeclampsia-affected pregnancies. The analysis of differentially expressed genes in health and disease in the course of gestation is the ultimate goal. Here is a brief roadmap of our research:

  1. Creation of placenta-specific database on gene expression in health and disease (complete, now available at igea.sysbio.org.ua).

  2. Gene expression in bulk placental tissue from normotensive pregnancy during gestation based on microarray data from 77 samples (complete).

    3. We have revealed 253 (152 up- and 101 down-regulated) and 489 (221 up- and 268 down-regulated) differentially expressed genes between II and I trimesters and III and II trimesters, correspondingly. The respective protein interaction graphs with clusters named according to biological processes are given below [Lykhenko et al., 2021 a,b,c].

    Fig.1 Protein-protein interactions between the products of differentially expressed genes in placental samples from first and second trimesters of gestation.

    Fig.2 Protein-protein interactions between the products of differentially expressed genes in placental samples from third and second trimesters of gestation.

  3. Gene expression in bulk placental tissue from preeclampsia-affected pregnancy based on microarray and RNA-seq data (in progress).
  4. Role of smoking in preeclampsia risk reduction (in progress).
  5. Analysis of gene expression in the components of utero-placental complex (chorion, decidua), single cells, and maternal and fetal blood; analysis of proteome and metabolome; new NGS experiment (planned).
  6. Extending capabilities of the IGEA website user interface: integration of multiple datasets, differential gene expression analysis, biological interpretation (planned).
  7. Integrating several microarray-based gene expression datasets while not excluding genes that are not present in all datasets (gene expression imputation). This improved technique would allow for a large scale data integration (planned).

Methodological approaches: integrative analysis of gene expression from independent data, sex determination from gene exepression data [Lykhenko et al., 2021a,c].

Environmental metagenomics: the study of urban biomes

We are a part of the international MetSUB consortium that aims to build a molecular profile of cities around the globe to improve their design, functionality, and impact on health. Public transportation systems represent the densest interaction space for millions of people each day, and yet, there is little known about the dynamics of the microbiome and metagenomics profile on these surfaces, and most importantly, how these dynamics and our interactions with these surfaces can impact an individual’s health, as well as the health of a city.

The microbiome is the ecosystem of microorganisms that live on, in, and around us. The metagenome is the collection of all the DNAs surrounding us, humans, bacteria, viruses, plants, animals, etc. Many studies have shown that there is a link between the microbiome and human health.

Grid and Cloud Computing

  • Adaptation of cloud technologies for use in gene expression analysis
  • Creation of services for users

National Grants:

    Projects of National Academy of Sciences of Ukraine:

  • 2017-2021 “Grid infrastructure and grid technologies for scientific and scientific-applied applications” and “Informatization program of the National Academy of Sciences of Ukraine”
  • 2017 "Creation of a virtual center of digital science"
  • 2018-2020 “Cloud grid service for integrative cross-experimental analysis of gene expression”
  • 2021 "Adaptation of modern bioinformatics approaches for analysis and visualization of large-scale molecular biological data for use in the cloud environment"

    Projects of the Ministry of Education and Science of Ukraine:

  • 2013 Project for talented youth: Grant of the President of Ukraine "Determination of risk factors for the development of preeclampsia and markers of early diagnosis"
  • 2006 Project for Talented Youth: Grant of the President of Ukraine “Biomarkers for Prevention of Pregnancy Complications”

International Grants:

  • 2019-2020 Joint Austria-Ukraine research project “Detection of Antimicrobial Resistances and their Dissemination Potential in Urban Metagenome Samples“, M/84-2019, M/126-2020.
  • 2016-2017 Joint India-Ukraine research project “Cross-talk of modifying enzymes TRIM in regulation of interferon alpha and cell survival in regenerating liver”, М/31-2016; М/190 -2017.
  • 2008-2009 Grant from scientific and technological cooperation Ukraine – Slovakia "Folate-and detoxification activity in human placenta from environmentally exposed pregnancies" М/28-2008
  • 2008-2009 INTAS Grant for young scientists №06-1000014-5961 "Folate-related one-carbon unit metabolism in human placenta from environmentally exposed pregnancies"
  • 2007-2009 STCU Grant N 4381 "New technologies in the study of interferon alpha functional activity"
  • 2006-2007 Grant from scientific and technological cooperation Ukraine – Slovakia "Polluted environment and genotoxic damage of human placenta" №152-2006
  • 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"
  • Short-term UNESCO Grants (M.Perepelyuk, 2006; B.Tokovenko, 2007; A.Slonchak, 2008; A.Kuklin, 2009)
  • 2001 UICC (ICRET N580) "DNA adducts in placentas of environmentally exposed pregnancies"
  • Grant form Polish Ministry of science and education № 40115732/3043 "Regulation of GSTP1 expression in human placenta from environmentally exposed pregnancies"

Collaboration:

    with Ukrainian organisations:
  • SI «L.V. Gromashevsky Institute of Epidemiology and Infectious Diseases of the NAMS of Ukraine», Kyiv, Ukraine
  • Bogomoletz Institute of Physiology of NASU, Kyiv, Ukraine
  • Palladin Institute of Biochemistry of NASU, Kyiv, Ukraine
  • Bogolyubov Institute for Theoretical Physics of NASU, Kyiv, Ukraine
  • Kyiv Academic University, Kyiv, Ukraine
    with International organisations:
  • University of Applied sciences, FH Campus Wien
  • Institute of Informatics, University of Warsaw
  • The Division of Cell Biology, History and Embryology, Medical University of Graz, Austria
  • MetaSUB Consortium - Metagenomics & Metadesign of Subways & Urban Biomes

Publications:

  1. Kalashnyk, O., Lykhmus, O., Koval, L., ...Komisarenko, S., Skok, M. α7 Nicotinic acetylcholine receptors regulate translocation of HIF-1α to the cell nucleus and mitochondria upon hypoxia. Biochemical and Biophysical Research Communications, 2023, 657, pp. 35–42
  2. Stepanov, I., Ivasiuk, A., Yavorskyi, O., Frolova, A. Comparative analysis of classification techniques for topic-based biomedical literature categorisation. Frontiers in Genetics, 2023, 14, 1238140
  3. Wolfsberger, W., Chhugani, K., Shchubelka, K., ...Mangul, S., Oleksyk, T.K. Scientists without borders: Lessons from Ukraine. GigaScience, 2023, 12, giad045
  4. Forstner, D., Guettler, J., Brugger, B.A., ...Herse, F., Gauster, M.CD39 abrogates platelet-derived factors induced IL-1β expression in the human placenta. Frontiers in Cell and Developmental Biology, 2023, 11, 1183793
  5. Ivashchenko, O.V., Maci, M., Dziuba, D., ...Reinsone, S., Wolfsberger, W.W. Remote opportunities for scholars in Ukraine. Science, 2022, 378(6626), pp. 1285–1286
  6. Ryon, K.A., Tierney, B.T., Frolova, A., ...Sezer, Z.H., Mason, C.E. A history of the MetaSUB consortium: Tracking urban microbes around the globe. iScience, 2022, 25(11), 104993
  7. Wu, J., Danko, D., Afshinnekoo, E., ...Mason, C., Shi, T. Annotating unknown species of urban microorganisms on a global scale unveils novel functional diversity and local environment association. Environmental Research, 2022, 207, 112183
  8. Danko, D., Bezdan, D., Afshinnekoo, E., Ahsanuddin, S., Bhattacharya, C., Butler, D. J., … Frolova, A.O., ... & International MetaSUB Consortium. A global metagenomic map of urban microbiomes and antimicrobial resistance. Cell, 2021; 13(184), pp. 3376-3393.e17. DOI 10.1016/j.cell.2021.05.002.
  9. Lykhenko O., Frolova A. , and Obolenska M. a) Сonsecutive Integration Of Available Microarray Data For Analysis Of Differential Gene Expression In Human Placenta. Biotechnologia Acta. 2021; 14 (1): 38-45.
  10. Lykhenko OK, Frolova AO , and Obolenskaya MYu. b) Сhanges in the human placental transcriptome during the physiological course of pregnancy. Biopolym.Cell 2021;37 (1): 73 - 82.
  11. Lykhenko OK, Obolenskaya MYu. ISSN 1025-6415. c) The Knowledge Of Chromosomal Sex Is Important for Large-scale Analysis of Gene Expression. Dopov. Nac. akad. nauk Ukr. 2021. № 1: 100—109.
  12. Obolenskaya M, Dotsenko V, Martsenyuk O, Ralchenko S, Krupko O, Pastukhov A, Filimonova N, Starosila D, Chernykh S, Borisova T. A new insight into mechanisms of interferon alpha neurotoxicity: Expression of GRIN3A subunit of NMDA receptors and NMDA-evoked exocytosis. Prog Neuropsychopharmacol Biol Psychiatry. 2021 Mar 27;110:110317. doi: 10.1016/j.pnpbp.2021.110317. Epub ahead of print. PMID: 33785426.
  13. Rodriguez R, Konovets I, Ralchenko S, Kharkhota M, Kostyuk A, Kosach V, Voronina I, Filimonova N, Obolenskaya M. A low-cost mass spectrometry-based approach for quantifying purines in placental explants. International Journal of Mass Spectrometry. 2021; 460: 116490. https://doi.org/10.1016/j.ijms.2020.116490
  14. Hodorová, V., Lichancová, H., Zubenko, S., Sienkiewicz, K., Penir, S. M. U., Afanasyev, P., ... & Nosek, J. Genome sequence of the yeast Saprochaete ingens CBS 517.90. Microbiol Resour Announc. 2019 Dec 12;8(50):e01366-19. doi: 10.1128/MRA.01366-19.
  15. Birukov A, Muijsers HEC, Heidecke H, Drost JT, Cunnigham MW, Kraker K, Haase N, Frolova A, Müller DN, Herse F, Maas AHEM, Dechend R. Regulatory antibodies against GPCR in women ten years after early-onset preeclampsia. Front Biosci (Landmark Ed). 2019;24:1462-1476.
  16. Taylor, D.M., Aronow, B.J., Tan, K., Bernt, K., Salomonis, N., Greene, C.S., Frolova, A., Henrickson, S.E., Wells, A., Pei, L. and Jaiswal, J.K., The Pediatric Cell Atlas: defining the growth phase of human development at single-cell resolution. Developmental cell, 2019; 49 (1):10-29. https://doi.org/10.1016/j.devcel.2019.03.001
  17. Nonn O, Güttler J, Forstner D, Maninger S, Zadora J, Balogh A, Frolova A, Glasner A, Herse F, Gauster M. Placental CX3CL1 is Deregulated by Angiotensin II and Contributes to a Pro-Inflammatory Trophoblast-Monocyte Interaction. Int J Mol Sci. 2019;20(3):641. doi: 10.3390/ijms20030641.
  18. Frolova, Alina, and Bartek Wilczyński. "Distributed Bayesian networks reconstruction on the whole genome scale." PeerJ. 2018; 6: e5692.
  19. Kateryna Uspenska, Olena Lykhmus, Maria Obolenskaya, Stephanie Pons, Uwe Maskos, Serhiy Komisarenko, Maryna Skok. Mitochondrial Nicotinic Acetylcholine Receptors Support Liver Cells Viability After Partial Hepatectomy. Front Pharmacol. 2018; 9:626. doi: 10.3389/fphar.2018.00626. eCollection 2018
  20. Lykhenko O., Frolova A. O. & Obolenskaya M. Yu. Creation of gene expression database on preeclampsia-affected human зlacenta. Biopolym Cell. 2017; 33 ( 6):442–452 doi: http://dx.doi.org/10.7124/ bc.000967
  21. R. Rodriguez, 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 2017; 421: 279-284. doi.org/10.1016/j.ijms.2017.08.002
  22. Korneeva KL, Rodriguez RR, Ralchenko SV, Martunovska OV, Frolova AO, Martsenyuk OP, Manzhula LV, Melnyk VT, Shkoropad OY, Obolenska MY. 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):88-98. doi: 10.15407/ubj88.01.088
  23. A. Frolova and M. Obolenska, "Integrative approaches for data analysis in systems biology: Current advances," 2016 II International Young Scientists Forum on Applied Physics and Engineering (YSF), 2016; pp. 194-198, doi: 10.1109/YSF.2016.7753835
  24. Bondarenko V, Obolenska MYu. Bioinformatics analysis of cis-regulatory elements in Mbl1 and Mbl2 genes in Rattus norvegicus. Biopolym Cell 2015; 31(1):63–70.
  25. Kuklin A. V., Poliezhaieva T. A., Zhyryakova I. O., Ogryzko V. V., Obolenskaya M. Yu. Expression of ISGylation related genes in regenerating rat liver. Biopolym Cell 2015; 31 (5):351 - 361..
  26. 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;34(2):90-9. doi: 10.1089/jir.2012.0125.
  27. Obolenskaya MYu, Tokovenko BT, Kuklin AV, et al. The start of systems biology in Ukraine. Biopolym. Cell 2014;30(1):16–24.
  28. Obolenska MYu. Systems Biology and project ENCODE. Ukr. Biochem. J. 2014;86(4):5-17.
  29. 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
  30. Rodriguez RR, Lushchyk IS, Obolenska MYu.Stoichiometric model of folate dependent metabolism of one carbon units in human placenta. Ukr. Biochem. J. 2012; 84(4):20–31.
  31. 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
  32. Mislanova C, Martsenyuk O, Huppertz B, Obolenskaya M. Placental markers of folate related metabolism in preeclampsia. Reproduction. 2011; 142(3):467–76. doi:10.1530/REP-10-0484
  33. Obolenskaya MY, Teplyuk NM, Divi RL, 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 chemicallypolluted regions. Toxicol Lett. 2010; 196(2):80–6. doi:10.1016/j.toxlet.2010.03.1115
  34. 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. Biochem. J. 2010; 82(1):82–9.
  35. 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
  36. Porubliova LV, Rebriev AV, Gromovoy TYu, Minya IY, Obolenskaya MYu. MALDITOF mass spectrometry in investigation of high molecular biological compounds. Ukr. Biochem. J. 2009; 81(3):46–56.