Laboratory of Molecular Microbiology

Nina V. Tikunova,
D.Biol.Sci.
Phone: +7(383)363-51-57
Email

• Genomics of pathogens transmitted by ticks.
• Development of new immunotherapeutic preparations.
• Investigation of antibody repertoires circulating in human blood in case of pathology and healthy organisms using combinatorial techniques.
• Biodiversity of microbial communities of extremophiles.
• Study of molecular epidemiology of gastro viruses in Western Siberia.

• For the first time, RNA of Kemerovo virus, causing encephalitis-like disease in humans, was found in ixodes ticks in Novosibirsk region and Altai For the first time RNA of this virus in Ixodes pavlovskyi was found.. Molecular-genetic divergence of infectious agents transmitted by ticks was studied in Siberian region.
• Humanized antibodies against tick-borne encephalitis virus able to protect model animals were constructed. Fully human antibodies against ectromelia virus capable to neutralize pathogenic orthopoxviruses were developed. Single-chain antibodies against tumor necrosis factor, interleukin 18 and interferon-gamma were obtained and their immunochemical properties were estimated.
• Autoimmune, immune and naïve phage display libraries of human single-chain antibodies were constructed. Single-chain antibodies against myelin basic protein were selected. It was shown that repertoires of antibodies against interferon-gamma, ciculating in organisms of healthy people and patients with multiple sclerosis were significantly different.
• Etiological role of rotaviruses A and C, noro-, astro-, adenoviruses, pathogenic bacteria and causative agents in acute gastroenteritis in young children in Novosibirsk was investigated. Epidemiology of rota-, noro- and astrovirus infections was analysed. Genetic analysis of rota-, noro- and astrovirus isolates identified in Western Siberia was performed; circulating of genetic variants of those viruses during last years was found; circulation of rotaviruses of different genotypes during a single epidemic season were shown in Novosibirsk and Omsk. A laboratory variant of multiplex PCR kit for detection of astro-, boca- and rotavirus group C was made.

1. Lomakin Y.A., Zakharova M.Y., Stepanov A.V., Dronina M.A., Smirnov I.V., Bobik T.V., Pyrkov A.Y., Tikunova N.V., Sharanova S.N., Boitsov V.M., Vyazmin S.Y., Kabilov M.R., Tupikin A.E., Krasnov A.N., Bykova N.A., Medvedeva Y.A., Fridman M.V., Favorov A.V., Ponomarenko N.A., Dubina M.V., Boyko A.N., Vlassov V.V., Belogurov Jr A.A., Gabibov A.G. Heavy-light chain interrelations of MS-associated immunoglobulins probed by deep sequencing and rational variation. Mol Immunol. 2014: S0161-5890(14)00023-6.
2. Babkin I.V., Tikunov A.Yu., Sedelnikova D.A., Zhirakovskaia E.V., Tikunova N.V. Recombination analysis based on the HAstV-2 and HAstV-4 complete genomes. Infect Genet Evol. 2014. 22. 94-102.
3. Tyumentseva M.A., Morozova V.V., Lebedev L.R., Babkin I.V., Tikunova N.V. Presence of aberrant VH6 domains in anti-interferon-γ autoantibodies in multiple sclerosis. Hum Antibodies. 2013; 22(1-2):31-49.
4. Grigoryeva A.E., Saranina I.V., Tikunova N.V., Safonov A., Timoshenko N., Rebrov A., Ryabchikova E.I. Fine mechanisms of the interaction of silver nanoparticles with the cells of Salmonella typhimurium and Staphylococcus aureus. Biometals. 2013. 26(2), 479-488.
5. Babkin I.V., Tyumentsev A.I., Tikunov A.Yu., Kurilschikov A.M., Ryabchikova E.I., Zhirakovskaya E.V., Netesov S.V., Tikunova N.V. Evolutionary time-scale of primate bocaviruses. Infect. Genet. Evol. 2013. 14, 265-274.
6. Brenner E.V., Brouchkov A.V., Kurilschikov A.M., Griva G.I., Kashuba E., Kashuba V.I., Melefors O., Repin V.E., Melnikov V.P., Vlassov V.V. Draft Genome Sequence of Bacillus cereus Strain F, Isolated from Ancient Permafrost. Genome Announcements. 2013. 1(4), e00561-13.
7. Burkov I.A., Serova I.A., Battulin N.R., Smirnov A.V., Babkin I.V., Andreeva L.E., Dvoryanchikov G.A., Serov O.L. Expression of the human granulocyte–macrophage colony stimulating factor (hGM-CSF) gene under control of the 5′-regulatory sequence of the goat alpha-S1-casein gene with and without a MAR element in transgenic mice. Transgenic Research. 2013. 22(5), 949-964.
8. Tikunova N.V., Dubrovskaya V., Morozova V.V., Yun T., Khlusevich Y.A., Bormotov N., Laman A., Brovko F., Shvalov A., Belanov E. The neutralizing human recombinant antibodies to pathogenic Orthopoxviruses derived from a phage display immune library. Virus Res. 2012. 163(1), 141-150.
9. Babkin I.V., Tikunov A., Zhirakovskaya E.V., Netesov S.V., Tikunova N.V. High evolutionary rate of human astrovirus. Infect. Genet. Evol. 2012. 12(2), 435-442.
10. Romashchenko A.V., Ratushnyak A.S., Zapara T.A., Tkachev S.E., Moshkin M.P. The correlation between tick (Ixodes persulcatus Sch.) questing behaviour and synganglion neuronal responses to odours. Journal of Insect Physiology. 2012. 58(7), 903-910.
11. Babkin I.V., Babkina I.N. A retrospective study of the orthopoxvirus molecular evolution. Infect. Genet. Evol. 2012. 12(8), 1597-1604.
12. Morozkin E.S., Loseva E.M., Morozov I.V., Kurilschikov A.M., Bondar A.A., Rykova E.Y., Vlassov V.V., Laktionov P.P. A comparative study of cell-free apoptotic and genomic DNA using FISH and massive parallel sequencing. Expert Opin. Biol. Ther. 2012. 12(S1), 11-17.
13. Semenov D.V., Baryakin D.N., Brenner E.V., Kurilschikov A.M., Vasiliev G.V., Bryzgalov L.A., Chikova E.D., Richter V.A. Unbiased approach to profile the variety of small non-coding RNA of human blood plasma with massively parallel sequencing technology. Expert Opin. Biol. Ther. 2012. 12(1), 43-51.
14. Brenner E.V., Kurilschikov A.M., Stronin O.V., Fomenko N.V. Whole-Genome Sequencing of Borrelia garinii BgVir, Isolated from Taiga Ticks (Ixodes persulcatus). J. of Bacteriol. 2012. 194(20), 5713.
15. Livanova NN, Tikunova NV, Livanov SG, Fomenko NV. Identification of Ixodes persulcatus and Ixodes pavlovskyi occidentalis (Ixodidae) by the analysis of the gene fragment COXI (cytochrome oxidase subunit I). Parazitologiia. Russian. 2012 Sep-Oct;46(5):340-349.
16. Gabibov A.G., Belogurov A.A. Jr, Lomakin Y.A., Zakharova M.Y., Avakyan M.E., Dubrovskaya V.V., Smirnov I.V., Ivanov A.S., Molnar A.A., Gurtsevitch V.E., Diduk S.V., Smirnova K.V., Avalle B., Sharanova S.N., Tramontano A., Friboulet A., Boyko A.N., Ponomarenko N.A., Tikunova N.V. Combinatorial antibody library from multiple sclerosis patients reveals antibodies that cross-react with myelin basic protein and EBV antigen. FASEB J. 2011. 25, 4211-4221.
17. Rar V.A., Epikhina T.I., Livanova N.N., Panov V.V., Doroschenko E.K., Pukhovskaia N.M., Vysochina N.P., Ivanov L.I. Genetic variability of Anaplasma phagocytophilum in Ixodes persulcatus ticks and small mammals in the Asian part of Russia. Vector-Borne and Zoonotic Diseases. 2011. 11(8), 1013-1021.
18. Rar V., Golovljova I. Anaplasma, Ehrlichia, and «Candidatus Neoehrlichia» bacteria: Pathogenicity, biodiversity, and molecular genetic characteristics, a review. Infect Genet Evol. 2011. 11(8), 1842-1861.

1. Tikunova N.V., Semenov D.V., Babkina I.N., Kuligina E.V., Koval O.A., Fomin A.S., Matveeva V.A., Matveev L.E., Matveev A.L., Richter V.A. Recombinant plasmid DNA pFK2, providing synthesis of the recombinant peptide which is the analog of human kappa-casein, and recombinant peptide – the analog of human kappa-casein fragment, with the apoptotic activity against human tumor cells. Patent RF N.2401307, 2010.
2. Matveev L.E., Matveev A.L., Semenov D.V., Fomin A.S., Kuligina E.V., Matveeva V.A., Tikunova N.V., Babkina I.N., Richter V.A. Strain of hybridous cultured mammalian cells Mus. Musculus producing monoclonal antibodies specific for the peptide possessed apoptotic activity against human tumor cells. Patent RF N.2402605, 2010.

RFBR (Grants of the Russian Foundation for Basic Research)

• N.13-04-00554 «Molecular evolution of small-genome gastroviruses» (2013-2015)
• N.14-04-31549 “Studying of microbioligical simbiotic sistems within Siberian Ixodidae” (2014-2015)
• N.14-04-00567 “The study of parasite-host relations between ixodid ticks, rodents and bacterial and protozoan microorganisms in sympatric areas of three ixodid tick species - Ixodes persulcatus P. Sch., Ixodes trianguliceps Bir. and Ixodes apronophorus P. Sch. in Western Siberia” (2014-2016)

Interdisciplinary integration projects of the Presidium of SB RAS (2012-2014)

• N.7 «Development of scientific bases of technology for long-term storage of agricultural seeds, rare, endangered, wood, and other valuable and promising plant species in the permafrost»
• N.93 «Study of biology, biochemistry and geochemistry of the living and fossil substances and petroleum in the areas of hydrothermal manifestations, evaluation of the role of oil formation in juvenile matter»
• N.94 «Study of biogeotechnological processes associated with extremophilic microorganisms to extract rare and precious elements, biocatalysis and biomedicine»
• N.134 «The implementation of size effects in the original nanobiocomposites with managed complex of magneto-, neutrono-, gamma-, x-ray-, photo-, radiosensitive and highly biospecific properties for a new qualitative level of low- or non-invasive radiology»
• N.135 «Genomics of pathogens carried by ixodes ticks»
• N.139 «Development of bioluminescent reporters for identification of proteins with low and ultralow copy level»
• N.141 «Development of potential therapeutic agents for the treatment of tick-borne encephalitis»

Program of the Presidium of RAS
N.5 “Basic science for medicine”

• N.38 “Development of a new anticytokine preparation on the base of fully human antibody against interleukine 18” (2013-2015)

Grants of the Ministry of Industry and trade of the Russian Federation (2013-2015)

• State contract N.13411.1008799.13.118 «Preclinical studies of the medicine on the basis of chimeric antibodies against tick-borne encephalitis»

• ProteON XPR36 Protein Interaction Array System;
• gel imaging and documentation system Gel Doc™ XR+ with EtBR/SYBR Green BP filter (BioRad, USA);
• chromatography system BioLogic LP (BioRad, USA);
• Gene Pulser Xcell microbial system (BioRad, USA);
• Gene Pulser Xcell eukaryotic system (BioRad, USA);
• spectrophotometr SmartSpec Plus (BioRad, USA); microplate absorbance reader iMark™ (BioRad, USA).