Born: August 12, 1955

• Protein engineering of virus-like particles
• Expression of foreign genes in bacteria and mammalian cells
• Alphavirus gene expression systems
• Alpavirus vectors application for vaccines and gene therapy
• Gene delivary
• Modelling of viral replication
• Stem cells

Languages: Latvian, Russian, English

• University of Latvia (Faculty of Biology), Riga, Latvia, 1977.

Thesis title: „Functional activity of specific RNA fragments from bacteriophage MS2 in protein synthesis initiation system in vitro.” Supervisor: Dr. habil. biol. Elmars Grens.

• Candidate of Science Degree (in former USSR, Ph.D. in Western countries),Institute of Molecular Biology, Moscow, Russia, 1985.

Thesis title: „Expression of the cloned hepatitis B surface antigen gene in E.coli.” Supervisor: Dr. habil. biol. Elmars Grens.

• Dr.biol. Nostrification, Faculty of Biology, University of Latvia (LU), Riga, Latvia, 1993.

Thesis title: „Expression of the cloned hepatitis B surface antigen gene in E. coli.” Supervisor: Dr. habil. biol. Elmars Grens.

• Dr. habil. Biol. Faculty of Biology, University of Latvia (LU), Riga, Latvia, 1997.

Thesis title: „Cloning and expression of viral genomes in prokaryotic and eukaryoti systems”.

Experience

• Junior Research Fellow, Institute of Organic Synthesis, Riga, 1977 - 1981
• Research Fellow, Institute of Organic Synthesis, Riga, 1981 - 1989
• Research Fellow, Institute of Molecular Biology, Riga, 1989 – 1993
• Visiting scientist, Wolfson College, Cambridge, UK, (October 1992- January 1993).
• Visiting scientist, Karolinska Institutet, Department of Biosciences and Nutrition (BioNut), Huddinge, Sweden 1994-1995
• Senior Research Fellow, Biomedical Research and Study Centre, Riga, 1993

• Corresponding Member, the Latvian Academy of Sciences, 2003
• The Latvian Academy of Sciences Award, 1992
• Grindels Medal N100 (award from Grindex, a leading pharmaceutical
  company in the Baltic States) 2006

• Member, Latvian Biochemical Society, 1991 -
• Member, Association of Latvian Scientists, 1990 –

• Master theses of students examined under the main supervision: total number – 5.

• PhD theses of students examined under the main supervision:

1. Inta Vasiljeva, “The coat of RNA phage Q? as a carrier for foreign epitopes”, defended (1998).
2. Anna Zajakina, “Reconstruction of Hepatitis B virus in vivo”, defended (2004).
3. Ekaterina Alexeyeva, “HCV prototype vaccine based on alphaviral recombinant replicons”, defended (2009).
4. Sabine Braun (Humboldt University), “Characterisation of internally deleted Hepatitis B virus core protein variants”, defended (2009).
5. Baiba Niedre-Otomere “Recombinant Semliki Forest virus replicon approach in search of an improved vaccine for Hepatitis B virus: induction of neutralizing antibodies”, submitted (2015).

 Representative Publications

• Borisova GP, Volkova TM (maiden name), Rosenthal G, Berzins VM, Grens EJ. The regulatory region of MS2 phage RNA replicase cistron. IV. Functional activity of specific MS2 RNA fragments in formation of the 70 S initiation complex of protein biosynthesis. - Nucleic Acids Research, 1979; 6:1761-1765.
• Kozlovskaia TM, Dishler AV, Bychko VV, Pumpen PP, Gren EIa. Subjection of tetracycline resistance genes to cat promotor gene in plasmid pBR325. Mol Biol (Mosk). 1981 Sep-Oct;15(5):1158-68.
• Pumpen P.P., Dishler A.V., Kozlovskaya T.M., Bychko V.V., Gren E.J., Rivkina M.B., Grinberg A.P., Kukaine R.A. Cloning of hepatitis B virus DNA in Escherichia coli. - Dokl Akad Nauk SSSR, 1981, vol. 260, N 4, pp. 1022-1024.
• Pumpen P., Kozlovskaya T.M., Borisova G.P., Bichko V.V., Kalis J., Kukaine R.A., Gren E.J. Expression of hepatitis B virus surface antigen gene in E.coli - Gene, 1984, vol. 30, pp. 207-216.
• Kozlovskaya T.M., Pumpen P.P., Borisova G.P., Dishler A.V., Bychko V.V., Kalis J.V., Gren E.J., Kukain R.A. Synthesis of the full amino acid sequence of the surface antigen of the hepatitis B virus in Escherichia coli. - Dokl Akad Nauk SSSR, 1984, vol. 274, N 5, pp. 1250-1253.
• Kozlovskaya T.M., Pumpen P.P. Structure and expression of human hepatitis B virus surface antigen. - Mol. Biol. (Mosk), 1986, vol. 20, N 4, pp. 884-901.
• Kozlovskaya T.M., Pumpen P.P., Dreilina D.E., Tsimanis A.J., Ose V.P., Tsibinogin V.P., Gren E.J. Formation of capsid-like structures as a result of expression of the cloned gene of the envelope protein of the RNA-containing bacteriophage fr. - Dokl Akad Nauk SSSR, 1986, vol. 287, N 2, pp. 452-455.
• Borisova G., Bundule M., Grinstein E., Dreilina D., Dreimane A., Kalis J., Kozlovskaya T., Loseva V., Ose V., Pumpen P., Pushko P., Snikere D., Stankevica E., Tsibinogin V., Gren E.J. Recombinant capsid structures for exposure of protein antigenic epitopes. - Mol.Gen. (Life Sci. Adv.), 1987, vol. 6, pp. 169-174.
• T.Kozlovska, I.Cielens, D.Dreilina, A.Dislers, V.Baumanis, V.Ose, P.Pumpens. Recombinant RNA phage Qb capsid particles synthesized and self-assembled in E.coli. - Gene, 1993, vol. 137, pp. 133-137.
• P.Pushko, T.Kozlovskaya, I.Sominskaya, A.Brede, E.Stankevica, V.Ose, P.Pumpens, E.Grens. Analysis of RNA phage fr coat protein assembly by insertion, deletion and substitution mutagenesis. -Protein Engineering, 1993, vol. 6, pp. 883-891.
• Kozlovska T.M., Cielens I., Vasiljeva I., Strelnikova A, Kazaks A, Dislers A, Dreilina D, Ose V, Gusars I., Pumpens P. RNA phage Qb coat protein as a carrier for foreign epitopes. - Intervirology, 1996, vol. 39, pp. 9-15.
• Kozlovska T.M., Cielens I., Vasiljeva I., Bundule M., Strelnikova A., Kazaks A., Dislers A., Dreilina D., Ose V., Gusars I., Pumpens P. Display vectors. II. Recombinant capsid of RNA bacteriophage Qb as a display moiety. - Proc. Latv.Acad.Sci., 1997, vol. 51, N 1-2, pp. 8-12.
• Vasiljeva I., Kozlovska T., Cielens I., Strelnikova A., Kazaks A., Ose V., Pumpens P. Mosaic Qb coats as a new presentation model. - FEBS Letters, 1998, vol. 431, pp. 7-11.
• Cielens I, Ose V, Petrovskis I, Strelnikova A, Renhofa R, Kozlovska T, Pumpens P. Mutilation of RNA phage Qß virus-like particles: from icosahedrons to rods. - FEBS Letters, 2000, vol. 482, N 3, pp. 261-264
• Forsell K., Xing L., Kozlovska T., Cheng R.H., Garoff H. Membrane proteins organize a symmetrical virus. - EMBO J 2000, vol. 19, pp. 5081-5091.
• A.Zajakina, T.Kozlovska, R.Bruvere, J.Aleksejeva, P.Pumpens, H.Garoff. Translation of hepatitis B virus )HBV) surface proteins from the HBV pregenome and  precore RNAs in Semliki Forest virus driven expression. - J.Gen.Virol., 2004, vol. 85, pp. 3343-3351.
• T.Kozlovska, A.Zajakina, V.Ose, R.Bruvere, J.Aleksejeva, P.Pumpens, H.Garoff.   Synthesis of all Hepatitis B structural proteins in Semliki Forest virus expression system. - Acta Universitatis Latviensis, 2004, vol. 676, pp. 39-51.
• I.Sominskaya, E.Alekseeva, D.Skrastina, V.Mokhonov, E.Starodubova, J.Jansons, M.Levi, A.Prilipov, T.Kozlovska,V.Smirnov, P.Pumpens, M.G.Isaguliants. Signal sequences modulate the immunogenetic performance of human hepatitis C virus E2 gene. - Mol. Immunology, 2006, vol. 43, N 12, pp. 1941-1952.
• Sominskaya I, Alekseeva E, Skrastina D, Mokhonov V, Starodubova E, Jansons J,Levi M, Prilipov A, Kozlovska T, Smirnov V, Pumpens P, Isaguliants MG. Signal sequences modulate the immunogenic performance of human hepatitis C virus E2gene. Mol Immunol. 2006 May;43(12):1941-52. Epub 2006 Jan 25. PubMed PMID:16442623.
• Braun S, Zajakina A, Aleksejeva J, Sharipo A, Bruvere R, Ose V, Pumpens P,Garoff H, Meisel H, Kozlovska T. Proteasomal degradation of core protein variants from chronic hepatitis B patients. J Med Virol. 2007 Sep;79(9):1312-21. PubMed PMID: 1760778
• Zajakina A, Niedre-Otomere B, Alekseeva E, Kozlovska T. Alphaviruses: multiplicity of vectors and their promising application as vaccines and cancer therapy agents. In: Y.Khudyakov (Ed.). Medicinal Protein Engineering. CRC Press, Taylor & Francis Group, Boca Raton London, New York, 2008, pp. 519-550. (book chapter)
• Vasilevska J, Skrastina D, Spunde K, Garoff H, Kozlovska T, Zajakina A. Semliki Forest virus biodistribution in tumor-free and 4T1 mammary tumor-bearing mice: a comparison of transgene delivery by recombinant virus particles and naked RNA replicon. Cancer Gene Ther. 2012 Aug;19(8):579-87. doi: 10.1038/cgt.2012.37. Epub 2012 Jun 22. PubMed PMID: 22722377.
• Niedre-Otomere B, Bogdanova A, Skrastina D, Zajakina A, Bruvere R, Ose V, Gerlich WH, Garoff H, Pumpens P, Glebe D, Kozlovska T. Recombinant Semliki Forest virus vectors encoding hepatitis B virus small surface and pre-S1 antigens induce broadly reactive neutralizing antibodies. J Viral Hepat. 2012 Sep;19(9):664-73. doi: 10.1111/j.1365-2893.2012.01594.x. Epub 2012 May 17. PubMed PMID: 22863271.
• Niedre-Otomere B, Bogdanova A, Bruvere R, Ose V, Gerlich WH, Pumpens P, Glebe D, Kozlovska T. Posttranslational modifications and secretion efficiency of immunogenic hepatitis B virus L protein deletion variants. Virol J. 2013 Feb 25;10:63. doi: 10.1186/1743-422X-10-63. PubMed PMID: 23442390; PubMed Central PMCID: PMC3598826.
• Zajakina A, Bruvere R, Kozlovska T. A Semliki Forest virus expression system as a model for investigating the nuclear import and export of hepatitis B virus nucleocapsid protein. Acta Virol. 2014;58(2):173-9. PubMed PMID: 24957723.
• Bogdanova A, Berzins U, Nikulshin S, Skrastina D, Ezerta A, Legzdina D, Kozlovska T. Characterization of human adipose-derived stem cells cultured in autologous serum after subsequent passaging and long term cryopreservation. J Stem Cells. 2014;9(3):135-48. doi: jsc.2014.9.3.135. PubMed PMID: 25157448.
• Bogdanova-Jatniece A, Berzins U, Kozlovska T. Growth Properties and Pluripotency Marker Expression of Spontaneously Formed Three-dimensional Aggregates of Human Adipose-derived Stem Cells. Int J Stem Cells. 2014Nov;7(2):143-52. doi: 10.15283/ijsc.2014.7.2.143. PubMed PMID: 25473452; PubMed Central PMCID: PMC4249897.
• Zajakina A, Vasilevska J, Kozlovska T, Lundstrom K. Alphaviral vectors for cancer treatment. In: Khudyakov Y., Pumpens P. (editors). Viral Nanotechnology, Chapter 28. CRC Press, Taylor & Francis Group, Boca Raton, London, New York, 2015, July 1, in press. (Book chapter)

 Research Projects:

• National

1. “Self-assembly of virion-like structures in eukaryotic cell cultures”, Latvian Council of Science (1994 - 1996), head of the project.
2. “Construction of recombinant Treponema pallidum surface antigen for diagnostic purposes”, Ministry of Education and Science (1996), participant.
3. “Reconstruction of viral particles in vivo”, Latvian Council of Science (1997 - 2000), head of the project.
4. “Universal Cloning and Expression System by Means of Protease Mutants”, Latvian Council of Science (1997 – 2000), participant
5. “Pathologies associated with the undiagnosable forms of hepatitis B virus”, Latvian Council of Science (1998 - 2001), participant
6. “New age diagnostics of the sexually transmitted diseases”, Latvian Council of Science (1998 - 2001), participant
7. “Reconstruction of viral particles in vivo”, Latvian Council of Science (2000 - 2003), head of the project.
8. “RNA bacteriophage Q? coat mutants with exchanged AB loop”, Ministry of Education and Science (2001), participant.
9. „Molecular mechanisms of variability and persistence of hepatitis virusies”, Latvian Council of Science (2002 - 2005), participant.
10. “Construction of HBV pseudovirions in cultivated eukaryotic cell lines”, Ministry of Education and Science (2003-2008), head of the project.
11. “Optimization of differentiation of human mesenchymal stem cells into in vitro hepatocyte system”, market-oriented research project, project number TOP 07-27, Ministry of Education and Science (2007 - 2009).
12. “Immunomodulative activity of human stem cells in vitro and its safety profile in patients with type 1 diabetes”, project number 09.1283, Latvian Council of Science (2009 - 2013), head of the project
13. “Cell therapy for type 1 diabetes: a novel approach for targeted treatment of insulin-dependency”, project number 10.0014, Latvian Council of Science (2010 - 2014), head of the project.
14. “Elaboration of delivery system for DNA, RNA, protein, peptide, and smal molecule medical preparations”, project number 7, State Research Programme "Development of advanced prevention strategies, treatment, diagnostic tools and methods, biomedical technologies for improving public health" (2010 - 2014), head of the project.
15. “Fine functional structure of hepatitis B core particles: stable expression in eukaryotic cell lines, purification, structural peculiarities, and immunological evaluation”, Latvian Council of Science (2013-2016), head of the Project since 2014.

• EU Funded Projects

1. “Modeling of HBV replication”. Project number VPD1/ERAF/CFLA/05/APK/2.5.1/000018/008, EU Funds Project (2006 - 2008), head of the project.
2. “Artificial virus-like particles (VLP, virus-like particles) as the new vaccines, gene therapies and diagnostic tools platform”, Project number VPD1/ERAF/CFLA/05/APK/2.5.1/000019/009, EU Funds Project (2006 - 2008), participant.
3. “Novel model of HBV infection and a technology for antiviral agent evaluation”, project number 2010/0233/2DP/2.1`.1.1.0/10/APIA/VIAA/075, project was carried out within the European Regional Development Fund (ERDF) activity "Support for science and research" (2011 - 2013), head of the project.

• International Projects

1. “Recombinant viral particulate proteins as tools for new vaccines and diagnostics”, INCO RTD project ERB-CIPA-CT-0187, participant
2. “Development of a novel episomal vector based on papillomaviral replicons and its use in gene therapy”, INCO RTD project , participant
3. “Particulate carriers in the development of AIDS vaccines and therapy”. EC Concerted Research Programme EVA, participant
4. “Hepatitis B virus assembly, structure and entry into new host cells”, KIRT programme, contractor.
5. “Expression, purification and structure determination of ENA-78”, KIRT programme, contractor.
6. “Research and development of immunological methods. Production of ELISA tests for the diagnosis of hepatitis B”, NATO Science for Stability, participant.
7. “Expression, purification and structure determination of ENA-78.” The Royal Swedish Academy of Sciences, Cooperation between Sweden and the former Soviet Union, participant.
8. “DNA vaccination against hepatitis C virus infection”, INCO-Copernicus RTD project, IC 15980313, contractor.
9. “Combined immune and gene therapy for chronic viral hepatitis”, QoL RTD project, QLK2-Ct-2000-01476, participant.
10. “Artificial chimeric proteins as diagnostic, vaccine, and gene therapy carriers” QoL project, Marie Curie Training Site, QLK2-1999-51115, participant.
11. “Construction of HBV/HCV replication models for the design and screening of putative antiviral drugs. Taiho Project”, (2002-2004), participant.
12. “Rational design and comparative evaluation of novel genetic vaccines”, Framework 6 Integrated Project "COMPUVAC (2005-2008), participant.
13. “Analysing the intracytosolic transport of chimeric hepatitis B virus capsids exposing domains of the HIV integrase” OSMOSE (2007-2008), participant.

Patents

• SU

1. (SU 1744110 A1) Limited Patent. Recombinant Plasmid Dna Pfrbls F6, Encoding Fused Protein Of Bacteriophage For Envelope And Envelope Protein Of Cattle Leukosis Virus Gp51, Method Of Its Construction, And Strain Of Bacteria Escherichia Coli. Applicant: Inst Organicheskogo Sinteza Ak, Otdel Meditsiny Univ Gumboldta. Rajner Ulrikh, Khelga Siakkou, Korteliya Plattser, Zinaida Rozental, Alfred Rozental Khans, Kozlovskaya Tatyana M, Sominskaya Irina V, Drejlinya Dzidra E, Ozols Yuris A, Pushko Petr M, Pumpen Pavel P, Gren Elmar Ya. Publication: Jun 30, 1992 SU_1744110_A1; Application: Aug 10, 1989 SU_4728855_A; Priority: Aug 10, 1989 SU_4728855_A.
2. (SU 1751208 A1) Limited Patent. Recombinant Plasmid Dna Pfr Blv-f6, Encoding Bacteriophage fr Envelope Protein And Protein gp51 Of Cattle Leukosis Virus, Method Of Its Construction And Strain Of Bacteria Escherichia Coli - A Producer Of Bacteriophage fr Envelope Protein And Protein gp51 Of Cattle Leukosis Virus. Applicant: Inst Organicheskogo Sinteza Ak, Otdel Meditsiny Sharite Univ G. Rajner Ulrikh, Khelga Siakkou, Korneliya Plattser, Zinaida Rozental, Alfred Rozental Khans, Kozlovskaya Tatyana M, Sominskaya Irina V, Drejlinya Dzidra E, Brede Artis Ya, Ozols Yuris A, Pushko Petr M, Pumpen Pavel P, Gren Elmar Ya. Publication: Jul 30, 1992 SU_1751208_A1; Application: Aug 10, 1989 SU_4745577_A; Priority: Aug 10, 1989 SU_4745577_A.

• DBR

1. Ulrich Rainer, Siakkou Helga, Platzer Cornelia, Rosenthal Sinaida, Rosenthal Hans-Alfred, Kozlovskaja Tatjana, Sominskaja Irina, Dreilina Dzidra, Brede Artis, Ozols Juris, Pushko Peter, Pumpen Paul, Gren Elmar. Verfahren zur Herstellung des rekombinanten Proteins frCP-BLVgp51(56-103), das eine Fusion aus Coatprotein des Phagen fr und dem Hullproteinabschnitt gp51(56-103) des bovinen Leukamievirus darstellt. Ausschließungspatent DD 286 816 A5, Bundesrepublik Deutschland. 10.08.89. Publ. 07.02.91.
2. Ulrich Rainer, Siakkou Helga, Platzer Cornelia, Rosenthal Sinaida, Rosenthal Hans-Alfred, Kozlovskaja Tatjana, Sominskaja Irina, Dreilina Dzidra, Ozols Juris, Pushko Peter, Pumpen Paul, Gren Elmar. Verfahren zur Herstellung des rekombinanten Proteins frCP-BLVgp51sh, das eine Fusion aus Coatprotein des Phagen fr und dem Hullproteinabschnitt gp51sh des bovinen Leukamievirus darstellt. Ausschließungspatent DD 286 817 A5, Bundesrepublik Deutschland. 10.08.89. Publ. 07.02.91.
3. Ulrich Rainer, Mohring Regina, Pushko Peter, Kozlovskaja Tatjana, Dischler Andris, Dreilinja Dzidra, Ozols Juris, Pumpen Paul. . Verfahren zur Herstellung der rekombinanten Kapsidstruktur frCP-HIVenv(474-759), das eine Fusion aus Coatprotein des Phagen-fr und dem Hüllproteinabschnitt des humanen Immunodefizienzvirus 1 darstellt. Ausschließungspatent DD 300 652 A5 (1992) Bundesrepublik Deutschland.
4. Sominskaja Irina, Pushko Peter, Kozlovskaja Tatjana, Meisel Helga, Jantschak Joachim, Pumpen Paul, Ozols Juris, Dreilinja Dzidra, Ulrich Rainer. Verfahren Zur Herstellung Des Rekombinanten Proteins Frcp-pres2+adw Das Eine Fusion Aus Coatprotein Des Phagen Fr Und Dem Pres2-bereich Des Hepatitis B-virus, Subtyp Adw, Darstellt. Applicant: Univ Berlin Humboldt. Publication: Aug 14, 1991 DD_292928_A5; Application: Mar 23, 1990 DD_33899790_A; Priority: Mar 23, 1990 DD_33899790_A.

Last update 9.06.2015