Valentina Orlova
Doctor of Biological Sciences
Associate Professor,
department of System Ecology
Honesty in scientific research.
1967
Graduated from the Faculty of Biology of Moscow State University and was enrolled in a postgraduate programme of the Institute of Biological and Medical Chemistry of the Russian Academy of Medical Sciences.
1971
Completed postgraduate studies, defended the PhD thesis entitled “Hormonal Regulation of Glycogens in Rats”.
1971-1976
Worked at the Institute of Biomedical Chemistry of the Russian Academy of Medical Sciences as a Junior Research Fellow.
1976-1985
Senior Research Fellow in All Soviet Union Research Institute of Biosynthesis of Protein Substances “VVNIIsyntezbelok”.
1985-1992
Senior Research Scientist, then Chief Research Fellow of the PFUR Institute of Biomedical Research.
1989
Defended Doctor’s thesis in Biochemistry and Microbiology entitled “Physiology and biochemistry of hybrids of yeast – producers of food and feed protein”.
1992-present
Professor of the RUDN University Department of Systems Ecology.
1997-present
Member of the Russian Biochemical Society.
1998
Awarded the Gold Medal of the International Exhibition of Innovations “Euvreca-98” (Brussels, Belgium) for unlocking the mechanism of action of a nucleotide preparation and the way of obtaining it.
1998-present
Member of FEBS (Federation of European Biochemical Societies).
2000
Awarded the VVC Silver Medal for clinical testing of nucleotide preparation.
2001
Awarded the Silver Medal of the Russian Health Ministry for the contribution to national health.
2003
Awarded the First-Degree Diploma at the exhibition competition «High-efficiency Food Technologies, Methods and Means for Their Implementation» for drug formulation of the nucleotide preparation VITANAM.
2003-present
Member of FASEB (Federation of American Societies for Experimental Biology).
2007
Member of the Russian Society of Biotechnologists.
2011
Awarded the Diploma of “Innovative projects and public health” (Dubna, Russia) for the drug formulation VITANAM.
Teaching
Valentina S. Orlova delivers lectures for bachelor students in Ecology and Nature Management and Energy and Resource-saving Processes in Chemical Technology, Petrochemistry and Biotechnology in the following disciplines:
- Biology of a cell;
- Applied ecology.
She teaches original courses for bachelor students in Energy and Resource-saving Processes in Chemical Technology, Petrochemistry and Biotechnology in the following disciplines:
- Ecobiotechnology;
- Basic Biochemistry
Science
- Valentina S. Orlova developed the technology of recycling of agricultural waste and the waste containing cellulose aimed at receiving target products (feed protein and glucose). The technology has been patented, currently the technology is under implementation at the Arkhangelsk pulp and paper plant.
- A number of medicinal products have been developed, in particular a complex nucleotide preparation from the yeast Saccharomyces cerevisiae (international patent). The preparation was registered by the Health Ministry of the Russian Federation as an immunostimulatory drug product for the treatment of acute respiratory viral infections of adults and children aged 6 and above, seasonal prevention of acute respiratory viral infections and complex therapy of type 2 diabetes mellitus.
- Innovative technology of complex processing of active sludge of treatment plants into high-quality, environmentally friendly, granulated organic fertilizer has been developed. Under the technology active sludge undergoes short-term pre-treatment to sterilize feedstock, inactivate toxic substances and antibiotics.
- One of the founders of the engineering and manufacturing centre SANTEHPROM-ECOBIOTEH created to implement modern environmental solutions developed by the scientific community, firstly, issues of waste disposal by means of creating multi-purpose processing lines and production modules for the disposal of agricultural, wood-working, milling and food-industry waste and production of high-demanded goods on their basis (fertilizers, feeding stuff, glucose, etc.)
- author/co-author of 8 patents, including 3 international patents:
- Method of obtaining a nucleotide preparation from the yeast Saccharomyces cerevisiae, 1998;
- Change in carbohydrate metabolism when growing microorganisms on the non-carbohydrate sources of carbon feed, 1998;
- Method of obtaining a highly-efficient strain of yeast with maximum ATP (adenosine triphosphate), 1999.
Areas of expertise
- Cancerous tumor development mechanism and early diagnosis of cancer.
- Study of type 2 diabetes development and mechanisms of its alleviation.
Research into genetic and biochemical bases of regulation of cell death which results in new methods of cancer detection and in future their treatment; development of new preparations for the treatment of Parkinson’s disease; prevention of cardiovascular diseases of spacemen during space flights.
The activity of telomerase catalytic subunit hTERT (human telomerase reverse transcriptase) can be regulated by alternative splicing of its mRNA. The mechanism of hTERT splicing is not understood in detail. Apoptotic endonuclease EndoG is known to participate in this process. In the present work, the intracellular colocalization and mRNA levels of EndoG and hTERT splice-variants in normal and apoptotic cancer cells were studied. We found that the development of apoptosis increased the expression of EndoG and changed the ratio of hTERT splice-variants, which decreased the telomerase activity in the cells. The development of apoptosis was accompanied by changes in the amount of mRNA and in the localization of EndoG and hTERT splice-variants in the cytoplasm, nuclei, and mitochondria of the cells. The suppression of EndoG expression using RNA interference prevented induction of the α+β–splice-variant of hTERT and inhibition of the telomerase activity. A high degree of the intracellular colocalization of EndoG and hTERT was shown. The changes in the expression and localization of EndoG corresponded with changes in the amount and localization of hTERT splice-variants. These data confirm the participation of EndoG in the alternative splicing of mRNA of the telomerase catalytic subunit and in regulation of the telomerase activity.
The diversity of Lb. rhamnosus and Lb. fermentum strains isolated from feces, saliva, and the vaginal cavity of 18–22-year-old healthy women residing in central regions of the Russian Federation has been characterized. The results obtained using multilocus sequence typing were identical to those obtained with the analysis of genetic and genomic polymorphism in TA systems. Different as well as identical Lb. rhamnosus and Lb. fermentum sequence types (ST) were isolated from various parts of the body of the same person. Identical ST were also isolated from different women, suggesting that such strains belong to a common pool of strains circulating among the population members. Our results demonstrate that TAs are suitable for characterizing intra-specific diversity of Lb. rhamnosus and Lb. fermentum strains. The advantage of using polymorphisms in TA systems for genotyping is based on the weak number of genes used, and consequently, less time is required for the analysis.
Alternative splicing of telomerase catalytic subunit hTERT pre-mRNA (human Telomerase Reverse Transcriptase) regulates telomerase activity. Increased expression of non-active splice variant hTERT results in inhibition of telomerase. Apoptotic endonuclease EndoG is known to participate in hTERT alternative splicing. Expression of EndoG can be induced in response to DNA damages. The aim of this study was to determine the ability of a DNA-damaging compound, cisplatin, to induce EndoG and its influence on alternative splicing of hTERT and telomerase activity in human CD4⁺ Т lymphocytes. Overexpression of EndoG in CD4⁺ T cells downregulated expression of the active full-length hTERT variant and upregulated its non-active spliced variant. Reduction of full-length hTERT caused downregulation of telomerase activity, shortening of telomeres length during cell divisions, converting cells to the replicative senescence state, activation of apoptosis and finally cell death. Few cells survived and underwent malignant transformation. Transformed cells have increased telomerase activity and proliferative potential compare to initial CD4⁺ T cells. These cells have phenotype of T lymphoblastic leukemic cells and are able to form tumors and cause death in experimental mice.
Gamma-amino butyric acid (GABA) is an active biogenic substance synthesized in plants, fungi, vertebrate animals and bacteria. Lactic acid bacteria are considered the main producers of GABA among bacteria. GABA-producing lactobacilli are isolated from food products such as cheese, yogurt, sourdough, etc. and are the source of bioactive properties assigned to those foods. The ability of human-derived lactobacilli and bifidobacteria to synthesize GABA remains poorly characterized. In this paper, we screened our collection of 135 human-derived Lactobacillus and Bifidobacterium strains for their ability to produce GABA from its precursor monosodium glutamate. Fifty eight strains were able to produce GABA. The most efficient GABA-producers were Bificobacterium strains (up to 6 g/L). Time profiles of cell growth and GABA production as well as the influence of pyridoxal phosphate on GABA production were studied for L. plantarum 90sk, L. brevis 15f, B. adolescentis 150 and B. angulatum GT102. DNA of these strains was sequenced; the gadB and gadC genes were identified. The presence of these genes was analyzed in 14 metagenomes of healthy individuals. The genes were found in the following genera of bacteria: Bacteroidetes (Bacteroides, Parabacteroides, Alistipes, Odoribacter, Prevotella), Proteobacterium (Esherichia), Firmicutes (Enterococcus), Actinobacteria (Bifidobacterium). These data indicate that gad genes as well as the ability to produce GABA are widely distributed among lactobacilli and bifidobacteria (mainly in L. plantarum, L. brevis, B. adolescentis, B. angulatum, B. dentium) and other gut-derived bacterial species. Perhaps, GABA is involved in the interaction of gut microbiota with the macroorganism and the ability to synthesize GABA may be an important feature in the selection of bacterial strains – psychobiotics.
Telomerase activity is known to be regulated by alternative splicing of its catalytic subunit hTERT (human Telomerase Reverse Transcriptase) mRNA. Induction of non-active spliced hTERT leads to inhibition of telomerase activity. However, very little is known about the mechanism of hTERT mRNA alternative splicing. The aim of this study was to determine the role of apoptotic endonuclease EndoG in alternative splicing of hTERT and telomerase activity. Strong correlation was found between expression of EndoG and hTERT splice-variants in 12 colon cancer cell lines. Overexpression of EndoG in СаСо-2 cells downregulated the expression of active full-length hTERT variant and upregulated non-active spliced variant. Reduction of full-length hTERT caused downregulation of telomerase activity, dramatically shortening of telomeres length during cell divisions, converting cells to the replicative senescence state, activation of apoptosis and finally cell death. These data indicated the participation of EndoG in alternative splicing of mRNA of telomerase catalytic subunit, regulation of telomerase activity and cell fate.
Evaluation of the dose-dependent effects of heavy metals on the viability of a human neuroblastoma SH-SY5Y cell culture showed that 50% cell death was observed in the presence of 5 × 10–4 М lead, 5 × 10–6 М cadmium, 5 × 10–5 М cobalt, and 10–5 М molybdenum. The presence of these metals led to an increase in the level of reactive oxygen species (ROS) (from 39% to 74% in the cases of lead and cobalt, respectively). We revealed a cytoprotective effect against toxic heavy metals (HMs) of a new synthetic compound, (S)-6-hydroxy-2,5,7,8-tetramethylchroman-2-carbonyl-β-alanyl-L-hystidine. This compound is a combination of carnosine with a water-soluble vitamin E analog, trolox (S-trolox–carnosine, S-TC). S-TC efficiently increased the cell viability in the presence of any of the studied metals, which correlated with a decrease in the proportion of necrotic cells and with efficient inhibition of ROS formation. Trolox also had a large cytoprotective effect under toxic conditions caused by lead, cadmium, and cobalt. The protective activity of carnosine under these conditions was significantly lower than the effects of trolox or trolox–carnosine. In general, these results revealed the greater cytoprotective effect of S-trolox–carnosine in the presence of heavy metals as compared to its precursors, trolox and carnosine.