WoS Research ID: B-2617-2012
Scopus ID: 7003708619
РИНЦ ID: 88757
The major direction of the Laboratory’s research is structural and functional analysis of human genome at molecular, biochemical and cellular levels.
WoS Research ID: B-2027-2016
Scopus ID: 36499477600
РИНЦ ID: 600252
WoS Research ID: B-2617-2012
Scopus ID: 7003708619
РИНЦ ID: 88757
WoS Research ID: O-4486-2017
РИНЦ ID: 104586
WoS Research ID: E-3220-2015
Scopus ID: 7004664097
РИНЦ ID: 319793
WoS Research ID: H-8201-2017
Scopus ID: 24833392800
РИНЦ ID: 596509
РИНЦ ID: 603880
WoS Research ID: B-3251-2016
Scopus ID: 6602363686
РИНЦ ID: 87949
The studies are conducted within the following RSW (research scientific work) topics:
I. Molecular mechanism of action of human cell-free DNA fragments on the functionality of different types of cells
The laboratory is currently engaged in studying the characteristics of cell-free DNA in health and various diseases (autoimmune, inflammatory, neurodegenerative, psychiatrical), critical states, stress, and pregnancy. It was shown that during pathology, such characteristics of cell-free DNA as blood plasma content, fragment sizes, fraction of GC-rich motifs, degree of oxidative modification of the bases substantially changes.
Biological activity of cell-free DNA is also explored. Simulating in vitro the processes, which occur after an exposure to cell-free DNA, makes it possible to study the changes of gene expression in pathology and to reveal cell signaling pathways invlolved in the pathogenesis. An exposure to cell-free DNA was shown to result in changes of the gene expression profile of signaling pathways, which control DNA repair, adaptive response, and antioxidant activity in the cell.
The laboratory team discovered a molecular mechanism, by dint of which the cell population (or the body) reacts to the oxidative stress. The main 'player' in the signaling cascade under study is oxidized and/or CpG-enriched cell-free DNA. Cell-free DNA have the property of penetrating the cell structures located close to the nuclear membrane, and inducing a sharp increase in the synthesis of reactive oxygen species (ROS) in mitochondria. The 'burst' of ROS synthesis close to the nucleus induces oxidation and break formation in nuclear DNA, as well as development of adaptive response in the cell population, which favors survival of cells, including cells with damaged DNA. This process can result in genome rearrangements and mutagenesis. The laboratory continues to study molecular mechanisms of the interaction between cell-free DNA and cells of differentn-types, and to search for receptors, through which cell-free DNA affects the cells.
II. Studying the effect of nanomaterials on the functional activity of human genome
The laboratory team performs studying the influence of novel water-soluble fullerene derivates [C60] and/or [C70] on the functional activity of human genome in cell cultures. A mechanism of antioxidant fullerene activity was for the first time described. It was shown, that fullerenes, which actively inhibit reactive oxygen species, nonetheless, induce oxidative stress in human cells. Fullerenes were demonstrated to be able to alter the lineage of human stem cells.
The following researches are currently conducted in Laboratory of Molecular Biology, supported with the following RFBR (Russian Foundation of Basic Research) grants:
1. "Cell-free DNA as a signaling molecule during an exposure to low doses of radiation. A study of the molecular mechanisms of action of low doses of radiation on human stem cells, – an adaptive response or nuclear DNA damage?" (16-04-01099)
The project is aimed to the examination of the molecular mechanisms of action of low doses of radiation on human stem cells. The project plans to justify a hypothesis of action of low doses of radiation though a extracellular mediator of the cell-to-cell signal transmission – fragments of GC-enriched oxidized cell-free DNA.
2. "A study of the role of cell-free DNA and disruptions of transcriptome of the signaling pathways in schizophrenia pathogenesis" (17-29-06017)
The project is aimed to the examination of the properties of cfDNA circulating in schizophrenia patients and to the clarification of the role of the circulating cell-free DNA in the alteration of the genome transcriptional activity profile in schizophrenia patients.
3. "Disruptions of transcriptome of signaling cascades in autism. A study of the role of cell-free DNA in autism pathogenesis" (17-04-01587)
The project is aimed to revealing cell signaling cascades involved in the development of autism. During implementation of the project, studying the role of cell-free DNA in the progression of autism and identifying potential target genes of the signaling pathways, which are engaged in the response of the autism patient's cell for oxidative stress the cfDNA fragments trigger, are planned.
4. "Examination of the role of mitochondria in the control of apoptosis process that results from an exposure to ionizing radiation in low and moderate doses" (18-34-00878)
The project is aimed to analysis of the role of mitochondria in the control of apoptosis process that results from an exposure to ionizing radiation in low and moderate doses and studying the molecular mechanisms that mediate the development of the adaptive response.
In 2018, the Laboratory of Molecular Biology obtained the RSF (Russian Science Foundation) grant "The role of ribosomal genes in the etiology and nosogenesis of schizophrenia. Prognostic value of the characteristics of the patient's ribosomal gene complex in the response for schizophrenia therapy" (18-15-00437)
During implementation of the project, the structural-functional organization of ribosomal genes (rDNA) of schizophrenia patients will be explored and compared to ribosomal genes of mentally healthy controls with determining variability of the total number of rDNA copies per genome, methylation levels of different rDNA regions, rDNA damage degree, and rRNA gene expression (amount of rRNA). The characteristics of ribosomal gene complex will be put together with clinical forms of schizophrenia, and with the efficiency of the patient's response for treatment. In order to describe the common characteristics of schizophrenia genome, examination of variability of three repeats, – mitochondrial DNA (a marker of mitochondria abundance), telomere repeat (a marker of the oxidative stress degree and aging index) and satellite III(1q12) (evaluation of chromosomal instability) is planned. On primary cells and cell cultures derived from cases and controls, as well as rat brain neurons, the effect of a number of antipsychotics administered in domestic psychiatry upon the characteristics of the ribosomal gene complex and upon the variability of the other three above-mentioned genomic repeats will be studied. A possibility to reduce the transcriptional activity of ribosomal genes in the patient's cell using novel domestic compounds, which induce selective methylation of ribosomal DNA, will be studied.
The Laboratory of Molecular Biology conducts a research within the frameworks of Project supported by Research Program of the Presidium of RAS (Russian Academy of Sciences) "Fundamental Researches for Biomedical Technologies" for years 2018 – 2020: "A study of the role of GC-rich sequences of cell-free DNA in cell-to-cell interaction during the development of adaptive response in cancer cells; Designing medicinal agents that affect the cell-to-cell interaction during the therapy of oncological diseases."
The project has scheduled a study of possibility to reduce the tolerance of the malignant tumor cells to the applied therapy using genome editing and small interfering RNAs.
List of most topical published articles of the Laboratory of Molecular Biology for the recent five years: