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Laboratory of Molecular Genetics and Congenital Immunity

Contract number
11.G34.31.0052
Time span of the project
2011-2015

As of 30.01.2020

16
Number of staff members
60
scientific publications
11
Objects of intellectual property
General information

Name of the project: Research of cancer. Apoptosis programmed death). Congenital immunity. Inflammation. Obesity and controlling obesity

Strategy for Scientific and Technological Development Priority Level: в


Goals and objectives

Research directions: Congenial immunity, cellular mechanisms, molecular oncology, biomarkers, lymphangiogenesis, systemic and local inflammation, septic shock, molecular targets of action of medications, genetics of autoimmune pathologies, developing test-systems for early diagnostics of ilnesses

Project objective: Targeted search and study of new genes and phenotypes responsible for processes of metabolism, inflammation, apoptosis, induction and progression of tumors and autoimmune illnesses


The practical value of the study

  • We have produced mice lines (mutants and hybrids) that are resistant to septic shock, oncogenesis, and obesity. We have conducted genome sequencing and bioinformatical analysis of anti-inflammation genes in mice lines. Candidate genes responsible for resistivity against TNF have been selected and identified. We have conducted phenotype analysis of homozygous mutant for resistivity against induced tumors.
  • The Laboratory has developed test-system «Diagnostics of inflammation development in vessel walls in patients with lipid exchange disruption», «Early diagnostics of cancer of reproductive organs» and «Pre-clinial diagnostics of conditions based on nonlinear dynamics».
  • We have synthesized a group of new nitrogen-containing compounds with high biological activity. We have shown in vitro and in vivo that reagents possess expressed anti-tumor and anti-inflammation effects. Compounds are viewed as prospective parts of pharmaceuticals.
  • Our research has shown that cells of С57ВL/6 mice (hepatocytes) are highly sensitive to Fas-induced apoptosis by producing higher levels of cFLIPR (short protein isoform) in comparison to hepatocytes of the MSM line (producing the cFLIPL long isoform). cFLIPL binds caspase 8 preventing cell apoptosis.
  • We have determined that transmembrane protein of endoplasmic reticulum STING (Stimulator of Interferon Genes) that is known as a molecular sensor of cytoplasmic DNA that plays an important role in recognizing intracellular pathogens and activation of interferon - (type I) dependent path in cells of myeloid series, has wider functions. STING not only serves as the convergence point of signals sent by other cytosolic sensors/receptors but also is responsible for specific switching simultaneously acting as both a receptor and as an adapter protein. STING can act as a specific signal «hub» whose work is defined by molecular context.

Implemented results of research:

The Laboratory has patented the developed test-systems. The test-systems have passed preliminary approbation at clinical departments of the Medical Institute of the Petrozavodsk State University and being currently prepared for implementation at the Emergency Medical Service Hospital and the Republican Oncological Early Treatment Center in Petrozavodsk

Education and career development:

  • A new master program «Medical and biological sciences» has been introduces.
  • 18 textbooks have been published.
  • We have implemented a career enhancement program for young scientists «Modern methods of research in biomedicine».
  • Electronic courses for school students and teachers of the Republic of Karelia have been developed. The Laboratory curates a class at the Gymnasium No 30 named after D.N. Muzalev in Petrozavodsk.

Organizational and structural changes:

The Institute of High Biomedical Technologies has been created on the basis of the Laboratory. The main goal of the Institute is structuring fundamental and applied research in medicine and biology in accordance with top priority directions of development of Russia in biomedical technologies and international tendencies of science in this field. The other goal is to create conditions for conducting R&D for developing innovative technologies that are ready for implementation in medical practice. The Institute consists of 7 research laboratories, a shared multifunctional center for module education and a certification center. Practical implementation of the Laboratory's achievements is conducted by Nanofarm and BioGen, companies that were created within the project in 2012 and 2013.

Collaborations:

  • Tufts University (USA), First Oncological Research and Consulting Center (Russia): joint research
  • Institute of Bioorganic Chemistry named after M. I. Shemyakin and Yu. A. Ovchinnikov of the Russian Academy of Sciences (Russia): joint research internships of employees
  • Kankormed LLC (Russia): joint scientific events, conferences, seminars

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Moseman A.P., Moseman E.A., Schworer S., Smirnova I., Volkova T., von Andrian U., Poltorak A
Mannose Receptor 1 Mediates Cellular Uptake and Endosomal Delivery of CpG-Motif Containing Oligodeoxynucleotides. The Journal of Immunology 191(11): 5615–5624 (2013).
Schworer S.A., Smirnova I., Kurbatova I., Bagina U., Churova M., Fowler T., Roy A.L., Degterev A., Poltorak A.
Toll-like Receptor-Mediated Downregulation of the Deubiquitinase CYLD Protects Macrophages from Necroptosis in Wild-Derived Mice. The Journal of Biological Chemistry 289(20): 14422–14433 (2014).
Ram D.R., Ilyukha V., Volkova T., Buzdin A., Tai A., Smirnova I., Poltorak A.
Balance between Short and Long Isoforms of cFLIP Regulates Fas-mediated Apoptosis in vivo. Proceedings of the National Academy of Sciences of the United States of America 113(6): 1606–1611 (2016).
Surpris G., Chan J., Thompson M., Ilyukha V., Liu B.C., Atianand M., Sharma S., Volkova T., Smirnova I., Fitzgerald K.A., Poltorak A
Cutting Edge: Novel Tmem173 Allele Reveals Importance of STING N Terminus in Trafficking and Type I IFN Production. The Journal of Immunology 196(2): 547–552 (2016).
Larkin B., Ilyukha V., Sorokin M., Buzdin A., Vannier E., Poltorak A.
Cutting Edge: Activation of STING in T Cells Induces Type I IFN Responses and Cell Death. The Journal of Immunology 199(2): 397–402 (2017).
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