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Invited researcher Yuriy Vasilyevich Kotelevtsev
Contract number
11.G34.31.0032
Time span of the project
2010-2012

As of 30.01.2020

32
Number of staff members
8
scientific publications
General information

Name of the project: Targeted stem cell genome modification as a platform for searching for new pharmaceuticals

Strategy for Scientific and Technological Development Priority Level: в


Goals and objectives

Research directions: Producing new knockout mouse lines immune to atherosclerosis, methods of stem cell genome modification and in vivo investigation of processes occurring in vessel walls, methods of of two-photon laser scanning microscopy; creating «cosmetics» containing hyaluronan for vessels

Project objective:

  • Research of possible ways for correction of atherosclerosis
  • Search for new targets for medications using targeted genome modification


The practical value of the study

  • We have created a bank of E.Coli strains and plasma vectors carrying genetic structures necessary for targeted genome modification.
  • Our researchers have prepared lines of the 129Ola embryo stem cells and tested methods of their modification and cloning.
  • Optical methods for research of glycocalyx. Data has been obtained on the key role of vessel endothelium glycocalyx in development of atherosclerosis.
  • We have refined the method of implanting telemetric sensors for ECG.
  • We have refined the method of hypertrophy of vessel walls in response to mechanical damage of endothelium.
  • We have created in vitro and in vivo models that allow us to analyze drugs and search for new targets for treatment of the Alzheimer's disease.
  • Our researchers have refined a method of immunoferment detection of syndekane in mouse blood plasma. A comparison of a commercial set for determining human syndekane with antibodies to syndekane-1 of mice produced at our Laboratory. We have shown high specificity of the method that allows to determine amount of syndekane diluted in plasma. We have also shown that in the process of development of atherosclerosis in mice of the ApoE line concentration of syndekane increases. We have drawn blood samples from mice with different stages of atheroma development.

Education and career development: 6 masters dissertations have been defended

Collaborations:

University of Edinburgh (United Kingdom), A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences (Russia): joint research

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Kirkby N.S., Duthie K.M., Miller E., Kotelevtsev Y.V., Bagnall A.J., Webb D.J. and Hadoke P. W.F.
Non-endothelial Cell Endothelin-B Receptors Limit Neointima Formation Following Vascular Injury. Cardiovascular Research 95(1): 19–28 (2012).
Deuchar G.A., Patrick M.D., Hadoke W.F., Brownstein D.G., Webb D.J., Mullins J.J., K. Chapman, Seckl J. R. and Kotelevtsev Y.V.
11-Hydroxysteroid Dehydrogenase Type 2 Deficiency Accelerates Atherogenesis and Causes Proinflammatory Changes in the Endothelium in Apoe / Mice. Endocrinology 152(1): 236–246 (2011).
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