INSTITUTE OF CYTOLOGY OF THE RUSSIAN ACADEMY OF SCIENCES

Group of ion channel modeling
Group Chief

Olga OSTROUMOVA

Ph.D., D.Sci. (Biol.)

phone: +7 (812) 297-24-60
e-mail: ostroumova@incras.ru
 



The group was founded in 1997 by Prof. Ludmila Schagina


Scientific Staff

Valery V. Malev
Ph.D., D.Sci. (Chem.)
valerymalev@gmail.com

Svetlana S. Efimova
Ph.D. (Biol.)
ssefimova@mail.ru

Evgeny G. Chulkov
Ph.D. (Biol.)
echulkov@incras.ru

Anastasiia S. Zakharova
Ph.D. student
zakharovaaa@incras.ru


Research focus:

The main focus is molecular mechanisms of the functioning of lipid membranes and reconstituted ion channels. To perform the research, model lipid membranes, planar lipid bilayers and liposomes, are used. The methods include registration of currents flowing through planar lipid bilayers under voltage clamp conditions, differential scanning microcalorimetry of lipid suspensions, confocal fluorescence microscopy of lateral heterogeneity of liposomal membranes, and fluorimetry of dye leakage from lipid vesicles. The objects of study are various pore-forming antibiotics and toxins: antifungal and antimicrobial lipopeptides of bacterial origin, antifungal polyene macrolide antibiotics, insect antimicrobial peptides, alpha-toxin of Staphylococcus aureus, amyloidogenic peptides associated with human neurodegenerative diseases. The physicochemical properties of the membranes are changed by small amphiphilic molecules so-called membrane modifiers. Among the modifiers used, special attention is paid to low-toxic compounds of plant origin, flavonoids and alkaloids, as well as compounds with pronounced pharmacological activity, in particular, thyroid hormones and local anesthetics. The figure shows a diagram illustrating the effect of local anesthetic tetracaine on ion channels formed by amphotericin, nystatin, syringomycin E, magainin and melittin. The approach used opens up broad perspectives for obtaining fundamental knowledge about the structure and functions of ion channels and drug development.

The work of the team is constantly supported by grants from the Russian Science Foundation, the Russian Foundation for Basic Research, the Program of the President of the Russian Federation, grants from the Government of St. Petersburg.


Selected publications

  1. Ostroumova O.S., Chulkov E.G., Stepanenko O.V., Schagina L.V. 2014. Effect of flavonoids on the phase separation in giant unilamellar vesicles formed from binary lipid mixtures. Chem. Phys. Lipids. 178:77-83. doi: 10.1016/j.chemphyslip.2013.12.005.
  2. Ostroumova O.S., Efimova S.S., Mikhailova E.V., Schagina L.V. 2014. The interaction of dipole modifiers with amphotericin-ergosterol complexes. Effects of phospholipid and sphingolipid membrane composition. Eur. Biophys. J. 43(4-5):207-215. doi: 10.1007/s00249-014-0946-0.
  3. Efimova S.S., Schagina L.V., Ostroumova O.S. 2014. —hannel forming activity of cecropins in lipid bilayers. Effect of agents modifying the membrane dipole potential. Langmuir. 30(26):7884-7892. doi: 10.1021/la501549v.
  4. Efimova S.S., Schagina L.V., Ostroumova O.S. 2014. The influence of halogen derivatives of thyronine and fluorescein on the dipole potential of phospholipid membranes. J. Membr. Biol. 247(8):739-745. doi: 10.1007/s00232-014-9703-7.
  5. Chulkov E.G., Efimova S.S., Schagina L.V., Ostroumova O.S. 2014. Direct visualization of solid ordered domains induced by polyene antibiotics in giant unilamellar vesicles. Chem. Phys. Lipids. 183:204-207. doi: 10.1016/j.chemphyslip.2014.07.008.
  6. Efimova S.S., Schagina L.V., Ostroumova O.S. 2014. Investigation of channel-forming activity of polyene macrolide antibiotics in planar lipid bilayers in the presence of dipole modifiers. Acta Naturae. 6 (4): 67-79.
  7. Chulkov E.G., Schagina L.V., Ostroumova O.S. 2015. Membrane dipole modifiers modulate single-length nystatin channels via reducing elastic stress in the vicinity of the lipid mouth of a pore. Biochim. Biophys. Acta. 1848(1):192-199. doi: 10.1016/j.bbamem.2014.09.004.
  8. Efimova S.S., Ostroumova O.S. 2015. Modifiers of the dipole potential of lipid bilayers. Acta Naturae. 7 (4): 70-79.
  9. Ostroumova O.S., Efimova S.S., Malev V.V. 2015. Modifiers of membrane dipole potentials as tools for investigating ion channel formation and functioning. Int. Rev. Cell Mol. Biol. 315:245-297.
  10. Efimova S.S., Malev V.V., Ostroumova O.S. 2016. Effects of dipole potential modifiers on heterogenic lipid bilayers. J. Membr. Biol. 249(1-2):97-106. doi: 10.1007/s00232-015-9852-3.
  11. Efimova S.S., Zakharova A.A., Schagina L.V., Ostroumova O.S. 2016. Two types of syringomycin E channels in sphingomyelin-containing bilayers. Eur. Biophys. J. 45(1):91-98. doi: 10.1007/s00249-015-1101-2.
  12. Abkin S.V., Ostroumova O.S., Komarova E.Y., Meshalkina D.A., Shevtsov M.A., Margulis B.A., Guzhova I.V. 2016. Phloretin increases the anti-tumor efficacy of intratumorally delivered heat-shock protein 70 kDa (HSP70) in a murine model of melanoma. Cancer Immun. Immunother. 65 (1): 83-92. doi: 10.1007/s00262-015-1778-1.
  13. Chulkov E.G., Ostroumova O.S. 2016. Phloretin modulates the rate of channel formation by polyenes. Biochim. Biophys. Acta. 1858 (2): 289-294. doi: 10.1016/j.bbamem.2015.12.004.
  14. Efimova S.S., Zakharova A.A., Schagina L.V., Ostroumova O.S. 2016. Local anesthetics affect gramicidin A channels via membrane electrostatic potentials. J. Membr. Biol. 249(1):781-787. doi: 10.1007/s00232-016-9926-x.
  15. Efimova S.S., Ostroumova O.S. 2017. Dipole modifiers are regulators of the lateral heterogeneity of lipid membranes. Acta Naturae. 9 (2): 67-74.
  16. Efimova S.S., Tevyashova A.N., Olsufyeva E.N., Bykov E.E., Ostroumova O.S. 2017. Pore-forming activity of new conjugate antibiotics based on amphotericin B. PLoS One. 12(11):e0188573. doi: 10.1371/journal.pone.0188573.
  17. Efimova S.S., Zakharova A.A., Ismagilov A.A., Schagina L.V., Malev V.V., Bashkirov P.V., Ostroumova O.S. 2018. Lipid-mediated regulation of pore-forming activity of syringomycin E by thyroid hormones and xanthene dyes. Biochim. Biophys. Acta. 1860(3):691-699. doi: 10.1016/j.bbamem.2017.12.010.
  18. Efimova S.S., Chulkov E.G., Ostroumova O.S. 2018. Lipid-mediated mode of action of local anesthetics on lipid pores induced by polyenes, peptides and lipopeptides. Colloids Surf B Biointerfaces. 166:1-8. doi: 10.1016/j.colsurfb.2018.02.051.
  19. Efimova S.S., Zakharova A.A., Medvedev R.Ya., Ostroumova O.S. 2018. Ion channels induced by antimicrobial agents in model lipid membranes are modulated by plant polyphenols through surrounding lipid media. J. Membr. Biol. 251(4):551-562. doi: 10.1007/s00232-018-0031-1.
  20. Zakharova A.A., Efimova S.S., Schagina L.V., Malev V.V., Ostroumova O.S. 2018. Blocking ion channels induced by antifungal lipopeptide syringomycin E with amide-linked local anesthetics. Sci. Rep. 8(1):11543. doi: 10.1038/s41598-018-30077-6.

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