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Ekaterina Savitskaya

Professor: Konstantin Severinov

Ekaterina was graduated from Biological department of Moscow State University, in 1998. She completed her postgraduate project at the Institute of Gene Biology, Russian Academy of Sciences, and defended the thesis entitled “Mechanism of action of Drosophila melanogaster Su(Hw) insulator” in 2001. Ekaterina joined Skoltech in 2013 to study CRISPR-Cas prokaryotic immunity, she’s mainly interested in details of the adaptive CRISPR spacer acquisition process, and in the interactions of CRISPR-Cas systems with cell genome maintaining machinery.

CRISPR is a prokaryotic system that provides acquired immunity against plasmids and phages. This system is comprised of a cluster of short repeats (24-47bp long), interspersed by similarly sized non-repetitive sequences (called spacers), and a set of CRISPR-associated (cas) genes. CRISPRs are found in ~40% of bacterial and ~99% of archaeal genomes sequenced to date. CRISPR loci are transcribed into a single RNA transcript, which is then further cleaved by the Cas proteins to generate smaller CRISPR RNA units, each including one targeting spacer. These units, in complex with Cas proteins, interfere with mobile genetic elements by base-pairing with matching foreign DNA and leading to its cleavage and degradation. In response to phage (or plasmid) infection bacteria can integrate new spacers identical to the phage genomic sequence (termed protospacer), resulting in the appearance of adaptive CRISPR-mediated phage resistance. While there have been great advances in the biochemistry of CRISPR action, the details of the process as well as its influence on bacteriophage-bacteria co-evolution remain to be elucidated.

  1. Highly efficient primed spacer acquisition from targets destroyed by the Escherichia coli type I-E CRISPR-Cas interfering complex. Semenova E, Savitskaya E, Musharova O, Strotskaya A, Vorontsova D, Datsenko KA, Logacheva MD, Severinov K. Proc Natl Acad Sci U S A. 2016 113(27):7626-31.
  2. Diversity of CRISPR-Cas-mediated mechanisms of adaptive immunity in prokaryotes and their application in biotechnology. Savitskaya EE, Musharova OS, Severinov KV. Biochemistry (Mosc). 2016 81(7):653-61.
  3. Foreign DNA acquisition by the I-F CRISPR-Cas system requires all components of the interference machinery. Vorontsova D, Datsenko KA, Medvedeva S, Bondy-Denomy J, Savitskaya EE, Pougach K, Logacheva M, Wiedenheft B, Davidson AR, Severinov K, Semenova E. Nucleic Acids Res. 2015 43(22):10848-60.
  4. The Cas6e ribonuclease is not required for interference and adaptation by the E. coli type I-E CRISPR-Cas system. Semenova E, Kuznedelov K, Datsenko KA, Boudry PM, Savitskaya E, Medvedeva S, Beloglazova N, Logacheva M, Yakunin AF, Severinov K. Nucleic Acids Res. 2015 Jul 13;43(12):6049-61.
  5. Rapid multiplex creation of Escherichia coli strains capable of interfering with phage infection through CRISPR. Strotksaya A, Semenova E, Savitskaya E, Severinov K. Methods Mol Biol. 2015;1311:147-59.
  6. The Digital Ageing Atlas: integrating the diversity of age-related changes into a unified resource. Craig T, Smelick C, Tacutu R, Wuttke D, Wood SH, Stanley H, Janssens G, Savitskaya E, Moskalev A, Arking R, de Magalhães JP. Nucleic Acids Res. 2015;43(Database issue):D873-8.
  7. Pervasive Generation of Oppositely-Oriented Spacers during CRISPR Adaptation. Shmakov S*, Savitskaya E*, Semenova E, Datsenko K, Severinov K. Nucleic Acids Res. 2014;42(9):5907-16.         *-equally contributed
  8. High-throughput analysis of type I-E CRISPR/Cas spacer acquisition in E. coli. Savitskaya E, Semenova E, Dedkov V, Metlitskaya A, Severinov K. RNA Biol. 2013 Apr 25;10(5).
  9. Interaction between a pair of gypsy insulators or between heterologous gypsy and Wari insulators modulates Flp site-specific recombination in Drosophila melanogaster. Krivega M, Savitskaya E, Krivega I, Karakozova M, Parshikov A, Golovnin A, Georgiev P. Chromosoma. 2010 Aug;119(4):425-34.
  10. Several copies of insulator from MDG4 can determine the interaction between positively and negatively acting regulatory elements and promoter of the miniwhite gene of Drosophila melanogaster. Kostiuchenko MV, Savitskaia EE, Krivega MN, Georgiev PG. Genetika. 2008 Dec;44(12):1693-7. Russian.
  11. Zeste can facilitate long-range enhancer-promoter communication and insulator bypass in Drosophila melanogaster. Kostyuchenko M, Savitskaya E, Koryagina E, Melnikova L, Karakozova M, Georgiev P Chromosoma. 2009 Oct;118(5):665-74.
  12. The non-methylated DNA-binding function of Kaiso is not required in early Xenopus laevis development. Ruzov A*, Savitskaya E*, Hackett JA, Reddington JP, Prokhortchouk A, Madej MJ, Chekanov N, Li M, Dunican DS, Prokhortchouk E, Pennings S, Meehan RR. Development. 2009 Mar;136(5):729-38. *-equally contributed
  13. Study of functional interaction between three copies of the insulator from the MDG4 transposable element in the model system of the miniwhite gene of the Drosophila melanogaster. Kostyuchenko MV, Savitskaya EE, Volkov IA, Golovnin AK, Georgiev PG. Dokl Biochem Biophys. 2008 Jul-Aug;421:239-43. Russian.
  14. Red flag on the white reporter: a versatile insulator abuts the white gene in Drosophila and is omnipresent in mini-white constructs. Chetverina D, Savitskaya E, Maksimenko O, Melnikova L, Zaytseva O, Parshikov A, Galkin AV, Georgiev P. Nucleic Acids Res. 2008 Feb;36(3):929-37.
  15. PRE-mediated bypass of two Su(Hw) insulators targets PcG proteins to a downstream promoter. Comet I, Savitskaya E, Schuettengruber B, Negre N, Lavrov S, Parshikov A, Juge F, Gracheva E, Georgiev P, Cavalli G. Dev Cell. 2006 Jul;11(1):117-24.
  16. Study of the regulatory region of gene white of Drosophila melanogaster. Kostyuchenko MV, Savitskaya EE, Karakozova MV, Georgiev PG. Dokl Biochem Biophys. 2005 Nov-Dec;405:383-7. Russian.
  17. Study of long-distance functional interactions between Su(Hw) insulators that can regulate enhancer-promoter communication in Drosophila melanogaster. Savitskaya E, Melnikova L, Kostuchenko M, Kravchenko E, Pomerantseva E, Boikova T, Chetverina D, Parshikov A, Zobacheva P, Gracheva E, A, Georgiev P. Mol Cell Biol. 2006 Feb;26(3):754-61.
  18. Transposition of Regulatory Elements by P-Element-Mediated Rearrangements in Drosophila melanogaster. Pomerantseva E, Biryukova I, Silicheva R, Savitskaya E, Golovnin A, Georgiev P. Genetics. 2006 Apr;172(4):2283-91. Epub 2005 Dec 30.
  19. Pairing between gypsy insulators facilitates the enhancer action in trans throughout the Drosophila genome. Kravchenko E, Savitskaya E, Kravchuk O, Parshikov A, Georgiev P, Savitsky M. Mol Cell Biol. 2005 Nov;25(21):9283-91.
  20. The promoter region of the yellow gene of Drosophila melanogaster contains excess regulatory elements. Kostyuchenko MV, Georgiev PG, Savitskaya EE. Dokl Biochem Biophys. 2004 Nov-Dec;399:374-5. Russian.
  21. The Mod(mdg4) component of the Su(Hw) insulator inserted in the P transposon can repress its mobility in Drosophila melanogaster. Karakozova M, Savitskaya E, Melnikova L, Parshikov A, Georgiev P. Genetics. 2004 Jul;167(3):1275-80.
  22. Cis-modifiers of the yellow gene repression induced by the Su(Hw) insulator in the absence of the Mod(mdg4) protein in Drosophila melanogaster. Karakozova MV, Savitskaya EE, Parshikov AF, Georgiev PG. Dokl Biochem Biophys. 2003 Mar-Apr;389:110-3. Russian.
  23. An endogenous Su(Hw) insulator separates the yellow gene from the Achaete-scute gene complex in Drosophila. Golovnin A, Birukova I, Romanova O, Silicheva M, Parshikov A, Savitskaya E, Pirrotta V, Georgiev P. Development. 2003 Jul;130(14):3249-58.
  24. Loss of insulator activity by paired Su(Hw) chromatin insulators. Muravyova E**, Golovnin A, Gracheva E, Parshikov A, Belenkaya T, Pirrotta V, Georgiev P. Science. 2001 Jan 19;291(5503):495-8.
  25. New properties of the Su(Hw) insulator. Murav’eva EE*, Golovnin AK, Parshikov AF, Georgiev PG. Dokl Biochem Biophys. 2001 May-Jun;378:181-5. Russian.
  26. Insulators and interaction between long-distance regulatory elements in higher eukaryotes. Georgiev PG, Murav’eva EE*, Golovnin AK, Gracheva EM, Belen’kaia TIu.
    Genetika. 2000 Dec;36(12):1588-97. Review. Russian.

**Muravyova is a maiden name.

  • CRISPR-Cas prokaryotic immunity
  • Genome mobility vs genome maintenance
  • High throughput approaches in molecular genetics

Metchnikov stipend from French Embassy. 2016.

RFBR 2016-2018 (IMG RAS) Cross-talk between CRISPR-Cas system and mechanisms ensuring genome stability in Escherichia coli.

RFBR 2013-2014. (IMG RAS) The mechanisms of CRISPR/Cas interference regulation in Escherichia coli.

Grant of President of Russian Federation for young post-graduated scientists. Role of tne methyl DNA binding protein Kaiso in regulatation of gene expression. 2008-2009.