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Contract number
14.B25.31.0004
Time span of the project
2013-2017

As of 30.01.2020

25
Number of staff members
34
scientific publications
4
Objects of intellectual property
General information

Name of the project: Molecular, ecological and applied microbiology

Strategy for Scientific and Technological Development Priority Level: в


Goals and objectives

Research directions: - Search for new antibiotics and biologically active components based on peptides and modernization of existing ones, functional analysis of adaptive defense systems

- Search for new CRISPR-Cas systems for development of new genetic engineering technologies, analysis of impact of stochastic effects on work of restriction-modification systems that contribute to bacterial persistence

- Describing new transcription agents of bacteriophage ferments

Project objective: Creation of a modern laboratory of molecular, ecological and applied microbiology at the Peter the Great Saint Petersburg Polytechnic University


The practical value of the study

  • Our researchers were the first to characterize unique RNA polymerases of giant bacteriophages. For one of them we have produced a model of 3D structure which is as of today, the first model of a non-canonical transcription ferment.
  • Using acoustic force spectroscopy we have accumulated data at the single-molecule level on inhibition of bacterial RNA polymerase by new lasso peptides.
  • We have performed complete structural and biochemical characterization of a new antimicrobial thiazole oxazole modified microcin (ТОММ), klebsazolicin, that inhibits growth of bacteria by blocking transcription. Using biochemical, genetic and X-ray structural methods we have determined that klebsazolicin inhibits elongation of a growing peptide chain by blocking the ribosome tunnel.
  • Our researchers have developed unique algorithms for analysis of images obtained using fluorescent microscopy. This allowed to obtain high quality data on variation from cell to cell between components of defense systems of bacteria (restoration-modification systems and CRISPR-CAS systems) at to find out how this variability affect the fate of individual cells.

Education and career development:

  • Two PhD these at the Skolkovo Institute of Science and Technology, 6 candidate dissertation, 15 undergraduate theses have been defended.
  • The composition of the Laboratory's staff includes: 9 postgraduates, over 20 students of the Peter the Great Saint Petersburg Polytechnic University, 3 students of the Saint Petersburg State University, 10 students and postgraduates of the Skolkovo Institute of Science and Technology.
  • Internships have been organized at leading Russian and international research and education centers for 20 young researchers and postgraduates of the Laboratory.
  • We have organized the open lecture by the Nobel Prize winner professor Shinya Yamanaka «Latest advancements in research and applications of induced pluripotent stem cells».
  • Four seminars with invited foreign researchers have been organized.
  • New educational courses have been created «Single molecule methods in biological research» for postgraduates of the Laboratory, the educational case study course «Basics of molecular biology» for students of the Department of Biophysics of Peter the Great Saint Petersburg Polytechnic University.
  • We have provided case study courses in methods of molecular ecological and applied microbiology for 12 young researchers and postgraduates from other organizations.
  • We have organized tours at Laboratory for school students.
  • We have organized the «Satellite Young Scientists School on Genomics and Metagenomics of Extremophiles» scientific school in which leading biologists have participated – Konstantin Severinov, Mikhail Gelfand, Dennis Bamford, Michael Terns and Armen Mulkidjanian.

Organizational and structural changes:

  • The Laboratory has purchased expensive equipment (a AB Sciex 5800 MALDI TOF-TOF spectrometer, a complex of equipment for single-molecular research on the basis of spectrometer with a surface acoustic wave).
  • We have furnished two laboratory rooms for conducting molecular microbiological research which gives the Peter the Great Saint Petersburg Polytechnic University new opportunities to conduct biological research.

Other results: The number of collaborative projects of the university both with Russian and foreign universities has increased.

Collaborations:

  • Skolkovo Institute of Science and Technology (Russia): implementation of the collaborative project «Nucleases transported by adeno-associated viruses for new generation agents for genetic therapy of hereditary diseases» together with our industrial partner «BIOCAD» CJSC and with support of the Ministry of Science and Higher Education of the Russian Federation
  • Rutgers University (USA), Massachusetts Institute of Technology (USA), University of Texas (USA), Pasteur Institute (France): joint research, scientific internships of young scientists

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Yakunina M., Artamonova T., Borukhov S., Severinov K., Minakhin L.
A Non-Canonical Multisubunit RNA Polymerase Encoded by a Giant Bacteriophage. Nucleic Acids Research 43(21): 10411–10420 (2015).
Morozova N., Sabantsev A., Bogdanova E., Fedorova Y., Maikova A., Vedyaykin A., Rodic A., Djordjevic M., Khodorkovskii M., Severinov K.
Temporal Dynamics of Methyltransferase and Restriction Endonuclease Accumulation in Individual Cells after Introducing a Restriction-Modification System. Nucleic Acids Research 44(2): 790–800 (2016).
Metelev M., Tietz J.I., Melby Joel O., Blair P.M., Zhu L., Livnat I., Severinov K., Mitchell D.A.
Structure, Bioactivity, and Resistance Mechanism of Streptomonomicin, an Unusual Lasso Peptide from an Understudied Halophilic Actinomycete. Chemistry and Biology 22(2): 241–250 (2015).
Lavysh D., Sokolova M., Minakhin L., Yakunina M., Artamonova T., Kozyavkin S., Makarova K.S., Koonin E.V., Severinov K.
The Genome of AR9, a Giant Transducing Bacillus Phage Encoding Two Multisubunit RNA Polymerases. Virology 495: 185–196 (2016).
Metelev M., Osterman I.A., … Severinov K., Polikanov Y.S.
Klebsazolicin Inhibits 70S Ribosome by Obstructing the Peptide Exit Tunnel. Nature Chemical Biology 13(10): 1129–1136 (2017).
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