Severinov Laboratory

AboutTeamPublicationsFundingThesis defencesCourses

Start date – March 2013

Research in Severinov lab involves three main directions, CRISPR-Cas systems, bacteriophages, and antibiotics.

  • Bacterial viruses, bacteriophages, are most abundant and diverse live objects on our planet. They evolved a trove of mechanisms to destroy bacteria. Bacteriophages can also be used directly as antibacterial agents. We identify new bacteriophages from environment, determine their genomic sequences and identify molecular mechanisms that they use to effectively infect bacterial hosts. The knowledge gained produces targets for future development of antibacterial drugs.
  • Adaptive bacterial immunity CRISPR-Cas systems have revolutionized the field of genomic editing and opened up possibilities for genomic medicine. In collaboration with laboratories from NIH and MIT we predict and functionally characterize new CRISPR-Cas systems that may have advantages over existing ones in practical applications. We also study the biological role of various CRISPR-Cas systems, trying to understand how they shape the interactions of bacteria with mobile genetic elements such as bacteriophages and impact bacterial ecology and evolution. To this end, we a combination of advanced biochemical, genetic, biophysical and bioinformatics methods.
  • Antibiotic resistance becomes a global healthcare problem that may undermine the humankind ability to control bacterial diseases. We use bioinformatics to search for new antibiotics by mining available genomic and metagenomic data and we experimentally validate predicted antibiotic biosynthesis clusters and characterise new antibiotics they encode.  We determine the structures of validated compounds, mechanisms of their biosynthesis and action on sensitive cells. The knowledge gained is used to create semisynthetic bioactive compounds that can be developed for practical use in medicine and agriculture.
  • Ultrahigh-throughput functional profiling of microbiota communities.  Terekhov S, Smirnov I, Malakhova M, Samoilov A, Manolov A, Nazarov A, Danilov D, Dubiley S, Osterman I, Rubtsova M, Kostryukova E, Ziganshin R, Kornienko M, Vanyushkina A, Bukato O, Ilina E, Vlasov V, Severinov K, Gabibov A, Altman S. Proc Natl Acad Sci U S A, 2018 Sep 4.  doi: 10.1073/pnas.1811250115.
  • Diversity and evolution of class 2 CRISPR-Cas systems. Shmakov S, Smargon A, Scott D, Cox D, Pyzocha N, Yan W, Abudayyeh O, Gootenberg J, Makarova KS, Wolf Y, Severinov K, Zhang F, Koonin E. Nat Rev Microbiol. 2017 Mar;15(3):169-182. doi: 10.1038/nrmicro.2016.184. Epub 2017 Jan 23. PubMed PMID: 28111461.

 

Research grants/Industry funded research

Engineering thermophage particles for studying virus assembly
Obtaining and biochemical characterization of Cas9 protein with CJSC
Identification of Key genetic/epigenetic Marker(s) in cervical carcinogenesis and development of corresponding Molecular Therapeutics for precision medicine of cervical cancer
Relationship between interference and adaptation during the action of Type I-E CRISPR-Cas system of Escherichia coli
Computational approach for discovery of new CRISPR-Cas associated proteins
Study of the mechanisms of foreign DNA recognition by bacterial defense system BREX from Escherichi coli HS
Delivery of New Nucleases by AAV for Gene Therapy of Hereditary Diseases
Study of the regulation of expression of the genes of the restriction-modification Kpn2I system

Skoltech Biomedical Initiative

Personalized bacteriophage therapy of clostridium Difficile Infections

Next Generation Program: Skoltech – MIT Joint Projects

Search and Development of New Genome Editing Tools for Biomedicine and Biotechnology

Skoltech Translational and Research Innovation Program – STRIP

Development of Personal Genetic Screening System
A Platform Approach to Develop New Antibiotic Leads Based on Microcins

Systems biology fellowship

Comprehensive characterization of CRISPR-linked genes
PhD 2018
MSc 2018
PhD 2017
MSc 2017
MSc 2016
Advanced Molecular Biology Laboratory Practice
Molecular Biology Seminar