Institute of
bioorganic chemistry

CRISPR-Cas systems are widely recognized as a genome editing tool. In nature, these systems play the role of bacterial adaptive immunity against bacteriophages and other mobile genetic elements. It is generally believed that mutations are responsible for overcoming such defenses. In a study led by Konstantin Severinov involving several groups from Russia, the United States and Chile, it was found that even with a fully functional CRISPR-Cas and an unmutated target sequence, the plasmid can persist for many generations in a small subpopulation of E. coli cells. A model system using fluorescent proteins made it possible to trace the activity of the CRISPR-Cas system at the level of single living bacterial cells. The work was published in the Proceedings of the National Academy of Sciences of USA.

Scientists from the Laboratory of proteolytic enzyme chemistry IBCh RAS in collaboration with colleagues from National Cancer Institute (Frederick, USA) published the review on structural studies of ATP-dependent Lon proteases – key components of the protein quality control system. Targets of Lon proteases are mutant, damaged and some regulatory proteins. Three subfamilies have been identified in the Lon family, whose representatives are formed by ATPase domains of the AAA+ protein superfamily, serine–lysine peptidases and differing inactive extra domains. Barrel-shaped hexamers of Lon proteases bind protein targets, unfold them and translocate to an internal degradation chamber, where they undergo proteolysis. 3D analysis was used to obtain data on the structure of both individual domains and multi-domain fragments of different subfamilies’ Lon proteases. The use of cryo-electron microscopy made it possible to solve the structures of a number of full-length Lon proteases, as well as to describe the state of the enzymes at different stages of the catalytic cycle. The review is published in the Journal of Molecular Biology.

Team of scientists from the Department of immunology and the Department of Peptide and Protein Technologies IBCh RAS in collaboration with colleagues from Nursery for laboratory animals, GPI RAS and MEPhI introduce the concept of genetically-encoded bioluminescence resonance energy transfer (BRET)-activated photodynamic therapy (PDT). Being targeted to tumor cells, genetically-encoded NanoLuc-miniSOG construct generates internal light source and sensitizer pair, which makes possible PDT effect under BRET activation to treat tumors at virtually unlimited depth. The results are published in the Light: Science & Applications. Learn more

Traditionally, cytogenetic and molecular cytogenetic methods are used to detect chromosomal abnormalities. With the development of sequencing technologies, new approaches have become available to identify structural variations ranging from 50 bp. Researchers from the Laboratory of Molecular Oncology of Institute of Bioorganic Chemistry of the Russian Academy of Sciences and the Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency developed an approach for construction of CNV validation set at the exon level and evaluated the efficiency of CNV calling tools designed for whole exome sequencing data. The work is published in the Scientific Reports and International Journal of Molecular Sciences. Learn more

Scientists from the group of molecular tools for living system studies and laboratory of molecular diagnostics (IBCH) together with the colleagues from Skoltech, the Federal Research Center for Physical and Chemical Medicine, Massachusetts Institute of Technology (USA) and Instituto de Química-Física Rocasolano (Spain) has developed a DNA modification, 7,8-dihydro-8-oxo-1,N6-ethenoadenine (oxo-ϵA), a non-natural synthetic base that combines structural features of two naturally occurring DNA lesions (7,8-dihydro-8-oxoadenine and 1,N6-ethenoadenine). The ability of oxo-ϵA to mimic the natural base thymine and regulate duplex stability, as well as its strong fluorescence and invisibility to enzymatic repair systems in vivo, are properties that may find application in the development of nucleic acid-based molecular tools and therapeutics. The work was published in Nucleic Acids Research.