Institute of
bioorganic chemistry

The team from the Department of metabolism and redox biology together with Russian and foreign colleagues from Belgium and France, has developed a new analytical tool that allows registering (pseudo)hypohalous stress in living systems at subcellular resolution in real-time mode. The indicator was characterized in detail in vitro, and the spatial structure of a redox sensor based on a circularly permuted fluorescent protein was established for the first time. The resulting instrument was used to visualize the dynamics of active halogen species in the model of inflammation caused by the amputation of Danio rerio caudal fin. The work was published in Nature Communications journal. Learn more

Telomerase RNA is one of the core components of the telomerase complex and participates in survival mechanisms that are activated under stress conditions. Human telomerase RNA protein (hTERP) is encoded by telomerase RNA and has been recently shown to be involved in autophagy regulation. In this studya team of scientists from the Laboratory of Molecular Oncology of the IBCh RAS, MSU, and SRI PCM FMBA of Russia demonstrated the role of hTERP in the modulation of signaling pathways regulating autophagy, protein biosynthesis, and cell proliferation. The AMPK signaling pathway was affected in cells deficient of hTERP and when hTERP was overexpressed. The appearance of hTERP is important for metabolism switching associated with the accelerated proliferation of cells in healthy and pathological processes. These findings demonstrate the connection between telomerase RNA biogenesis and function and signaling pathways. The results are published in the Frontiers in Cell and Developmental Biology journal.

Embryos of many organisms are able to maintain the invariance of their structure, regardless of size – the so-called phenomenon of embryonic scaling. For example, embryos of sea urchin or frog, which have developed from individual cells isolated shortly after the beginning of egg cleavage, self-regulate their structure so that they appear as smaller copies of normal ones. Researchers at the Laboratory of Molecular Bases of Embryogenesis at the IBCH RAS have proposed a general approach to the study of the mechanisms of embryonic scaling. They heuristically postulated and then mathematically proved the existence of special genes, named scalers, the expression of which depends on the embryo size, developed a method for targeted search of such genes, and, as proof of principle, disclose the mechanism by means of which one of the found scalers, mmp3, regulates patterning of Xenopus laevis embryo in a size-dependent manner. This work was published in the Developmental Cell journal. Learn more

Researchers from the Institute of Bioorganic Chemistry, Russian Academy of Sciences, from the Laboratory of Receptor Cell Biology, Laboratory of Molecular Theranostics and the Group of Molecular Physiology, together with colleagues from the I Prokhorov General Physics Institute and Moscow State University, a genetically encoded fluorescent sensor for measuring the pH of the extracellular medium in the slightly alkaline range has been created. To accomplish this task, a number of chimeric proteins were obtained, which are the previously described pH sensor SypHer3s with different transmembrane domains: from CIRL2, ErBb2, TrkA, IR, and neurexin-1. Among these fusion proteins, only the variant with the transmembrane domain of neurexin-1 was localized on the cell membrane. This protein was named SypHerExtra. Using the method of fluorescence lifetime imaging microscopy (FLIM) on living tumor cells, it was demonstrated that SypHerExtra can be successfully used to determine extracellular pH, while SypHer3s can be used to measure intracellular pH. The results are published in the journal Biosensors. Learn more

Nanoparticles based on the biocompatible amphiphilic poly(N-vinylpyrrolidone) (Amph-PVP) derivatives are promising for drug delivery. Also, many efforts have been made to exploit the DR5-dependent apoptosis induction for cancer treatment. Researchers from the IBCh RAS together with colleagues from the MUCTR, MSU and FMBA of Russia fabricated Amph-PVP-based nanoparticles covalently conjugated with antitumor DR5-specific TRAIL (Tumor necrosis factor-related apoptosis inducing ligand) variant DR5-B and evaluated their in vitro cytotoxicity in 3D tumor spheroids. The nanoparticles were found to enhance cytotoxicity effects compared to those of free DR5-B in both 2D and 3D in vitro models. Taking into account the nanoparticles loading ability with a wide range of low-molecular weight antitumor chemotherapeutics into hydrophobic core and feasibility of conjugation with hydrophilic therapeutic molecules by click chemistry, it can further be developed to a versatile system for targeted drug delivery into tumor cells. The results are published in Pharmaceutics.