Press-room / Digest

Nanoparticle surface mapping for rational design of drug delivery systems
To achieve control over the formation of a biomolecular corona, it is necessary to control the surface properties of nanoparticles (NPs). Hence, approaches to study the structure and dynamics of NPs surface with high resolution are required. Researchers from IBCh RAS and IC RAS proposed to generate topography maps of NPs surface from MD simulation data, and applied them to analyze the surface structure and dynamics of ligand-containing core–shell NPs. It has been shown that topography maps of NPs surface allow one to evaluate properties important for drug delivery systems. The work was published in the Biomaterials Science journal. Preprint available at ChemRxiv.

Human RPF1 and ESF1 in Pre-rRNA Processing and Assembly of Pre-Ribosomal Particles: A Functional Study
The scientists from the Department of functioning of living systems IBCh RAS demonstrated the involvement of early (nucleolar) ribosome biogenesis factors RPF1 and ESF1 in the maturation of ribosomal subunits. shRNA-mediated knockdown of these proteins demonstrated a unique change in the pre-rRNAs profile. These proteins in human cells, unlike yeast cells, are not vital, which allows us to argue about the probable rearrangement of the process to maintain the translational activity of cells. Based on the results obtained, authors suggest that the RPF1 and ESF1 proteins perform a structural function and contribute to the correct folding of RNA-protein complexes for further stages of pre-rRNA processing. The results are published in Cells. Learn more

New Phages Brutus and Scipio: Biology, Evolution, and Phage-Host Interaction
Researchers from the Laboratory of molecular bioengineering IBCh RAS, in collaboration with colleagues from other Russian institutions, have isolated and characterized two new virulent phages of the Obolenskvirus genus, which infect Acinetobacter baumannii, a significant nosocomial pathogen. The phages, named Brutus and Scipio, were capable of infecting A. baumannii strains corresponding to capsular types K116 and K82, respectively. The authors described the biological properties and genomic organization of the phages, and conducted comparative genomic, phylogenetic, and pangenomic analyses. Furthermore, they investigated the enzymatic activity of the tailspike depolymerase encoded in the genome of phage Scipio, marking the first registered virus to infect A. baumannii of the K82 capsular type. The exploration of new representatives within the Obolenskvirus genus enhances our understanding of the diversity of viruses in this taxonomic group and the interaction strategies between Obolenskvirus phages and their host bacteria. This work has been published in the International Journal of Molecular Sciences.

The rational design of an efficient biocatalyst for the phosphoribosylation of antiviral pyrazine-2- carboxamide derivatives
The antiviral T-1105 and T-705 (Favipiravir) compounds are inactive prodrugs that undergo metabolic transformation into the active form through phosphoribosylation in vivo. The efficiency of this process in human cells is very low, making the production of the phosphoribosylated pyrazine-2-carboxamide derivatives in vitro is a worthy challenge. The researchers from Dep. of Biotechnology of IBCh RAS, along with colleagues from MSU and FSRC “Crystallography and Photonics” RAS report the rational design of an efficient biocatalyst based on the hypoxanthine-guanine phosphoribosyltransferase from T. thermophilus (TthHGPRT). The rational design of TthHGPRT active site has allowed to engineer the D106G/Y155W mutant with a 325-fold increase in the rate of synthesis of T-705-riboside-5’-phosphate and 125-fold – T-1105-riboside-5’-phosphate. The reported results can become the basis for the new technologies of enzymatic production of antiviral compounds. The results are published in ACS Catalysis. Learn more

The molecular mechanism of body axis induction in jawless vertebrates may differ from that described in gnathostomes
In order to assess the conservatism of the induction mechanism in different evolutionary lines of vertebrates, the Laboratory of Molecular Basis of Embryogenesis carried out studies on the functional activity of Noggin genes in the lamprey as a representative of another, evolutionarily oldest group of vertebrates – cyclostomes (jawless). It turned out that despite the conservatism of the functional properties of the studied genes in experiments with amphibians, in whose embryos the lamprey Noggins are able to induce complete secondary body axes, a similar effect was not observed in the lamprey embryos themselves. These results may indicate differences in the mechanisms of major axis induction between gnathostomes and agnathans, opening new perspectives for research into the fundamental basis of this process. The results are published in International Journal of Molecular Sciences. Learn more