Press-room / Digest
Non-functional clonotypes are natural spike-in controls in T and B-cell receptor repertoires
The scientists from the Department of Adaptive Immunity Genomics of the IBCH RAS together with colleagues from the Rogachev NMRC DGOI developed the first fully computational method to correct quantitative bias in the T and B-cell receptor gene repertoires (TCR and BCR) obtained using multiplex PCR. These quantitative biases are associated with heterogeneous primer efficiencies and the exponential nature of PCR. This study identified multiplex PCR-specific anomalies in the frequencies of segments within the nonfunctional TCR and BCR rearrangements. OAR coefficients were proposed to quantify such anomalies, based on which an algorithm for quantitative bias correction was created. The efficiency of the algorithm was confirmed by several independent experiments. The results are published in the eLife.
Antibody fragment-drug conjugates selectively eliminate GD2-expressing tumor cells
Employing antibody fragments instead of full-length antibodies in antibody-drug conjugates can facilitate accumulation of the therapeutics in the tumor and reduce their side effects. Scientists from the Laboratory of molecular immunology together with colleagues from the Laboratory of cell interactions, the Laboratory of molecular diagnostics at IBCh RAS, and other Russian Institutes have for the first time developed GD2-specific antibody fragment-drug conjugates. Minibody and scFv fragment conjugates with the tubulin-inhibiting drugs MMAE and MMAF manifested strong cytotoxic and cytostatic effects in GD2-positive neuroblastoma and melanoma cell lines. The work is published in the International Journal of Molecular Sciences. Learn more
5-(Perylen-3-ylethynyl)uracil as an antiviral scaffold: Potent suppression of enveloped virus reproduction by 3-methyl derivatives in vitro
A group of scientists from the Laboratory of Molecular Design and Synthesis, the Protein Growth and Differentiation Factor Expression Group of the Institute of Bioorganic Chemistry, Russian Academy of Sciences, the Institute of Poliomyelitis and other institutes synthesized a series of compounds based on 5-(perylene-3-ylethynyl)uracil and studied their antiviral properties and mechanism of action. Previous studies of this class of compounds have suggested controversial types of mechanisms of action. Nonetheless providing comparable high activity. The present study showed that, upon irradiation with light, amphiphilic compounds accumulated in cell and viral membranes inhibit the entry of enveloped viruses into the cell. The results are published in the Antiviral Research. Learn more
Prophage-derived regions in Curtobacterium genomes: good things, small packages
Curtobacterium is a genus of Gram-positive bacteria within the order Actinomycetales. Some Curtobacterium species are harmful pathogens of agricultural crops such as soybean, dry beans, peas, sugar beet and beetroot, which occur throughout the world. About 200 publicly available genomes of Curtobacterium species, including environmental metagenomic sequences, were inspected for the presence of sequences of possible prophage origin using bioinformatic methods. One of the predicted temperate phages was induced from the Curtobacterium genome. Bioinformatic analysis of the modelled proteins encoded in prophage-derived regions led to the discovery of some 100 putative glycopolymer-degrading enzymes. These proteins can be considered for the experimental design of new antibacterials against Curtobacterium phytopathogens. The results are published in the International Journal of Molecualr Sciences. Learn more
Use of an Integrated Approach Involving AlphaFold Predictions for the Evolutionary Taxonomy of Duplodnaviria Viruses
One of the challenging tasks of Duplodnaviria taxonomy is the classification of high-ranked taxa, including families and orders. In this study, the team of scientists from the Laboratory of molecular bioengineering IBCh RAS in collaboration with the colleagues from the Limnological Institute analized the evolutionary relationships of conserved viral proteins, representing different viruses, including all classified Duplodnaviria families, using AlphaFold modelling. This analysis has been undertaken using structural comparisons and different phylogenetic methods. The results of the analyses mainly indicated the high quality of AlphaFold modelling and the possibility of using the AlphaFold predictions, together with other methods, for the reconstruction of the evolutionary relationships between distant viral groups. The results are publushed in the Biomolecules journal. Learn more