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• Study of aging of contrast nanoparticles for MRI December 22, 2022

  A group of scientists from the Laboratory of Molecular Immunology of the IBCh RAS, GPI RAS and a several other scientific Institutes investigated biotransformation of magnetic nanoparticles in the body and the effect of this process both on the metabolism of the iron and on reducing the contrast properties of nanoparticles during imaging. For a long time, it remained unclear what happens in the long term with nanoparticle contrasts for MRI after their distribution in tissues. In addition, magnetic particle biodegradation is accompanied by abundant release of iron ions, which can cause toxic effects. A recent study published in the high-ranking Journal of Nanobiotechnology clarified these issues.

• New Type of Interaction of Snake Three-Finger α-Neurotoxins with Nicotinic Acetylcholine Receptors December 14, 2022

  Nicotinic acetylcholine receptor of α7 type (α7-nAChR) presented in the nervous and immune systems and epithelium is a promising therapeutic target for cognitive disfunctions and cancer treatment. Weak toxin from venom of cobra Naja kaouthia (WTX) is a non-conventional three-finger α-neurotoxin from Naja kaouthia venom, targeting α7-nAChR with weak affinity. There were no data on interaction mode of non-conventional neurotoxins with α7-nAChR.

• Identification of HLA-B*27-bound peptides recognized by TCRs associated with ankylosing spondylitis December 13, 2022

  Ankylosing spondylitis is an autoimmune rheumatological disease, where aberrant immune response against self-antigens is considered as a main trigger of the pathology. Up to date identification of antigen epitopes recognized by specific T cell receptors (TCRs), especially self-epitopes, remains tricky challenge and there is the very limited list of TCRs with characterized antigen specificity.

• Relationship between phenolic compounds and antioxidant activity in berries and leaves of raspberry genotypes and their genotyping using SSR markers November 21, 2022

  In recent years, the enrichment of fruits and berries with biologically active substances, in particular, antioxidants has received increased development in breeding (the creation of functional food). Researchers from the Forest Biotechnology Group of the FIBCh, together with colleagues from other institutes, studied the content of total phenols, flavonoids and anthocyanins, their relationship with the antioxidant activity of berries and leaves of various raspberry cultivars of Russian and foreign origin, as well as new breeding lines.

• A Single Fluorescent Protein-Based Indicator with a Time-Resolved Fluorescence Readout for Precise pH Measurements in the Alkaline Range November 17, 2022

  The real-time monitoring of the intracellular pH in live cells with high precision represents an important methodological challenge. Although genetically encoded fluorescent indicators can be considered as a probe of choice for such measurements, they are hindered mostly by the inability to determine an absolute pH value and/or a narrow dynamic range of the signal, making them inefficient for recording the small pH changes that typically occur within cellular organelles.

• Longitudinal profiling of human peripheral blood B cell clonal repertoire: memory B cell persistence and signs of negative and positive selection at the BCR repertoire level October 12, 2022

  Persistence of B cell clones and fine-tuning of their BCRs allow them to respond effectively to repeated immune challenges. Researchers from the Genomics of adaptive immunity department of IBCH in collaboration with colleagues from IITP and Skoltech, performed long-term study of structure and dynamics of BCR repertoire of memory B cells and antibody-secreting cells from peripheral blood of healthy donors.

• A Uniquely Stable Trimeric Model of SARS-CoV-2 Spike Transmembrane Domain August 31, 2022

  Tools created at the Laboratory of Biomolecular Modelling IBCh RAS have been brought together into a computational framework to build a model of SARS-CoV-2 spike transmembrane domain (TMD).

• Impact of Exogenous Application of Potato Virus Y-Specific dsRNA on RNA Interference, Pattern-Triggered Immunity and Poly(ADP-ribose) Metabolism in Potato Plants August 15, 2022

  Methods for inhibition of viral infection induced by spraying plants with preparations of specific double-stranded RNAs (dsRNAs) are currently being actively developed. Researchers from the Laboratory of functional genomics and plant proteomics, the Laboratory of Molecular Diagnostics and the Laboratory of Molecular Bases of Plant Stress Resistance of the Institute of Bioorganic Chemistry RAS studied the contribution of potato plant treatment with dsRNA against potato virus Y (dsRNA-PVY) to two dsRNA-induced plant defense mechanisms: specific RNA interference (RNAi) and non-specific pattern-triggered immunity (PTI).

• SOX9 Protein in Pancreatic Cancer Regulates Multiple Cellular Networks in a Cell-Specific Manner August 12, 2022

  Pancreatic ductal adenocarcinoma is one of the most lethal cancers worldwide. Sex-determining region Y-box protein 9 (SOX9) is upregulated in the majority of pancreatic ductal adenocarcinoma cases. It is hypothesized that the increased expression of pancreatic developmental factor SOX9 is necessary for the formation and maintenance of tumor phenotypes in pancreatic cancer cells.

• Therapeutic efficacy of antibody-drug conjugates targeting GD2-positive tumors July 19, 2022

  Both ganglioside GD2-specific immunotherapy and antibody-drug conjugates (ADCs), as a class of targeted drugs, have demonstrated clinical success as solid tumor therapies in recent years, yet practically no research has been carried out on ADCs directed to ganglioside GD2. In a new study, scientists from the Department of immunology at IBCh RAS in collaboration with colleagues from other Russian institutes for the first time show that clinically relevant anti-GD2 antibody-drug conjugates manifest potent and highly selective cytotoxicity in a wide panel of cell lines with varying GD2 expression and strongly inhibit tumor growth in mouse models of GD2-positive solid cancer.

• Synthesis of New 5ʹ-Norcarbocyclic Aza/Deaza Purine Fleximers - Noncompetitive Inhibitors of E.coli Purine Nucleoside Phosphorylase July 11, 2022

  Scientists from the Laboratory of biosynthesis of physiologically active compounds and Laboratory of biopharmaceutical technologies (IBCH RAS) and Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences synthesized a new series of flexible 5′-norcarbocyclic aza/deaza-purine nucleoside analogs and evaluated as potential inhibitors of E. coli purine nucleoside phosphorylase.

• Positively charged black hole quencher (BHQ) derivatives as external SERS active responsive elements of biosensors July 8, 2022

  Scientists from the Group of molecular tools for living system studies (IBCh RAS), Department of chemistry of Natural Compounds (Faculty of Chemistry, MSU) and Osipyan Institute of Solid State Physics, together with the Laboratory of Molecular Design and Synthesis (IBCh RAS), have developed external SERS-active responsive elements based on positively charged black hole quencher (BHQ) derivatives.

• Lignans as Pharmacological Agents in Disorders Related to Oxidative Stress and Inflammation: Chemical Synthesis Approaches and Biological Activities July 5, 2022

  Plant lignans are active components of many herbs, which makes them the research objects for therapeutic agents development for practical use. They provide diverse naturally-occurring pharmacophores, which allows them to interact with various enzymes, receptors, ion channels and signaling molecules.

• Streptocinnamides A and B, Depsipeptides from Streptomyces sp. KMM 9044 July 1, 2022

  A new structural group of antibiotics produced by a new strain Streptomyces sp. KMM 9044 was discovered as a result of teamwork of scientists from the Institute of Bioorganic Chemistry (IBCh RAS) and the Elyakov Pacific Institute of Bioorganic Chemistry (TIBOCh RAS).

• Capsule-Targeting Depolymerases Derived from Acinetobacter baumannii Prophage Regions June 16, 2022

  A team of scientists from the Laboratory of molecular bioengineering IBCh RAS together with the colleagues from other Russian Institutes bioinformatically predicted and recombinantly produced several different depolymerases encoded in the prophage regions of Acinetobacter baumannii genomes. For two depolymerases, the specificity to capsular polysaccharides (CPSs) of A. baumannii belonging to K1 and K92 capsular types (K types) was determined. These enzymes can be considered as suitable candidates for the development of new antibacterials against corresponding A. baumannii K types. 

• Evolution of Phage Tail Sheath Protein June 16, 2022

  A team of scientists from the Laboratory of molecular bioengineering IBCh RAS analysed 112 contractile phage tail sheath proteins (TShP) representing different groups of bacteriophages and archaeal viruses with myoviral morphology have been modelled with the novel machine learning software, AlphaFold 2. The common core domain of all studied sheath proteins, including viral and T6SS proteins, comprised both N-terminal and C-terminal parts, whereas the other parts consisted of one or several moderately conserved domains, presumably added during phage evolution.

• Heterogeneity of the GFP fitness landscape and data-driven protein design June 16, 2022

  Understanding the relationship between genotype and phenotype, the fitness landscape, elucidates the fundamental laws of heredity (Canale et al. 2018) and may ultimately create novel methods of protein design (Alley et al. 2019). The fitness landscape is often conceptualised as a multidimensional surface (Kondrashov and Kondrashov, 2015) with one dimension representing fitness, or another phenotype, and the other dimensions each representing a genotype’s locus.

• Synthesis of 2-chloropurine ribosides with chiral amino acid amides at C6 and their evaluation as A1 adenosine receptor agonists June 14, 2022

  The team of scientists from the Department of biotechnology and the Laboratory of structural biology of ion channels IBCh RAS synthesized a series of adenosine analogs as purine ribonucleosides bearing amino acid amides at the C6 position of 2-chloropurine.

• Сytoskeleton protein Zyxin inhibits retinoic acid signaling by destabilizing maternal mRNA of nuclear receptor RXRγ May 20, 2022

  In a new study, researchers from the Laboratory of molecular bases of embryogenesis, Institute of Bioorganic Chemistry, Russian Academy of Sciences, demonstrated the versatility of the previously discovered mechanism of maternal genes mRNA destabilization caused by an interaction between the cytoskeletal protein Zyxin and the mRNA-binding factor Ybx1, showing that the same mechanism governs the retinoic acid signaling pathway during early embryonic development.

• Genetically-encoded BRET-activated photodynamic therapy for the treatment of deep-seated tumors March 16, 2022

  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.

• Estimation of copy number variability from the high-throughput sequencing data March 14, 2022

  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.

• 7,8-Dihydro-8-oxo-1,N6-ethenoadenine: an exclusively Hoogsteen-paired thymine mimic in DNA that induces A→T transversions in Escherichia coli March 3, 2022

  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).

• Phospholipases A2 from snake venoms inhibit HIV replication February 9, 2022

  Since the beginning of HIV epidemic, lasting more than 30 years, the main goal of scientists was to develop effective methods for the prevention and treatment of HIV infection, including the search for new compounds with high activity against HIV. Studies carried out by the staff of the Department of Molecular Neuroimmune Signaling of the Institute of Bioorganic Chemistry of the Russian Academy of Sciences and the Gamaleya National Research Center for Epidemiology and Microbiology showed that phospholipases A2 (PLA2) from snake venom have a pronounced anti-HIV effect.

• Gene therapy 2.0: AAV beyond monogenic gene correction February 2, 2022
• Hypocrates is a genetically encoded fluorescent biosensor for (pseudo)hypohalous acids and their derivatives January 12, 2022

  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 (IF 14.919).

• Scalers: genes that regulate scale invariance of embryonic development January 10, 2022

  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.