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• Upregulation of cholinergic modulators Lypd6 and Lypd6b associated with autism drives anxiety and cognitive decline November 18

  A duplication of the chromosomal region 2q23.q23.2, carrying LYPD6 and LYPD6B genes, leads to intellectual disability and autistic features. Researchers from the Neurotransmitter and Neuroreceptor Bioengineering Laboratory, Shemyakin-Ovchnnikov Institute of Bioorganic Chemistry of RAS together with colleagues from Lomonosov State University and Institute for Biomedical Problems of RAS, used a mouse model to study the consequences of overexpression of the Lypd6 and Lypd6b proteins in the brain, which is typical for patients with autism and other neuropsychiatric disorders.

• Origin, Evolution and Diversity of φ29-like Phages October 11

  The application of the definition of taxonomic species to the description of evolutionary history of biological objects with chimeric genomes is a difficult task. The limited period of the existence of species and the lability of viral genomes can also make attempts to reconstruct the evolutionary history almost pointless. The processes of genetic exchange seem to be especially pronounced in temperate phages, but genetic rearrangements between evolutionarily close groups of phages can also affect φ29-like phages. However, we can try to plot the evolutionary traits of genes encoding separate essential proteins and their stable complexes.

• Two-dimensional high-throughput on-cell screening of immunoglobulins against broad antigen repertoires July 12

  Identifying high-affinity antibodies in human blood serum is a non-trivial task due to the extremely small number of circulating B-cells with the specified specificity. A team of scientists from the IBCh RAS proposed an effective approach that allows for the identification of high-affinity antibodies against pathogen proteins while simultaneously mapping epitopes, even in the absence of information about the structure of the pathogen's immunogens. To screen therapeutic antibodies in the blood of recovered donors, only the pathogen's transcriptome is needed to create a polypeptide library of antigens displayed on the surface of a bacteriophage. The work was published in the journal Communications Biology.

• Synthesis of Substituted 1,2,4-Triazole-3-Thione Nucleosides Using E. coli Purine Nucleoside Phosphorylase July 4

  Scientists from the departments of biotechnology and structural biology (IBCH RAS) and Institute of the Chemistry of Plant Substances (Uzbekistan), and D. I. Ivanovsky Institute of Virology synthesized a series of substituted 1,2,4-triazole-3-thione nucleoside analogs and tested their antiviral activity against herpes simplex virus.

• “Molecular portraits” characterized functional states of TRPV ion channels June 28

  TRPV ion channels realize a huge variety of functions in the human body participating in the temperature and pain sensation, cell division, calcium uptake. Researchers from IBCh RAS and Columbia University analyzed the structure of the key TRPV domain – the ion conducting pore. Using the original “dynamic molecular portrait” approach, they identified three major states of the pore that are common for all TRPVs, called α-closed, π-closed, and π-open. It was shown that the α-closed state is the most hydrophobic and always nonconducting. While the π-closed one is less stable and can easily transit to the open state, which has favorable hydrophobic properties for the ion conduction. The results were published in Communications Chemistry.

• Immune system regulation for nanoparticle drug delivery. Breaking the endless cycle in nanomedicine June 14

  The journey of discovery in scientific research sometimes follows a familiar path: discover, admire, investigate, disappoint, and forget. Nevertheless, in some disciplines, it seems repeating many times. One of such cycles in the field of immune system blockade by nanoparticles is analysed in a recent article published in Nature Communications journal. Scientists from the Institute of Bioorganic Chemistry, Uppsala University and Boston University propose that advancements in nanomaterial development may finally disrupt this cycle, potentially introducing the method of macrophage blockade into clinical practice to improve cancer therapy.

• Loss of Ability to regenerate Limbs in Higher Vertebrates: From Side Effects of Evolutionary Innovations to Gene Loss June 5

  Researchers from the Laboratory of Molecular Foundations of Embryogenesis at the GNC IBCh RAS have identified the main factors that rendered limb regeneration impossible in modern amniotes (reptiles, birds, and mammals). The authors suggested that after the ancestors of amniotes transitioned to land, their ability to regenerate limbs was suppressed by the side effects of various innovations that emerged at that time, which were necessary for successful colonization of land. This, in turn, stimulated the disappearance of many genes that ceased to participate in regeneration from that moment on. As a result, in modern amniotes, including humans, the inability to regenerate limbs became firmly fixed at the genomic level.

• Innovative Contact Lenses with Metal-Organic Frameworks for Glaucoma Treatment May 13

  Researchers from the Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Harvard University, Sechenov University, the Pasteur Institute, and other scientific institutions in Russia and abroad have proposed a new method for controlling elevated intraocular pressure, which is a major damaging factor in glaucoma. They have developed a new type of contact lenses that incorporate metal-organic frameworks (MOFs) for the controlled and prolonged release of brimonidine, a medication used to reduce intraocular pressure. This innovation was presented in the high-ranking scientific journal Aggregate, highlighting its innovative nature and potential impact on ophthalmological practice.

• NMR spectroscopy reveals patterns and thermodynamic parameters of dimerization of β- hairpin antimicrobial peptides in the membrane April 10

  The staff of the Laboratory of structural biology of ion channels and the Science–Educational center for the first time studied the thermodynamics of the dimerization process of a β-hairpin peptide in the membrane-mimicking environment of detergent micelles using the example of the antimicrobial peptide (AMP) capitellacin of the marine polychaete Capitella teleta. The study also describes the mechanism of capitellacin action on bacterial membranes. The results of the work were published in the journal Biomolecules.

• Human RPF1 and ESF1 in Pre-rRNA Processing and Assembly of Pre-Ribosomal Particles: A Functional Study March 6

  Ribosome biogenesis is a sophisticated time-ordered process, which adjusts the protein synthesis rate to consumption of nutrients and external stimuli. It begins with transcription of the ribosomal primary RNA precursor. 13.3 kB 47S (fig.) pre-rRNA processing is coupled with the sequential recruitment of ribosome biogenesis factors and non-coding RNAs as well as ordered coating of rRNA with ~80 ribosomal proteins during formation of the functional 60S and 40S ribosomal subunits.

• The rational design of an efficient biocatalyst for the phosphoribosylation of antiviral pyrazine-2- carboxamide derivatives February 27

  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 molecular mechanism of body axis induction in jawless vertebrates may differ from that described in gnathostomes February 26

  A significant proportion of modern ideas about the molecular mechanisms of body axis induction and differentiation of vertebrate embryos are based on studies of classical laboratory model objects - fishes, amphibians and mammals - that belong to only one of the two major clades of extant vertebrates - gnathostomes. In these animals, genes of Noggin family have been described as key embryonic inducers of the main body axis.

• The loss of the classical embryonic inducer noggin1 in cartilaginous fish may be associated with the formation of their unique skeleton February 19

  The discovery of the neural inducer Noggin1 in 1992 was one of the most important events in the history of molecular developmental biology. Subsequently, several genes of the Noggin family were discovered and described in vertebrates, which appeared as a result of genomic duplications in ancestral vertebrates and differed in their expression patterns and functional properties. A series of studies carried out at the Laboratory of Molecular Bases of Embryogenesis of the Institute of Bioorganic Chemistry, Russian Academy of Sciences, in 2006-2020, was devoted to the study of Noggins in vertebrates. The key roles of Noggins in the regulation of intracellular signaling cascades and a wide range of developmental processes, including the development of the telencephalon unique to vertebrates, have been demonstrated.

• CRISPR/Cas9-mediated мultiplexed multi-allelic mutagenesis of genes located on A, B and R subgenomes of hexaploid triticale February 12

  This research, performed by the members of the Laboratory of Expression Systems and Plant Genome Modification (BIOTRON), Department of Plant Molecular Biology and Biotechnology, together with colleagues from the All-Russia Research Institute of Agricultural Biotechnology, reports the first time production of edited hexaploid triticale (× Triticosecale) through CRISPR/Cas9-mediated multiplexed induction of multilocular mutations in genes associated with starch biosynthesis.

• Obtaining Gene-Modified HLA-E-Expressing Feeder Cells for Stimulation of Natural Killer Cells February 2

  In response to cytomegalovirus (HCMV) infection, a pool of specialized “adaptive” NK cells with immunological memory traits develops in humans. This process is based on the recognition of HCMV peptides presented in the context of the HLA-E molecule by the activating receptor NKG2C. Using retroviral transduction, members of the Laboratory of Cell Interactions of the Immunology Department, IBCH RAS, together with colleagues from the European Medical Center, obtained K562-21E feeder cells expressing HLA-E and identified a subpopulation, whose size is associated with the magnitude of NK cell proliferative response to the presentation of the HCMV peptide. The K562-21E cells can be applied both for the accumulation of HCMV-specific NK cells and for studying the adaptive cells maturation.  

• Multiple paralogs of foxg1, the regulator of forebrain development, in lampreys and sturgeons: the legacy of genomic duplications in the early evolution of vertebrates January 25

  The forebrain of vertebrates, including its unique rostral section, the telencephalon, provides the highest forms of nervous activity in animals and humans. The foxg1 gene has been described as one of the leading regulators of early forebrain development. It has been shown that disturbances in the expression of foxg1 lead to developmental abnormalities and a decrease in the size of the forebrain, called FOXG1 syndrome in humans.  

• Hydrogen peroxide is not generated intracellularly in human neural spheroids during ischemia-reperfusion January 23

  Reactive oxygen species (ROS) are considered a primary source of damage during an ischemic stroke. Studies on this subject are usually performed on either cell culture or animal models, which can make it difficult to translate the results to humans. Currently, 3D neurospheroids derived from induced pluripotent stem cells (iPSCs) are proposed as an optimal alternative for modeling disease conditions.

• Age-dependent astrocytic atrophy and mitochondrial malfunction in human neocortex December 25, 2023

  In this groundbreaking study researchers have delved into the intricate cellular changes occurring in the brains of aging adults. The study, conducted on neocortical tissue from individuals aged 22 to 72 years, provides unprecedented insights into the impact of aging on astrocytes and neurons.

• A non-canonical RNAi pathway induced by externally applied virus-specific dsRNA in plants December 7, 2023

  The external application of dsRNAh has recently been developed as a new approach for crop protection. It is assumed that the mechanism of dsRNA-mediated antivirus RNA defence is similar to that of natural RNA interference (RNAi). There is, however, no direct evidence to support this idea. Scientists from the IBCh RAS in collaboration with colleagues from JHI (UK) we carried out the analysis of small RNAs (sRNA) as hallmarks of RNAi induced by potato virus Y (PVY).

• Redox differences between neonatal and adult cardiomyocytes under hypoxia December 4, 2023

  It is a known fact that oxidative stress plays a key role in the pathogenesis of coronary heart disease. However, why do neonatal cardiomyocytes exhibit greater resistance to hypoxia compared to adult cell types?

• Venom-gland transcriptomics and venom proteomics of the Tibellus oblongus spider November 28, 2023

  The Scientific Data journal published the paper “Transcriptomics of Venom Glands and Proteomics of Venom of the Spider Tibellus Oblongus,” which describes a comprehensive study of the venom of the Central Asian spider. As a result of the analysis of the transcriptome of the venom glands and the venom proteome, more than 200 new peptide molecules were discovered, including both toxins with a classical organization and with unique structural motifs.