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  • science news In vivo dynamics of acidosis and oxidative stress in the acute phase of an ischemic stroke November 30

    The team of the Department of metabolism and redox biology of Institute of Bioorganic Chemistry in collaboration with colleagues from the Federal Center of Brain Research and Neurotechnologies of the Federal Medical Biological Agency, Lomonosov Moscow State University and several other institutes have developed a technology that allows real time recording of intracellular metabolic processes in vivo. On the model of ischemic stroke in rodents, the new data were obtained on changes occurring in neurons during the development of pathology.

  • science news Barnase*Barstar-guided two-step targeting approach for drug delivery to tumor cells in vivo November 19

    To reduce side effects in the process of oncotherapy, it seems promising to use two-step targeting delivery of active agents, or pre-targeting: at the first stage, a non-toxic targeting module (also including antibody or non-immunoglobulin scaffolds) is selectively delivered to a cell of a certain molecular profile, and at the second stage, a cytotoxic agent capable of specifically interacting with the first module is administrated into the organism.

  • science news Antigen-specific stimulation and expansion of CAR-T cells using membrane vesicles as target cell surrogates November 11

    Development of CAR-T therapy led to immediate success in the treatment of B cell leukemia. Manufacturing of therapy-competent functional CAR-T cells needs robust protocols for ex vivo/in vitro expansion of modified T-cells. In this work, a team of scientists from the IBCh RAS in collaboration with a group of scientists from Dmitry Rogachev National Medical Research Center and colleagues from the Faculty of Biology of Moscow State University have created a new technology for the expansion of CAR T cells using artificial vesicles carrying surface tumor antigens. This approach will allow in the future to obtain CAR T-cells with improved functional properties and to minimize the level of premature "exhaustion" of the CAR T-cell population.

  • science news Development of single-domain inhibitory antibodies targeting the ErbB3 receptor for cancer therapy November 11

    The human ErbB3 receptor is an important pharmacological target in the treatment of various types of cancer. A variety of anti-ErbB3 monoclonal antibodies are currently in development and are classic immunoglobulins. However, the search for new sources of antibodies or nanoantibodies consisting only of the heavy chain is being conducted more and more actively. Thus, in this work, a team of scientists from the Laboratory of Biocatalysis of the IBCh RAS, together with colleagues from the Laboratory of Renewable Energy Sources of the Academic University discovered a group of new single-domain llama antibodies targeting the extracellular domain of ErbB3 using the phage display method. It was found that the single-domain antibodies are not only highly affine for various receptor epitopes, but also have an inhibitory effect on the growth of tumor cells expressing ErbB3.

  • science news Engineered Removal of PD-1 From the Surface of CD19 CAR-T Cells Results in Increased Activation and Diminished Survival November 8

    CAR-T cell therapy is the most advanced way to treat therapy resistant hematologic cancers, in particular B cell lymphomas and leukemias. T cells equipped ex vivo with chimeric receptor recognize target tumor cells and kill them. CAR-T cells that recognize CD19 marker of B cells (CD19 CAR-T) are considered the gold standard of CAR-T therapy and are approved by FDA. But in some cases, CD19 CAR-T cell therapy fails due to immune suppressive microenvironment.

  • science news DARPin_9-29-Targeted Gold Nanorods Selectively Suppress HER2-Positive Tumor Growth in Mice November 8

    Breast cancer is one of the most common cancer among women. According to the WHO, in 2020, over 2.2 million cases of this disease were registered worldwide. High level of HER2, a tyrosine kinase receptor, is associated with a more aggressive clinical behavior and poor prognosis for breast cancer patients.

  • science news First crystal structure of bacterial oligopeptidase B in an intermediate state: the roles of the hinge region modification and spermine October 27

    Oligopeptidase B (OpB) is a two-domain serine peptidase with trypsin-like substrate specificity. OpB belongs to the prolyl oligopeptidase (POP) family and are found only in bacteria and protozoa. It is known that OpB are pathogenesis factors of protozoan infections and protect bacterial cells from a number of antimicrobial peptides. Nevertheless, they are the least studied representatives of POP, especially bacterial OpB, for which there was a complete lack of structural information. The researches from IBC RAS together with those of NRC Kurchatov Institute and the IBOC of the National Academy of Sciences of Belarus managed to obtain crystal structures of bacterial OpB from Serratia proteomaculans (PSP) with a modified hinge region.

  • science news Mambalgin-2 inhibits growth, migration, and invasion of metastatic melanoma cells by targeting the channels containing an asic1a subunit whose up-regulation correlates with poor survival prognosis October 16

    Melanoma is aggressive cancer characterized by acidification of extracellular environment. Scientists from the Laboratory of bioengineering of neuromodulators and neuroreceptors IBCh RAS together with colleages from NN Blokhin NMRCO showed for the first time that extracellular media acidification increases proliferation, migration, and invasion of patient-derived metastatic melanoma cells and up-regulates cell-surface expression of acid sensitive channels containing the ASIC1a, α-ENaC, and γ-ENaC subunits. No influence of media acidification on these processes was found in normal keratinocytes.

  • science news Pseudomonas phage MD8: genetic mosaicism and challenges of taxonomic classification of lambdoid bacteriophages October 8

    Fundamental questions of the evolution of viral genomes are the most important topic of virological research. As a result of the joint work of virologists from the Laboratory of Molecular Bioengineering of the IBCh RAS and the Limnological Institute of the RAS, a group of bacteriophages of the dangerous pathogen Pseudomonas was identified, the genomes of these bacterial viruses were studied, and it was shown that their formation was greatly influenced by multiple horizontal transfers, which led to pronounced genetic mosaicism. Scientists also put forward hypotheses about the origin of the new group and proposed basic principles for the taxonomic classification of lambdoid phages.

  • science news The secreted protein disulfide isomerase Ag1, lost by ancestors of poorly regenerating vertebrates, is required for Xenopus laevis tail regeneration October 6

    As is known, unlike cold-blooded vertebrates, warm-blooded vertebrates are not able to regenerate such complex structures as a limb or tail. Earlier, researchers from the Laboratory of Molecular Bases of Embryogenesis IBCH RAS proposed a hypothesis about the relationship between the weakening of regenerative abilities in warm-blooded animals and the loss of some genes that regulate regeneration in cold-blooded animals. In support of this hypothesis, we showed that there are indeed genes essential for the regeneration among the found genes lost by warm-blooded vertebrates, particularly the gene for the secreted disulfide isomerase Ag1. Strong activation of this gene on 1 and 2 days post-amputation of the tail in a model object, the frog Xenopus laevis tadpoles, indicated its essential role at the beginning of regeneration processes. It was shown that knockdown of ag1 reduces the ability to regenerate the amputated tail. At the same time, this ability can be restored either by overexpression of ag1 or by the addition of its recombinant protein to the tadpoles.