- Hypocrates is a genetically encoded fluorescent biosensor for (pseudo)hypohalous acids and their derivatives
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
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.
- FLIM-Based Intracellular and Extracellular pH Measurements Using Genetically Encoded pH Sensor
December 14, 2021
Determination of the pH value in living cells and tissues is of great importance in physiology and cell biology. Researchers from the Institute of Bioorganic Chemistry, Russian Academy of Sciences, from the Laboratory of Receptor Cell Biology, Laboratory of Molecular Theranostics and the Group of Molecular Physiology, together with colleagues from the I Prokhorov General Physics Institute and Moscow State University, a genetically encoded fluorescent sensor for measuring the pH of the extracellular medium in the slightly alkaline range has been created.
- In memory of Alexander Georgievich Petrenko
December 6, 2021
The FEBS Journal has published an obituary dedicated to our colleague, the head of the Laboratory of Receptor Cell Biology, the remarkable scientist Alexander Georgievich Petrenko, who died from COVID-19 in May 2021. The publication covers the scientific career of Alexander Petrenko, which lasted more than 4 decades. For more details on the publication, please follow the link: https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.16282
- IBCH RAS mourns passing of Richard Lerner
December 6, 2021
An outstanding scientist, director and president of the Scripps Research Institute (from 1987 to 2012), founding director of the Shanghai Institute for Advanced Immunochemical Studies, a member of the International Advisory Board of the IBCh RAS and a laureate of many international awards, Professor Richard Lerner passed away on December 2, 2021 at the age of 83. He made a huge contribution to the development of biological and medical sciences. The staff and administration of the IBCh RAS express their sincere condolences to the family, friends and colleagues of Richard Lerner.
- In vivo dynamics of acidosis and oxidative stress in the acute phase of an ischemic stroke
November 30, 2021
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.
- Barnase*Barstar-guided two-step targeting approach for drug delivery to tumor cells in vivo
November 19, 2021
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.
- Antigen-specific stimulation and expansion of CAR-T cells using membrane vesicles as target cell surrogates
November 11, 2021
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.
- Development of single-domain inhibitory antibodies targeting the ErbB3 receptor for cancer therapy
November 11, 2021
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.
- Engineered Removal of PD-1 From the Surface of CD19 CAR-T Cells Results in Increased Activation and Diminished Survival
November 8, 2021
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.
- DARPin_9-29-Targeted Gold Nanorods Selectively Suppress HER2-Positive Tumor Growth in Mice
November 8, 2021
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.
- First crystal structure of bacterial oligopeptidase B in an intermediate state: the roles of the hinge region modification and spermine
October 27, 2021
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.
- 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, 2021
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.
- Pseudomonas phage MD8: genetic mosaicism and challenges of taxonomic classification of lambdoid bacteriophages
October 8, 2021
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.
- The secreted protein disulfide isomerase Ag1, lost by ancestors of poorly regenerating vertebrates, is required for Xenopus laevis tail regeneration
October 6, 2021
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.
- Mechanism of coelenterazine chromophore photoinactivation from Beroe abissycola photoprotein is proposed
August 27, 2021
Scientists from IBCh RAS with colleagues from Photobiology Lab (IBP SB RAS) elucidated the structures of Beroe abissycola photoprotein’s chromophore photoinactivation products and proposed a mechanism of the photoinactivation process. The similarity of chemical transformations of photoprotein and GFP-like fluorescent protein chromophores was demonstrated for the first time. The results are published in Organic Letters. The project was funded by the RScF grant № 17-14-01169p.
- Essential role of zinc ions in TLR1 receptor activation
August 24, 2021
Toll-like receptors are the key players of the innate immune response. Despite the numerous studies and huge amount of data regarding these proteins, the structural basis of their functioning has not yet been clearly elucidated. Scientists from IBCh RAS, together with their colleagues from Moscow Institute of Physics and Technology and Changchun Institute of Applied Chemistry (China) discovered the essential role of zinc in the functioning of Toll-like receptor 1 and proposed possible mechanisms of zinc-mediated receptor activation. The work was funded by the RFBR grant 20-34-70024 and published in Communications Biology.
- New structural data allowed to study the mechanism of thermal activation of thermosensitive ion channels of the TRP family
August 12, 2021
Scientists from the Laboratory of biomolecular modeling of the IBCh RAS, together with colleagues from Columbia University (New York, USA), the University of Illinois (Peoria, USA), and the Institute of Physiology of the Czech Academy of Sciences (Prague, Czech Republic), have revealed the structural mechanism of heat-induced opening of temperature-sensitive TRP channels.
- Investigation of long-term fate of magnetic nanoparticles in mice
July 15, 2021
Scientists from Laboratory of molecular immunology of IBCh RAS performed first broad comprehensive study of factors which influence degradation rate of magnetic particles in mammals. For this aim magnetic spectral approach was developed, allowing non-invasive and quantitative measurement of magnetic particles in mice without influence of biogenic iron. Researchers studied the key factors that determine the degradation rate of nanoparticles: particle dose, size, zeta potential, type of polymer coating and internal architecture of nanoagents. The revealed deeper insights into the particle degradation in vivo may facilitate rational design of theranostic nanoparticles with predictable long-term fate in vivo. The work was published in ACS Nano.
- Complex-dependent histone acetyltransferase activity of KAT8 determines its role in transcription and cellular homeostasis
May 18, 2021
International research team together with researchers from IBCh RAS studied molecular mechanisms of histone acetyltransferase KAT8 activity. The enzyme regulates DNA compactization and gene transcription regulation by acetylation of histone H4 and is essential for cell viability. The results are published in the journal Molecular Cell.
- 2021 research grants
May 12, 2021
In 2021, we are offering a series of research grants to stimulate innovative research in challenging areas of future importance. Grants of 40,000 € - 450,000 € per year for up to 3 years are available in the areas as further specified below. More info - researchgrants.merckgroup.com.
- Conformational changes in the receptor tyrosine kinase IRR during activation were determined
April 5, 2021
Researchers of the Laboratory of Receptor Cell Biology IBCh RAS together with colleagues from the IPCE RAS and IC RAS carried out a study of the IRR structure by atomic force microscopy and small-angle X-ray scattering. The conformations of the receptor in the active and inactive states have been determined; on the basis of the obtained data, an activation mechanism has been proposed.
- The role of natural mutations of the human protein SLURP-1 in the pathogenesis of Mal de Meleda skin disease has been determined
March 29, 2021
Mal de Meleda (MDM) is recessively inherited palmoplantar keratoderma associated with mutations in a gene encoding SLURP-1 protein. SLURP-1 is a paracrine regulator of keratinocyte homeostasis interacting with the α7 type nicotinic acetylcholine receptor (α7-nAChR). This receptor participates in control of growth, terminal differentiation, apoptosis and cornification of keratinocytes. Dysregulation of the α7-nAChR function due to SLURP-1 deficiency or point mutations of this protein may underlie MDM pathogenesis.