Institute of
bioorganic chemistry

A group of scientists from Laboratory of Comparative and Functional Genomics in collaboration with colleagues from Masaryk universities and Dmitry Rogachaev center for pediatric hematology, oncology and immunology developed a method for clonality assessment of human T-cell receptor alpha chain gene rearrangements. They showed for the first time that such rearrangements are found in approximately 50% of the tumors of patients with various oncohematological malignancies. The new method will improve minimum residual disease monitoring for the treatment of leukemia. Results of the study are published in British Journal of Haematology. Learn more

A sample-type protein monolayer, that can be a stepping stone to practical devices, can behave as an electrically driven switch. This feat is achieved using a redox protein, cytochrome C (CytC), with its heme shielded from direct contact with the solid-state electrodes. Ab initio DFT calculations, carried out on the CytC–Au structure, show that the coupling of the heme, the origin of the protein frontier orbitals, to the electrodes is sufficiently weak to prevent Fermi level pinning. Thus, external bias can bring these orbitals in and out of resonance with the electrode. Using a cytochrome C mutant for direct S–Au bonding, approximately 80% of the Au–CytC–Au junctions show at greater than 0.5 V bias a clear conductance peak, consistent with resonant tunneling. The on–off change persists up to room temperature, demonstrating reversible, bias-controlled switching of a protein ensemble, which, with its built-in redundancy, provides a realistic path to protein-based bioelectronics. Results of the study are published in Angewandte Chemie International Ediion.

A group of scientists from the Laboratory of the molecular immunology, in collaboration with colleagues from the universities of Tel Aviv and Modena, has shown the possibility of using gold nanorods (50 nm in length and 8 nm in diameter) for photothermal eradication of cancer cells by the near-infrared light. Coating of the nanorods (GNRs) with a HER2-specific DARPin, a module of non-immunoglobulin nature, yields stable DARPin-GNR conjugates capable of selective interaction with the surface of HER2-positive cells. Illumination by the near-infrared light (850 nm) led to almost complete eradication of cancer cells. Molecular dynamic simulations showed that a monolayer of DARPin molecules is formed on the surface of the nanorod. Conjugation with the nanorod does not involve the protein's domain responsible for specific binding to HER2. Our results provide the possibility of phototherapy tumors and metastases of deep tissues. The research was supported by the RSF grant No. 19-14-00112 and the results of the work were published in the journal ACS Applied Materials Interfaces.

Scientists from the University of Copenhagen, University of Southern Denmark, Memorial Sloan Kettering Cancer Center in New York, USA, Belarusian State University together with the scientist from Laboratory of Bioinformatic methods in Chemistry and Biology, IBCH RAS Kovalchuk S.I. studied the role of PRMT5 protein in cell functioning and its mode of action in leukemia in the model of human acute myeloid leukemia (AML) cells. PRMT5 activity was connected to SRSF1 protein direct regulation through Arg methylation. SRSF1 is an alternative splicing regulator and PRMT5 inhibition changes splicing patterns for a range of essential genes, which leads to AML cell death. The results of the work can provide potential biomarkers for the treatment response to PRMT5 inhibitors. The work was published in Nature Structural and Molecular Biology. Learn more

A group of scientists from the Laboratory of Molecular Bases of Embryogenesis, IBCh RAS, together with colleagues from the Laboratory of Mathematical Methods and Models in Bioinformatics, IPPI RAS developed a bioinformatics method that allows one to reveal genes that appear or disappear at a certain stage of evolution. Using this method, a number of genes were found that disappeared in warm-blooded animals, including humans. For further study, one of the found genes was selected that encodes a previously unknown protein. Using the example of this gene, the validity of the hypothesis about the role of disappeared genes in the progressive development of the brain and in the loss of regenerative ability in warm-blooded animals was confirmed. Also this transmembrane protein (c-Answer) is the new FGF and ADP signaling modulator. The results are published in Cell Reports. Learn more