Institute of
bioorganic chemistry

Tumor-infiltrating B-cells play important roles in tumor microenvironmet. Scientists from the Genomics of adaptive immunity department IBCh RAS demonstarted that high IgG1/IgA ratio is an important prognostic indicator for several subtypes of bladder cancer, in which it is also associated with the prominence of a cytotoxic gene signature. To achieve better prognostic and predictive value, authors normalized cytotoxic signature against the extent of immune cell infiltration. Developed PRIMUS model which integrated the normalized cytotoxic, as well as B- and NK-cell signatures, allowed highly accurate prediction of response to anti-PD-L1 immunotherapy. The work is published in Cancer Immunology Research.

Cell therapy based on genetically modified NK cells is a promising strategy for cancer treatment, but the heterogeneity of NK cells limits the possibilities of this approach. The team from the Laboratory of Cell Interactions IBCh RAS demonstrated differences of NK cell subsets in susceptibility to retroviral transduction of the inducible caspase 9 (iCasp9) gene, the insertion of which can allow timely and rapid triggering of iCasp9-NK cell apoptosis with the addition of a special inductor in case of their excessive hyperactivity. The highest transduction efficiency was shown for the CD57–KIR2DL2/3+NKG2C+ NK cell subset, which was distinguished by an increased proliferative potential and an increased expression level of the HLA-DR activation marker. At the same time, among the iCasp9 populations, KIR2DL2/3+ NK cells responded most weakly to the apoptosis induction. The work is published in the International Journal of Molecular Sciences.

Scientists from the Queensland University of Technology and the University of Queensland (Australia), with the participation of a member of the group of molecular tools for living system studies (IBCH), have developed a method that allows folding in vitro produced disulfide-rich peptides and proteins in an aggregation-free and thermodynamically controlled folding environment. To this end, we modify an E. coli-based in vitro translation system to allow co-translational capture of translated products by affinity matrix. This approach reduces aggregation of (poly) peptides and provides efficient oxidative folding under thermodynamic control. The developed approach can find application for prototyping a wide range of disulfide-constrained peptides, macrocyclic peptides with unnatural bonds, and antibody fragments in amounts sufficient for interaction analysis and biological activity assessment. The work was published in Nature Communications journal (IF 14.919).

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. Learn more

Telomerase RNA is one of the core components of the telomerase complex and participates in survival mechanisms that are activated under stress conditions. Human telomerase RNA protein (hTERP) is encoded by telomerase RNA and has been recently shown to be involved in autophagy regulation. In this studya team of scientists from the Laboratory of Molecular Oncology of the IBCh RAS, MSU, and SRI PCM FMBA of Russia demonstrated the role of hTERP in the modulation of signaling pathways regulating autophagy, protein biosynthesis, and cell proliferation. The AMPK signaling pathway was affected in cells deficient of hTERP and when hTERP was overexpressed. The appearance of hTERP is important for metabolism switching associated with the accelerated proliferation of cells in healthy and pathological processes. These findings demonstrate the connection between telomerase RNA biogenesis and function and signaling pathways. The results are published in the Frontiers in Cell and Developmental Biology journal.