Press-room / Digest
Elastic fibers and elastin receptor complex: Neuraminidase-1 takes the center stage
In addition to the "supporting" role, the extracellular matrix (ECM) affects the phenotype and behavior of the cell. The largest structures of ECM are elastic fibers (EF), which are mainly composed of elastin. Elastogenesis is a tightly regulated process involving the sialidase activity of the Neuraminidase-1 (Neu-1), which is part of the elastin receptor. Neu-1 also serves as a sensor of elastin degradation, it is able to regulate the activation of TGF-beta and possibly is involved in remodeling of EFs. The article, published in the journal Matrix Biology, provides an overview of the results of long-term studies of molecular mechanisms of life regulation of elastic fibers, in which Neu-1 plays a key role. A number of important data, in particular, the existence of the membrane-bound form of Neu-1 and its ability to dimerize, was first obtained by the French-Russian research team from the University of Reims and IBCH RAS (Lab. of biomolecular modeling).
Unique CDR3 epitope targeting by CAR-T cells is a viable approach for treating T cell
Researches from the Laboratory of biocatalysis of IBCH RAS in collaboration with the Scripps Research Institute and Xiamen University demonstrated for the first time that targeting the CDR3 regions of malignant T cell clones by cell therapy is a viable approach to eliminate leukemia cells. The study was supported by RSF and published in Leukemia.
New rigid nicotine analogues are potent ligands of nicotinic receptors
Malfunctioning of nicotinic acetylcholine receptors (nAChRs) is observed in various mental and neurodegenerative diseases, therefore, the search and design of nAChR ligands is of particular interest. Researchers from the Department of Molecular Neuroimmune Signalling of IBCH, Russian Academy of Sciences in collaboration with colleagues from the University of Florence (Italy) designed new nicotine analogues and revealed their high affinity for α4β2 and α7 nAChRs using radioligand binding assay. In the electrophysiological and calcium imaging experiments some selected compounds showed α7 and α3β2 agonistic properties, while on the α4β2, compounds 1a and 2a behaved as antagonists. Results of the study are published in Journal of Medicinal Chemistry.
Transcription factor Foxp1 plays important role in Treg
Regulatory T cells (Treg) is subpopulation of T helper lymphocytes which possesses immune suppressive properties. Treg are critical in protection from excessive immune response and autoimmunity. Unique functions of Treg are defined by transcription factor Fop3 that controls Treg-specific expression of genes. Dr. Yury Rubtsov from the Dept. of functioning of living systems in cooperation with colleagues from the Memorial Sloan-Kettering Cancer Center (New York City) studied a role of Foxp3-related protein, Foxp1, specifically in the murine Treg. In the absence of Foxp1, Treg displayed distorted Foxp3 chromatin binding which led to decreased sensitivity of the cells to IL-2 and diminished suppressive capacity. Results of the study are published in Nature Immunology.
Adaptive immune response of identical twins to live vaccine
T-cell receptors (TCRs) play a key role in adaptive immunity. TCR repertoire is very diverse and unique to each individual because it forms in the stochastic DNA recombination process. The group of scientists from the Department of genomics of adaptive immunity in collaboration with ENS (Paris, France) studied TCR repertoires of identical twins after immunization with a live vaccine. In each donor, they identified about a thousand different T-cell clones responding to immunization. Responding clones have almost unique repertoire in each donor with higher overlap in identical twin pairs. The study was supported by RSF and published in Proceedings of the National Academy of Sciences.