Laboratory of molecular immunology

Department of immunology

Head: Sergey Deev, corresponding member of the academy of sciences

Sergey Deev, corresponding member of the academy of sciencesdepart.
Galina Proshkina, Ph.D.s. r. f.+7(499)724-71-88
Ekaterina Lebedenko, Ph.D.s. r., +7(926)2417030, +7(499)1510178
Aleksej Shul'ga, Ph.D.s. r.
Ekaterina Souslova, Ph.D.r.
Yuri Khodarovichr.
German Kagarlitskiyj. r.
Elena Shramova, Ph.D.j. r.
Oleg Stremovskijj. r.
Taras Balandinj. r. f.+7(495)330-63-92
Sergej Lukashj. r. f.+7()3306392
Kristina Mironovaj. r.
Maxim Nikitin, Ph.D.j. r.
Tatiana Zdobnova, Ph.D.j. r.
Elena KonovalovaPhD
Victoria ShipunovaPhD
Ivan ZelepukinPhD
Dmitrij Karpenkores. eng.
Ol'ga Korol'chukres.

Selected publications

  1. Generalova A.N., Kochneva I.K., Khaydukov E.V., Semchishen V.A., Guller A.E., Nechaev A.V., Shekhter A.B., Zubov V.P., Zvyagin A.V., Deyev S.M. (2015). Submicron polyacrolein particles in situ embedded with upconversion nanoparticles for bioassay. Nanoscale 7 (5), 1709–17 [+]

    We report a new surface modification approach of upconversion nanoparticles (UCNPs) structured as inorganic hosts NaYF4 codoped with Yb(3+) and Er(3+) based on their encapsulation in a two-stage process of precipitation polymerization of acrolein under alkaline conditions in the presence of UCNPs. The use of tetramethylammonium hydroxide both as an initiator of acrolein polymerization and as an agent for UCNP hydrophilization made it possible to increase the polyacrolein yield up to 90%. This approach enabled the facile, lossless embedment of UCNPs into the polymer particles suitable for bioassay. These particles are readily dispersible in aqueous and physiological buffers, exhibiting excellent photoluminescence properties, chemical stability, and also allow the control of particle diameters. The feasibility of the as-produced photoluminescent polymer particles mean-sized 260 nm for in vivo optical whole-animal imaging was also demonstrated using a home-built epi-luminescence imaging system.

  2. Поляновский О.Л., Лебеденко Е.Н., Деев С.М. (2013). ErbB-онкогены - мишени моноклональных антител. Биохимия 77 (3), 289–311 ID:872
  3. Aghayeva U.F., Nikitin M.P., Lukash S.V., Deyev S.M. (2013). Denaturation-resistant bifunctional colloidal superstructures assembled via the proteinaceous barnase-barstar interface. ACS Nano 7 (2), 950–61 [+]

    To date, a number of biomolecule-mediated nanoparticle self-assembly systems have been developed that are amenable to controllable disassembly under relatively gentle conditions. However, for some applications such as design of self-assembled multifunctional theragnostic agents, high stability of the assembled structures can be of primary importance. Here, we report extraordinarily high durability of protein-assisted nanoparticle self-assembly systems yielding bifunctional colloidal superstructures resistant to extreme denaturing conditions intolerable for most proteins (e.g., high concentrations of chaotropic agents, high temperature). Among the tested systems (barnase-barstar (BBS), streptavidin-biotin, antibody-antigen, and protein A-immunoglobulin), the BBS is notable due to the combination of its high resistance to severe chemical perturbation and unique advantages offered by genetic engineering of this entirely protein-based system. Comparison of the self-assembly systems shows that whereas in all cases the preassembled structures proved essentially resistant to extreme conditions, the ability of the complementary biomolecular pairs to mediate assembly of the initial biomolecule-particle conjugates differs substantially in these conditions.

  4. Nikitin M.P., Zdobnova T.A., Lukash S.V., Stremovskiy O.A., Deyev S.M. (2010). Protein-assisted self-assembly of multifunctional nanoparticles. Proc. Natl. Acad. Sci. U.S.A. 107 (13), 5827–32 [+]

    A bioengineering method for self-assembly of multifunctional superstructures with in-advance programmable properties has been proposed. The method employs two unique proteins, barnase and barstar, to rapidly join the structural components together directly in water solutions. The properties of the superstructures can be designed on demand by linking different agents of various sizes and chemical nature, designated for specific goals. As a proof of concept, colloidally stable trifunctional structures have been assembled by binding together magnetic particles, quantum dots, and antibodies using barnase and barstar. The assembly has demonstrated that the bonds between these proteins are strong enough to hold macroscopic (5 nm-3 microm) particles together. Specific interaction of such superstructures with cancer cells resulted in fluorescent labeling of the cells and their responsiveness to magnetic field. The method can be used to join inorganic moieties, organic particles, and single biomolecules for synergistic use in different applications such as biosensors, photonics, and nanomedicine.

  5. Zdobnova T.A., Dorofeev S.G., Tananaev P.N., Vasiliev R.B., Balandin T.G., Edelweiss E.F., Stremovskiy O.A., Balalaeva I.V., Turchin I.V., Lebedenko E.N., Zlomanov V.P., Deyev S.M. (2009). Fluorescent immunolabeling of cancer cells by quantum dots and antibody scFv fragment. J Biomed Opt 14 (2), 021004 [+]

    Semiconductor quantum dots (QDs) coupled with cancer-specific targeting ligands are new promising agents for fluorescent visualization of cancer cells. Human epidermal growth factor receptor 2/neu (HER2/neu), overexpressed on the surface of many cancer cells, is an important target for cancer diagnostics. Antibody scFv fragments as a targeting agent for direct delivery of fluorophores offer significant advantages over full-size antibodies due to their small size, lower cross-reactivity, and immunogenicity. We have used quantum dots linked to anti-HER2/neu 4D5 scFv antibody to label HER2/neu-overexpressing live cells. Labeling of target cells was shown to have high brightness, photostability, and specificity. The results indicate that construction based on quantum dots and scFv antibody can be successfully used for cancer cell visualization.

  6. Schulga A.A., Mechev P.V., Kirpichnikov M.P., Skryabin K.G., Deyev S.M. (2009). Construction of the plasmid-free strain for human growth hormone production. Biochimie 128-129, 148–53 [+]

    The E. coli strain, overproducing human growth hormone (hGH) was made by integration of the hGH gene under the control of T7 promoter into the chromosomal LacZ gene of BL21(DE3) via lambda Red recombineering. The strain gave higher productivity (50 mg·L(-1)·OD550(-1)) and better growth characteristics than the corresponding strain in which the same hGH expression cassette was placed in a plasmid. The protein produced by the plasmid-free strain was purified and characterized to be hGH. The results demonstrates that a plasmid-free recombinant strain having a single-copy gene expression cassette in the chromosome could provide better gene activity regulation, higher productivity, superior growth characteristics, as well as more stringent control of the gene sequence invariance than a plasmid-based strain.

  7. Deyev S.M., Lebedenko E.N. (2008). Multivalency: the hallmark of antibodies used for optimization of tumor targeting by design. Bioessays 30 (9), 904–18 [+]

    High-precision tumor targeting with conventional therapeutics is based on the concept of the ideal drug as a "magic bullet"; this became possible after techniques were developed for production of monoclonal antibodies (mAbs). Innovative DNA technologies have revolutionized this area and enhanced clinical efficiency of mAbs. The experience of applying small-size recombinant antibodies (monovalent binding fragments and their derivatives) to cancer targeting showed that even high-affinity monovalent interactions provide fast blood clearance but only modest retention time on the target antigen. Conversion of recombinant antibodies into multivalent format increases their functional affinity, decreases dissociation rates for cell-surface and optimizes biodistribution. In addition, it allows the creation of bispecific antibody molecules that can target two different antigens simultaneously and do not exist in nature. Different multimerization strategies used now in antibody engineering make it possible to optimize biodistribution and tumor targeting of recombinant antibody constructs for cancer diagnostics and therapy.


Sergey Deev