Laboratory of biocatalysis
Laboratory of biocatalysis was founded in 1997. Two major projects developing in the Laboratory that became a continuation of the Professor Gabibov’s pioneering work.
The first group that maintained by Ivan Smirnov continues to study a classic "abzimology" but a qualitatively new level. It is looking for a balance between combinatorial methods and rational design to create proteins with predetermined properties de novo. Recently the group developes the microfluidic technologies for multi-parameter screening of biocatalysts clones and cells in general.
The second team maintained by Alexey Belogurov studying the molecular basis of autoimmune processes with an emphasis in autoimmune neurodegeneration. Basically, on the agenda is a chronic demyelinating disease of the central nervous system — multiple sclerosis, and also a neurodegeneration and peripheral nervous system — Guillain-Barré syndrome. The Laboratory developes screening technology, such as yeast, phage and lentiviral displays (Tatyana Bobik participates in this work).
Early significant advances in biotechnology have been achieved in the laboratory such as expression of proteins, for example, blood factors, antibodies in prokaryotic systems and in cell line CHO. A huge contribution to the study made by professor Natalia Ponomarenko.
The laboratory has a wide range of partners both at the Institute and beyond. In collaboration with the Laboratory of Proteomics researchers study multiple sclerosis and Guillain-Barre syndrome, they workes on the creation of immunotoxins with the Laboratory of Protein Engineering and the Laboratory of Molecular Immunology, also they conduct the study of ion channels in autoreactive lymphocytes together with the Molecular Instruments for Neurobiology Group.
In addition, the Laboratory cooperates with the European Molecular Biology Laboratory in Hamburg, the Institute of Physical-Chemical Medicine, the Center of Nanotechnology of Russian Academy of Sciences, the Institute of Chemical Biology and Fundamental Medicine of Russian Academy of Sciences, SRP "Bioclinicum" and A.N. Belozersky Institute of Physico-Chemical Biology Moscow State University. The Laboratory keeps a good relationship with several prominent figures such as Nobel laureates Aaron Ciechanover and Sidney Altman, a former president of the Scripps Research Institute, and a father of modern abzimology Richard Lerner etc.
A personalised approach for treating T-cell malignancies (2019-12-06)
Efficient and specific removal of malignant cells is the ultimate goal of cancer therapy. The current rapid development of chimeric antigen receptor T cell (CAR-T cell or CART) therapy potentially provides high efficiency and allows long-term surveillance, which have greatly extended the frontier of leukemia treatment. We validated the idea of using CARTs as targeting agents and observed excellent continuous efficacy as well as specificity. Combining CDR3 targeting with the CART approach provides a solution for a substantial portion of patients with T cell leukemia and lymphoma, with supposedly minimized side effects. After validation of this strategy to eliminate pathological T cells ex vivo and in vivo, we envisage this approach as a generally useful alternative and supplement to the popular approach of common antigen targeting to treat T cell malignancies, especially considering its safety.
- (2019). Unique CDR3 epitope targeting by CAR-T cells is a viable approach for treating T-cell malignancies. Leukemia 33 (9), 2315–2319
Personalized therapy of B-cell lymphomas (2018-11-30)
We report the development of a novel platform to significantly enhance the efficacy and safety of Follicular lymphoma treatment. Since lymphoma is a clonal malignancy of a diversity system every tumor has a different antibody on its cell surface. Combinatorial autocrine-based selection is used to rapidly identify specific ligands for these B cell receptors on the surface of FL tumor cells. The selected ligands are used in a CAR-T format for redirection of human CTLs. Science Advances 2018. Stepanov AV,...,Gabibov AG, Lerner RA
- (2018). Autocrine-based selection of ligands for personalized CAR-T therapy of lymphoma. Sci Adv 4 (11), eaau4580
Oral microbiome of Siberian bear as a source of new antibiotics c (2018-11-30)
A new pipeline for antibiotic discovery using microfluidic screening technologies has been proposed. The biosynthetic pathways of the new antibiotic amicoumacin has been discovered. Specific enzymes: kinase and phosphatase, responsible for the inactivation and activation of the antibiotic were found
- (2018). Ultrahigh-throughput functional profiling of microbiota communities. Proc Natl Acad Sci U S A 115 (38), 9551–9556