Laboratory for the Development of Innovative Drugs and Agricultural Biotechnology

The lab conducts both fundamental and applied research including search and validation of new targets and new approaches for the development of new drugs and plant protection methods. High-content screening and analysis of live cell digital images compose basic technological platform for fundamental research on aging and age-related pathologies, preclinical studies of drug candidates against various diseases including carcinogenesis, inflammation, Alzheimer’s and Parkinson’s diseases. There are two Doctors of Sciences and seven PhDs working in the lab.

Fields of research

There are four main directions of research in the lab: oncology, active longevity and age-related neurodegenerative diseases, agricultural biotechnologies, and phagotherapy. One of the key ideas is development of competitive domestic pharmaceuticals with detailed functional characteristic its biological effects on different aspects pro- and eukaryotic cell’ vital functions.

Projects

Oncology

  1. Executing of preclinical research cycle in context of current State Contract No. 14.N08.11.0122 on “Preclinical studies of low-molecular compound based on inhibitor of BRAF enzyme for metastatic melanoma therapy.”

  2. Search of new photosensitizers for effective use in photodynamic anticancer therapy. Evaluation of photosensitive activity of new drugs developed on nematodes Caеnorhabditis elegans (C. elegance) as in vivo model.

  3. Molecular and physical-chemical heterogeneity of tumor exosomes (oncosomes) and its regulation value — next generation cancer diagnostics.

  4. Joint research project on investigation of new specific tumor invasion mechanisms and drug discovery to combat dissemination of cancer cells  (in collaboration with professor Alexis Gautreau, laboratory visiting professor and Principal Investigator at CNRS, Professor at Ecole Polytechnique, Chair of the Biology Dept, Ecole Polytechnique, Paris (France).

  5. Joint research project on the discovery of innovative drug based on tankyrase activity inhibitor for therapy of solid tumors (in collaboration with professor Stefan Krauss (University of Oslo, Norway).

Active longevity

  1. Development of 3-D analysis program for biological images and algorithms of aging dynamic estimation on nematodes C. elegance model. Algorithm is based on computer program for measuring physical properties of live nematodes C. elegance acquired in real-time mode. Development of this program allows to accelerate analysis of longevity experimental results and get biological information about test subjects.

  2. Research on the effect of different compounds extracted from natural vegetable and animal sources on longevity  of short-living invertebrate (nematodes C. elegance) and vertebrates (Nothobranchius N.furzeri fish). Acquired data allow to identify new signaling pathways and pick the most perspective substrates for subsequent development of geroprotectors for prolongation and quality improvement of human life.

  3. Research on signalling pathways and factors influencing DNA repair through aging and under impact of different physical factors.

Agricultural biotechnologies

  1. Development of methods and means for decomposing of mycotoxins accounting for agricultural animals being in danger including swines, poultry and cattle, which are widespread in the Russian Federation.

  2. Investigation of new growth regulators for agricultural plants based on lab-developed model systems of Tobacco (Nicotiana tabacum L.) pollen, and cyanobacterias (Chlorella vulgaris), using automatic High Content screening system platform ImageXpress Micro XL (Molecular Devices, USA).

  3. Validation of biological activity and mechanism of action of new perspective growth modulators for agricultural plants in vivo during the whole development cycle in collaboration with Prof. Dr. K. Palme (University of Freiburg, Germany).

Phagotherapy

  1. Investigation of bacteriophages  to combat microbial pathogens in food and fish processing.

  2. Pharmacological evaluation of bacteriophages’ therapeutic effect against microbial pathogens resistant to antibiotics.

  3. Study of bacteriophages’ antimicrobial effect against hypermucoid starins of  Klebsiella pneumoniae resistant to antibiotics.

  4. Study in vitro and in vivo of RNA polymerase inhibitors encoded in genomes of bacteriophages infecting Acinetobacter baumannii.

Identifying and cloning of genes of structural depolymerases forming prophages, which are integrated in chromosomal DNA of different A.baumannii strains for gaining recombinant proteins with exopolysaccharide-depolymerisation activity.

Sergey Leonov

Head of the Lab

Education
MD, PhD
Professional experience
CSO,  School of Biological and Medical Physics and Life Sciences Center of MIPT
Academic Interests
Publications

2017, Methods in Molecular Biology

Method for ultra-rapid high-content screening for biologically active chemicals using plant pollen

2016, Current Topics in Medicinal Chemistry (3.402)

In silico approaches to the design of NS5A inhibitors

2016, Moscow University Chemistry Bulletin (0.88)

2011, Journal of Biological Chemistry

RAGE prevents endothelial cell membrane resealing and regulates F-actin remodeling in a beta-catenin dependent manner

Roman Chuprov-Netochin

Researcher

Education
PhD in biology
Professional experience
Chuprov-Netochin is an expert in the development of innovative pharmaceutical drugs with the use of high-efficiency phenotypic screening platform on the latest device ImageXpress Micro XL (manufactured by Molecular Devices, USA). In the period from 2006 to 2009, he was a postgraduate student at the Institute of Bioorganic Chemistry named after M.M. Shemyakin and Y.A. Ovchinnikov of the Russian Academy of Sciences in the Laboratory of Molecular Bioengineering. His thesis work was devoted to the development of the technology for production of recombinant fibrillar proteins of T4 bacteriophage. He deeply studied a structural biology, particularly the tail fibrils folding mechanisms, he was also engaged in the crystallization of the chimeric phage proteins.
Academic Interests
Publications

2017, Methods in Molecular Biology

Method for ultra-rapid high-content screening for biologically active chemicals using plant pollen

2011, Russian Journal of Biopharmaceuticals

Peptidyl-prolyl isomerase SLyD controls the recombinant folding of bacteriophage Т4 long tail fiber fragments

2010, Acta Crystallographica Section F

X-ray investigation of gene-engineered human insulin crystallized from a solution containing polysialic acid

Elena Marusich

Deputy head

Education
PhD in biology
Publications

2017, Methods in Molecular Biology

Method for ultra-rapid high-content screening for biologically active chemicals using plant pollen

2016, Moscow University Chemistry Bulletin (0.88)

2014, Kainic acid: neurotoxic properties, biological sources and clinical applications

Expression of GluR6, a kainate Receptor, in Human Lymphocytes

2012, Alcohol

Ethanol Protects from Injury due to Ischemia and Reperfusion by Increasing Vascularity via Vascular Endothelial Growth Factor

2011, Journal of the Neurological Sciences

Lymphocyte Adhesion to CCR5 Ligands is Reduced by Anti-CCR5 Gene Delivery

2011, Gene Therapy

Gene Transfer to the Rhesus Monkey Brain Using SV40-derived Vectors is Durable and Safe

2010, Nature Methods

Efficient CNS Gene Delivery by Intravenous Injection

2010, The FASEB Journal

Role of CCR5 and its Ligands in the Control of Vascular Inflammation and Leukocyte Recruitment Required for Acute Excitotoxic Seizure Induction and Neural Damage

Elena Petersen

Principal researcher

Education
PhD in biology
Publications

2017, Clinical Lymphoma, Myeloma and Leukemia (2.494)

Non-Covalent Conjugation of Antibodies and Lentiviruses to Nanoparticles as a Potential Tool for Gene Therapy

Stanislav Biryukov

Senior researcher

Education
ScD in physics and mathematics

Vasiliy Chernyshov

Researcher

Education
PhD in engineering

Alexey Belikov

Junior researcher

Education
PhD in biology
Publications

Alina Smirnova

Junior researcher

Georgiy Bombin

Engineer

Evgenia Malysheva

Lab assistant

Irina Pozhidaeva

Lab assistant

2017

Journal of Medicinal Chemistry (6.259)

Discovery of a Novel Series of Tankyrase Inhibitors by a Hybridization Approach

U. R. Anumala, J. Waaler, Y.Nkizinkiko, A. Ignatev, K.Lazarow, P. Lindemann, P. A.Olsen, S. Murthy, E.Obaji, A. G. Majouga, S. Leonov, J. P. von Kries, L. Lehtiö, S. Krauss, and M.Nazaré

Moscow Institute of Physics and Technology

Viruses (3.465)

Novel Fri1-like Viruses Infecting Acinetobacter baumannii-vB_AbaP_AS11 and vB_AbaP_AS12-Characterization, Comparative Genomic Analysis, and Host-Recognition Strategy

Popova A.V., Lavysh D.G. Klimuk E.I., Edelstein M.V., Bogun A.G., Shneider M.M., Goncharov A.E., Leonov S.V., Severinov K.V.

Moscow Institute of Physics and Technology

Carbohydrate Research (2.096)

Structures of the K35 and K15 capsular polysaccharides of Acinetobacter baumannii LUH5535 and LUH5554 containing amino and diamino uronic acids

Shashkov A.S., Liu B., Kenyon J.J., Popova A.V., Shneider M.M., Senchenkova S.N., Arbatsky N.P., Miroshnikov K.A., Wang L., Knirel Y.A.

Moscow Institute of Physics and Technology

International Journal of Biological Macromolecules (3.671)

Acinetobacter baumannii K11 and K83 capsular polysaccharides have the same 6-deoxy-l-talose-containing pentasaccharide K units but different linkages between the K units

Kenyon J.J., Shashkov A.S., Senchenkova S.N., Shneider M.M., Liu B., Popova A.V., Arbatsky N.P., Miroshnikov K.A., Wang L., Knirel Y.A., Hall R.M.

Moscow Institute of Physics and Technology

Microbiology (2.159)

The KL24 gene cluster and a genomic island encoding a Wzy polymerase contribute genes needed for synthesis of the K24 capsular polysaccharide by the multiply antibiotic resistant Acinetobacter baumannii isolate RCH51

Kenyon J.J., Kasimova A.A., Shneider M.M., Shashkov A.S., Arbatsky N.P., Popova A.V., Miroshnikov K.A., Hall R.M., Knirel Y.A.

Moscow Institute of Physics and Technology

Scientific Reports (4.259 )

The number of key carcinogenic events can be predicted from cancer incidence

Belikov AV

Moscow Institute of Physics and Technology

Frontiers in Pharmacology (4.400)

The evaluation of geroprotective effects of selected flavonoids in Drosophila melanogaster and Caenorhabditis elegans

E. Lashmanova, N. Zemzkaya, E. Proshkina, A. Kudryavtzeva, M. Voloshkina, E. Marusich, S. Leonov, A. Zhavoronkov, A. Moskalev

Moscow Institute of Physics and Technology

The FEBS Journal (3.902 )

Discovery of geroprotective capacity of human placental preparation on Caenorhabditis elegans model

E. Marusich, S. Leonov, E. Dibrova

Moscow Institute of Physics and Technology

Methods in Molecular Biology

Method for ultra-rapid high-content screening for biologically active chemicals using plant pollen

E. Marusich, R. Chuprov-Netochin, Y. Neskorodov, Y. Mishutkina, P. Volynchuk, S. Leonov, Y. Ivanenkov, A. Turaev, K. Palme

Moscow Institute of Physics and Technology

Aging (Albany NY) (4.87 )

Diffuse colonies of human skin fibroblasts in relation to cellular senescence and proliferation

Zorin V., Zorina A., Smetanina N., Kopnin P., Ozerov I.V., Leonov S., Isaev A., Klokov D., Osipov A.N.

Moscow Institute of Physics and Technology

Oncotarget (5.17 )

γH2AX, 53BP1 and Rad51 protein foci changes in mesenchymal stem cells during prolonged X-ray irradiation

A. Tsvetkova, I.V. Ozerov, M. Pustovalova, A. Grekhova, P. Eremin, N. Vorobyeva, I. Eremin, A. Pulin, V. Zorin, P. Kopnin, S. Leonov, A. Zhavoronkov, D. Klokov, A.N. Osipov

64317-64329 page

Moscow Institute of Physics and Technology

Aging (Albany NY) (4.87)

Residual γH2AX foci induced by low dose x-ray radiation in bone marrow mesenchymal stem cells do not cause accelerated senescence in the progeny of irradiated cells

Pustovalova M, Astrelina ТA, Grekhova A, Vorobyeva N, Tsvetkova A, Blokhina T, Nikitina V, Suchkova Y, Usupzhanova D, Brunchukov V, Kobzeva I, Karaseva Т, Ozerov IV, Samoylov A, Bushmanov A, Leonov S, Izumchenko E, Zhavoronkov A, Klokov D, Osipov AN

Moscow Institute of Physics and Technology

Clinical Lymphoma, Myeloma and Leukemia (2.494)

Non-Covalent Conjugation of Antibodies and Lentiviruses to Nanoparticles as a Potential Tool for Gene Therapy

A.Petukhov, K.Shevchenko, A. Daks, T. Leonova, A. Titov, E. Smirnov, E. Zaikova, E. Petersen, D. Motorin, A. Zaritskey, M. Nikitin

S394–S395 page

Moscow Institute of Physics and Technology

Clinical Therapeutics (2.947)

2016

Aging (Albany NY) (3.979)

Accumulation of spontaneous γH2AX foci in long-term cultured mesenchymal stromal cells

M. Pustovalova, A.Grekhova, Т. Astrelina, V. Nikitina, E. Dobrovolskaya, Y. Suchkova, I. Kobzeva, D.Usupzhanova, N.Vorobyeva, A.Samoylov, A. Bushmanov, I. V. Ozerov, A. Zhavoronkov, S. Leonov, D. Klokov, A. N. Osipov

Moscow Institute of Physics and Technology

BMC Plant Biology (4.085)

Novel small molecule modulators of plant growth and development identified by high-content screening with plant pollen

R. Chuprov–Netochin, Y.Neskorodov, E. Marusich, Y. Mishutkina, P. Volynchuk, S. Leonov, K. Skryabin, A. Ivashenko, K. Palme and A. Touraev

Moscow Institute of Physics and Technology

Journal of Natural Products (3.798 )

Efficient Synthesis of Glaziovianin A Isoflavone Series from Dill and Parsley Extracts and Their in Vitro/in Vivo Antimitotic Activity

V. V. Semenov, D. V. Tsyganov, M. N. Semenova, R.N. Chuprov-Netochin, M. M. Raihstat, L. D. Konyushkin, P. B. Volynchuk, E. I. Marusich, V.V. Nazarenko, S.V. Leonov, and A. S. Kiselyov

Moscow Institute of Physics and Technology

Current Topics in Medicinal Chemistry (3.402)

In silico approaches to the design of NS5A inhibitors

Y. A. Ivanenkov, M. S. Veselov, V. A. Aladinskiy, A.G. Shakhbazyan, S. M. Yartseva, A. G. Majouga, A. V. Aladinskaya , A. S. Vantskul, S. V. Leonov and A. V. Ivachtchenko

Moscow Institute of Physics and Technology

Glycobiology (3.283)

Acinetobacter baumannii K27 and K44 capsular polysaccharides have the same K unit but different structures due to the presence of distinct wzy genes in otherwise closely related K gene clusters

Shashkov AS, Kenyon JJ, Senchenkova SN, Shneider MM, Popova AV, Arbatsky NP, Miroshnikov KA, Volozhantsev NV, Hall RM, Knirel YA

Moscow Institute of Physics and Technology

Moscow University Chemistry Bulletin (0.88)

High throughput screening platform for new inhibitors of protein biosynthesis

P. V. Sergiev, I. A. Osterman, A. Y. Golovina, E. S. Andreyanova, I. G. Laptev, F. I. Pletnev, S. A. Evfratov, E. I. Marusich, M. S. Veselov, S. V. Leonov, Y. A. Ivanenkov, A. A. Bogdanov, and O. A. Dontsova

Moscow Institute of Physics and Technology

2015

Carbohydrate Research (1.451)

Structure of the neutral capsular polysaccharide of Acinetobacter baumannii NIPH146 that carries the KL37 capsule gene cluster

Arbatsky NP, Shneider MM, Kenyon JJ, Shashkov AS, Popova AV, Miroshnikov KA, Volozhantsev NV, Knirel YA

Moscow Institute of Physics and Technology

Phytochemistry (3.35)

Computational insight into the chemical space of plant growth regulators

N.A. Bushkov, N. V. Chufarova, M.S. Veselov, A.G. Majouga, D.V. Shumilina, P. B. Volynchuka, R. N. Chuprov-Netochin, E.I. Marusich, S. V. Leonov, Y. A. Ivanenkov

254-264 page

Moscow Institute of Physics and Technology

Pharmacological Research (4.408)

Fucoxanthin increases lifespan of Drosophila melanogaster and Caenorhabditis elegans

E. Lashmanova, E.Proshkina,S. Zhikrivetskaya, O.Shevchenko, E. Marusich, S. Leonov, A. Melerzanov, A.Zhavoronkov, A. Moskalev

228–241 page

Moscow Institute of Physics and Technology

2014

Neurobiology of Learning and Memory (3.652)

Immunization with either prion protein fragment 95-123 or the fragment-specific antibodies rescue memory loss and neurodegenerative phenotype of neurons in olfactory bulbectomized mice

Bobkova N.V., Medvinskaya N.I., Kamynina A.N., Aleksandrova I.Y., Nesterova I.V., Samokhin A.V., Koroev D.O., Filatova M.P., Nekrasov P.V., Abramov A.Y., Leonov S.V., Volpina O.M.

50–64 page

Moscow Institute of Physics and Technology

Kainic acid: neurotoxic properties, biological sources and clinical applications

Expression of GluR6, a kainate Receptor, in Human Lymphocytes

Marusich, E., Louboutin, J.P., Strayer, D.S.

Moscow Institute of Physics and Technology

2011

Journal of Biological Chemistry

RAGE prevents endothelial cell membrane resealing and regulates F-actin remodeling in a beta-catenin dependent manner

F.Xiong, S.Leonov, A. C. Howard, S. Xiong, B. Zhang, L. Mei, P. McNeil, S. Simon and W-C. Xiong

35061-35070 page

Moscow Institute of Physics and Technology

Journal of the Neurological Sciences

Lymphocyte Adhesion to CCR5 Ligands is Reduced by Anti-CCR5 Gene Delivery

Marusich, E., Louboutin, J.P, Checkmasova, A.A, Strayer, D.S.

25-27 page

Moscow Institute of Physics and Technology

Gene Therapy

Gene Transfer to the Rhesus Monkey Brain Using SV40-derived Vectors is Durable and Safe

Louboutin, J.P., Marusich, E., Fischer-Perkin, J., Dufour, J.P., Bunnell, B.A., Strayer, D.S.

1-10 page

Moscow Institute of Physics and Technology

Russian Journal of Biopharmaceuticals

Peptidyl-prolyl isomerase SLyD controls the recombinant folding of bacteriophage Т4 long tail fiber fragments

R. N. Chuprov-Netochin, S. V. Amarantov, M. M. Shneider, N. N. Sykilinda, M. V. Filchikov, M. A. Ivanova, V. V. Mesyanzhinov, K. A. Miroshnikov

30-36 page

Moscow Institute of Physics and Technology

2009

Alzheimers & Dementia

The Abeta Oligomer Selective Antibody Nab61 Recognizes Abeta Oligomers In The AD And APP Transgenic Mouse Brains And Neutralizes Abeta Mediated Synaptic Dysfunction

J. Lundkvist, L. M. Kim, E. Gustafsson, E. Hagström, H. Zetterberg, E. Hanse, G. Von Euler, S. Leonov, J. Näslund, C. Dahlqvist, J. Q. Trojanowski, V. M.-Y. Lee

Moscow Institute of Physics and Technology

2012

Alcohol

Ethanol Protects from Injury due to Ischemia and Reperfusion by Increasing Vascularity via Vascular Endothelial Growth Factor

Louboutin, J.P., Marusich, E., Gao, E., Agrawa, L., Koch, W.J., Strayer, D.S.

1-14 page

Moscow Institute of Physics and Technology

2010

Nature Methods

Efficient CNS Gene Delivery by Intravenous Injection

Louboutin, J.P., Chekmasova, A.A., Marusich, E., Chowdhury, J.R., Strayer, D.S.

905-907 page

Moscow Institute of Physics and Technology

The FASEB Journal

Role of CCR5 and its Ligands in the Control of Vascular Inflammation and Leukocyte Recruitment Required for Acute Excitotoxic Seizure Induction and Neural Damage

Louboutin, .J, Checkmasova, A., Marusich, E., Agrawal, L., Strayer, D.S.

737-753 page

Moscow Institute of Physics and Technology

Brain Research

Dopaminergic Neurotoxicity of HIV-1 gp120: Reactive Oxygen Species as Signaling Intermediates

Agrawal, L., Louboutin, J.P., Marusich, E., Reyes, B.A., Van Bockstaele, E.J., Strayer, D.S.

Moscow Institute of Physics and Technology

Acta Crystallographica Section F

X-ray investigation of gene-engineered human insulin crystallized from a solution containing polysialic acid

Timofeev VI, Chuprov-Netochin RN, Samigina VR, Bezuglov VV, Miroshnikov KA, Kuranova IP.

Moscow Institute of Physics and Technology

The Buck Institute for Research on Aging
Novato

Caenorhabditis Genetics Center (CGC)
Minneapolis

University of Amsterdam
Amsterdam

Heinrich-Heine-University Düsseldorf
Düsseldorf

Lomonosov Moscow State University (MSU)

Bauman Moscow State Technical University

Northern State Medical University

Altai State University

The University of Luxembourg

University of Oslo, Norway

University of Freiburg, Germany

University of Amsterdam Science, Netherlands

The Komi Biology Institute of the Scientific Center of the Ural Department of the Russian Academy of Sciences
Syktyvkar

Institute of Cell Biophysics of the Russian Academy of Sciences
Pushchino

ChemRar High-Tech Center
Khimki

M.M. Shemyakin and Y.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences
Moscow

S.N. Vinogradsky Institute of Microbiology of the Russian Academy of Sciences
Moscow

Federal State Institution of Science State Research Center for Applied Microbiology and Biotechnology
Obolensk, Serpukhov district, Moscow region

Institute of Cytology and Genetics of The Siberian Branch of the Russian Academy of Sciences (RAS)

Semenov Institute of Chemical Physics, RAS

Herzen Moscow Oncological Research Institute

Research Center of Biotechnology, RAS

Zelinskiy Institute of Organic Chemistry, RAS

Bach Institute of Biochemistry, RAS

Kapitsa Phystech Lyceum

Luxembourg Centre for Systems Biomedicine

BIOC - CNRS UMR7654, Ecole Polytechnique, France

Caenorhabditis Genetics Center, University of Minnesota, USA

Federal State Scientific-Industrial Company MICROGEN of the Ministry of Healthcare of the Russian Federation
Moscow

TechnoNICOL Corporation

RHANA Medical Corporation

FORT Biopharmaceutical Company of the Russian Ministry of Health

Helmholtz Institute of Pharmacology
Berlin