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Invited researcher Evgeniy Alexandrovich Nudler
Contract number
14.Z50.31.0014
Time span of the project
2014-2018

As of 30.01.2020

43
Number of staff members
64
scientific publications
3
Objects of intellectual property
General information

Name of the project: New approaches in research of regulation of aging and neurodegeneration processes in model organisms

Strategy for Scientific and Technological Development Priority Level: в


Goals and objectives

Research directions: Identifying and characterizing new genes and metabolic paths that control aging and neurodegeneration

Project objective: Investigating molecular mechanisms of aging and neurodegeneration


The practical value of the study

  • For the first time we have shown that not only glucose but also a product of its metabolism – glycogen – is responsible for reducing life span of nematodes. The role of AMP-protein kinase (AMPK) in regulating life span of C.elegans has been investigated.
  • We have demonstrated the effect of the natural AICAR nucleotide that increases average life span of C.elegans and D. melanogaster from 9 to 22%. We have proposed a DNA reparation model based on aging shift of RNA polymerase from the location DNA damage with participation of UvrD and DksA protein factors and ppGpp alarmone.
  • Our researchers have shown human recombinant stress protein (Hsp70) positively affects cognitive characteristics of animals (mice) when administered chronically and intranasally. Chronic administration of Hsp70 to both old and young animals reliably increases quality and duration of their lives, and this effect is only observed in males.
  • We have shown that when nematodes of different lines are used analysis of amyloidogenic and toxic qualities of isoAbeta(1-42) and pS8-Abeta(1-42) active in Alzheimer's disease in comparison with native Abeta(1-42) researched isoforms of beta-amyloid interact with endogenous Abeta molecules in a different manner and are able to either accelerate or slowdown their aggregation in organisms of nematodes – as a result modifying neurotoxic effects changing average life span of nematodes.

Implemented results of research: We have obtained three patents for our inventions: «A genetic structure for expression of functionally active stress protein (Hsp70) with mutated glycosylation sites for eukaryotic expression systems», «A geroprotector for model animals», «Genetic structure pHsp70 for expression of the main human stress proteins in milk of transgenic animals».

Education and career development:

  • 1 doctoral dissertation and 7 candidate dissertations have been defended.
  • 7 postgraduates and young scientists from other organizations have completed internships at the Laboratory.

Collaborations:

New York University School of Medicine (USA), National Institutes of Health (USA), Institute of Cell Biology of the Russian Academy of Sciences: joint research and publications

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Popova А.А., Koksharova O.A., Lipasova V.A., Zaitseva J.V., Katkova-Zhukotskaya O.A., Eremina S.Iu., Mironov A.S., Chernin L.S., Khmel I.A.
Inhibitory and Toxic Effects of Volatiles Emitted by Strains of Pseudomonas and Serratia on Growth and Survival of Selected Microorganisms, Caenorhabditis elegans and Drosophila melanogaster. BioMed Research International Article ID 125704 (2014).
Venu K., Epshtein V., Bradley B., Proshkin S., Mironov A., Cashel M., Nudler E.
ppGpp Couples Transcription to DNA Repair in E.coli. Science 352 (6288): 993–996 (2016).
Gusarov I., Pani B., Gautier L., Smolentseva O., Eremina S., Shamovsky I., Katkova-Zhukotskaya O., Mironov A., Nudler E.
Glycogen Controls Caenorhabditis elegans Lifespan and Resistance to Oxidative Stress. Nature Communication 8: 15868 (2017).
Bobkova N.V., Evgen’ev M.В., Garbuz D.G., Kulikov A.M., Morozov A., Samokhin A., Velmeshev D., Medvinskaya N., Nesterova I., Pollock A., Nudler E.
Exogenous Hsp70 Delays Senescence and Improves Cognitive Function in Aging Mice. Proceedings of the National Academy of Sciences (USA) 112(52): 16006–16011 (2015).
Shilova V.Y., Zatsepina O.G., Garbuz D.G., Funikov S.Y., Zelentsova E.S., Schostak N.G., Kulikov A.M., Evgen’ev M.B.
Heat Shock Protein 70 from a Thermotolerant Diptera species Provides Higher Thermoresistance to Drosophila larvae than Correspondent Endogenous Gene. Insect Molecular Biology 27(1): 61–72 (2018).
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