Laboratory of Genome Variation | Institute of Molecular Genetics
List of staff
Pasyukova, Elena G., Ph. D., Dr. Sci., Professor of Genetics.
Krementsova Anna V., Ph. D., Researcher.
Pudina Iryna A., technician
Rozovsky Yakov M., Ph. D., Researcher.
Roshina Natalia V., Ph. D., Researcher.
Rybina Olga Y., Ph. D., Researcher.
Symonenko Alexander V., Researcher.
Trostnikov Mikhail V., Ph. D. student.
Tsybul’ko Evgenia A., Researcher.
Veselkina, Ekaterina R., Ph. D. student.
Main directions of research
Since 1999, when the laboratory was organized, the main goal of our research was to reveal genes affecting lifespan and to analyze molecular basis of their effects on lifespan variation in Drosophila melanogaster. Genome-wide screens conducted in our lab in collaboration with Trudy Mackay’s lab (North Carolina State University, USA) allowed us to reveal several dozens of candidate genes, whose participation in the lifespan control was not previously known. We selected several of these candidate genes to further assess molecular basis of their impact on longevity. This research was carried out along several main lines.
1. The first line of our work was aimed to get formal proofs of involvement of the above mentioned candidate genes in lifespan control. We were the first do demonstrate that genes encoding transcription factors involved in neuroblast differentiation and neuron specification affect Drosophila lifespan and identified mutations in these genes that increased longevity by up to 70 percent.
2. The second line of our work was aimed to understand whether there is an association between gene expression and the effects on lifespan and to describe gene by gene interactions on the level of transcription and longevity phenotype. We were the first to demonstrate that embryonic transcription of genes encoding transcription factors affects lifespan of adults.
3. The third line of our work was aimed to assess structural and functional variation of genes encoding neuronal transcription factors and involved in lifespan control in natural populations of Drosophila. We succeeded to demonstrate that a naturally occurring polymorphism at the regulatory regions of neuronal genes is able to provide both a six-fold change in gene transcription and a 25% change in lifespan.
4. The fourth line of our work was aimed to develop a Drosophila model of tauopathies based on the overexpression of GSK3-β, a protein kinase involved in various biological processes including neuroblast differentiation. GSK3-β affects neuronal function, in particular, directly phosphorylates tau. We demonstrated that the level of expression of the gene encoding GSK3-β affects synaptic activity, behavior and lifespan.
5. In addition, substantial part of our work was dedicated to the study of the effects of various chemical agents (such as antioxidants and inhibitors of protein kinases and hystone deacetilases) on the lifespan and aging in Drosophila.
1. The first line of our work was aimed to get formal proofs of involvement of the above mentioned candidate genes in lifespan control. We were the first do demonstrate that genes encoding transcription factors involved in neuroblast differentiation and neuron specification affect Drosophila lifespan and identified mutations in these genes that increased longevity by up to 70 percent.
2. The second line of our work was aimed to understand whether there is an association between gene expression and the effects on lifespan and to describe gene by gene interactions on the level of transcription and longevity phenotype. We were the first to demonstrate that embryonic transcription of genes encoding transcription factors affects lifespan of adults.
3. The third line of our work was aimed to assess structural and functional variation of genes encoding neuronal transcription factors and involved in lifespan control in natural populations of Drosophila. We succeeded to demonstrate that a naturally occurring polymorphism at the regulatory regions of neuronal genes is able to provide both a six-fold change in gene transcription and a 25% change in lifespan.
4. The fourth line of our work was aimed to develop a Drosophila model of tauopathies based on the overexpression of GSK3-β, a protein kinase involved in various biological processes including neuroblast differentiation. GSK3-β affects neuronal function, in particular, directly phosphorylates tau. We demonstrated that the level of expression of the gene encoding GSK3-β affects synaptic activity, behavior and lifespan.
5. In addition, substantial part of our work was dedicated to the study of the effects of various chemical agents (such as antioxidants and inhibitors of protein kinases and hystone deacetilases) on the lifespan and aging in Drosophila.
Publications
- Pasyukova E. G., Vieira C., Mackay T. F. C. Deficiency mapping of quantitative trait loci affecting longevity in Drosophila melanogaster. Genetics, 2000, 156:1129-1146.
- Vieira C., Pasyukova E. G., Zeng Z-B., Hackett J. B., Lyman R. F., Mackay T. F. C. Genotype-environment interaction for quantitative trait loci affecting lifespan in Drosophila melanogaster. Genetics, 2000, 154: 213-227.
- De Luca M., Roshina N. V., Geiger-Thornsberry G. L., Lyman R. F., Pasyukova E. G., Mackay T. F. C. Dopa decarboxylase (Ddc) affects variation in Drosophila longevity. Nature Genetics, 2003, 34:429-433.
- Pasyukova E. G., Nuzhdin S. V., Morozova T. V., Mackay T. F. C. Accumulation of transposable elements in the genome of Drosophila melanogaster is associated with decrease in fitness. J. Heredity, 2004, 95:284-290.
- Pasyukova E. G., Roshina N. V., Mackay T. F. C. Shuttle craft: a candidate quantitative trait gene for Drosophila lifespan. Aging Cell, 2004, 3:297-307.
- Mackay T.F.C., Roshina N.V., Leips J.W., Pasyukova E.G. Complex genetic architecture of Drosophila longevity. 2005. Handbook on the Biology of Ageing, Ed. Masoro E., Austad S. P 181-216.
- Anisimov VN1, Bakeeva LE, Egormin PA, Filenko OF, Isakova EF, Manskikh VN, Mikhelson VM, Panteleeva AA, Pasyukova EG, Pilipenko DI, Piskunova TS, Popovich IG, Roshchina NV, Rybina OY, Saprunova VB, Samoylova TA, Semenchenko AV, Skulachev MV, Spivak IM, Tsybul'ko EA, Tyndyk ML, Vyssokikh MY, Yurova MN, Zabezhinsky MA, Skulachev VP. Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 5. SkQ1 prolongs lifespan and prevents development of traits of senescence. Biochemistry (Mosc)., 2008, 73:1329-1342.
- Skulachev V. P., Anisimov V. N., Antonenko Y. N., Bakeeva L. E., Chernyak B. V., Erichev V. P., Filenko O. F., Kalinina N. I., Kapelko V. I., Kolosova N. G., Kopnin B. P., Korshunova G. A., Lichinitser M. R., Obukhova L. A., Pasuykova E. G., Pisarenko O. I., Roginsky V. A., Ruuge E. K., Senin I. I., Severina I. I., Skulachev M. V., Spivak I. M., Tashlitsky V. N., Tkachuk V. A., Vyssokikh M. Yu., Yaguzhinsky L. S., Zorov D. B. An attempt to prevent senescence: a mitochondrial approach. BBA Bioenergetics, 2009, 1787: 437-461.
- Tsybul’ko E. A., Roshina N. V., Rybina O. Y., Pasyukova E. G. Mitochondria_targeted plastoquinone derivative SkQ1 increases early reproduction of Drosophila melanogaster at the cost of early survival Biochemistry (Moscow), 2010, 75: 265-268.
- Magwire M. M., Yamamoto A., Carbone M. A., Roshina N.V., Symonenko A.V., Pasyukova E. G., Morozova T. V., Mackay T. F. C. Quantitative and molecular genetic analyses of mutations increasing Drosophila life span. PLoS Genet 2010 6(7): e1001037.
- Rybina O. Y., Pasyukova E. G. A naturally occurring polymorphism at Drosophila melanogaster Lim3 locus, a homolog of human LHX3/4, affects Lim3 transcription and fly lifespan. PLoS ONE, 2010, 5(9): e12621.
- Krementsova A. V., Roshina N. V., Tsybul’ko E. A., Rybina O. Y., Symonenko A. V., Pasyukova E. G. Reproducible effects of the mitochondria-targeted plastoquinone derivative SkQ1 on Drosophila melanogaster lifespan under different experimental scenarios. Biogerontology, 2012, v. 13: 595–607.
- Vaiserman A. M., Pasyukova E.G. Epigenetic drugs: a novel anti-aging strategy? Front. Genet., 2012, 3:224.
- Alcedo J., Flatt T., Pasyukova E. G. Neuronal inputs and outputs of aging and longevity. Front. Genet., 2013, 4:71.
- Roshina N. V., Symonenko A. V., Krementsova A. V., Trostnikov M. V., Pasyukova E. G. Embryonic expression of shuttle craft, a Drosophila gene involved in neuron development, is associated with adult lifespan. Aging (Albany NY) 2014, 6:1076-1093.
- Pasyukova E. G., Symonenko A. V., Roshina N. V., Trostnikov M. V., Veselkina E. R., Rybina O. Y. Neuronal genes and developmental neuronal pathways in Drosophila lifespan control. In: Life Extension, Healthy Ageing and Longevity 3, Life Extension: Lessons from Drosophila, Vaiserman A. M. et al. (eds.), Springer International Publishing, Switzerland, 2015, P. 3-37.