A. Personal Data NAME Elena G. Pasyukova INSTITUTIONAL AFFILIATION Institute of Molecular Genetics of Russian Academy of Sciences (IMG RAS) POSITION TITLE Head, Laboratory of Genome Variation EDUCATION/TRAINING Moscow State University IMG RAS IMG RAS IMG RAS B. M.Sc. (Genetics) Ph.D. (Genetics) D.Sci. (Genetics) Professor (Genetics) 06/1977 11/1986 06/1999 10/2013 Personal Statement Since 1997, the main goal of my 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 my 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 the four main lines. The first line of my 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. The second line of my 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. The third line of my 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. The fourth line of my 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 and neuron function. We demonstrated that the level of expression of the gene encoding GSK3-β affects synaptic activity, behavior and lifespan. In addition, substantial part of my 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. C. Positions and Honors Positions and Employment 1977 – 1979 Junior Researcher, Department of Genetics, Biological College of Moscow State University, Moscow, Russia. 1980 – present Junior Researcher, Researcher, Senior Researcher, Leading Researcher, and (currently) Head of the Laboratory, Institute of Molecular Genetics of RAS, Moscow, Russia. *** 1991,1993 Visiting Scientist, Laboratory of Biology, Genetics and Biometry, University Lyon 1, France. 1994 Academic Visitor, Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, U.K. 1995,1997,1999, Visiting Scientist, Department of Genetics, North Carolina State University, USA. 2002, 2005 2006 – present Invited Lecturer, Department of Genetics, Biological College of Moscow State University, Moscow, Russia. 2011 – present Editorial Board, International Journal of Genomics. 2011 – present Associate Editor, Frontiers in Genetics of Aging. Honors and Awards 2002 D. Russian Federation State Award in Science and Technology. Selected Peer-reviewed Publications (14 out of 72, total citation 1840, h-index 22) 1. Nuzhdin, S. V., Pasyukova, E. G., Dilda, C. L., Zeng, Z.-B., and Mackay, T. F. C. 1997. Sex-specific quantitative trait loci affecting longevity in Drosophiala melanogaster. Proc. Natl. Acad. Sci. USA, 94:9734-9739. 2. Vieira, C., Pasyukova, E. G., Zeng, Z.-B., Hackett, J. B., Lyman, R. F., and Mackay, T. F. C. 2000. Genotype-environment interaction for quantitative trait loci affecting lifespan in Drosophila melanogaster. Genetics, 154:213-227. 3. Pasyukova, E. G., Vieira, C., and Mackay, T. F. C. 2000. Deficiency mapping of quantitative trait loci affecting longevity in Drosophila melanogaster. Genetics, 156:1129-1146. 4. De Luca, M., Roshina, N. V., Geiger-Thornsberry, G. L., Lyman, R. F., Pasyukova, E. G., and Mackay T. F. C. 2003. Dopa decarboxylase (Ddc) affects variation in Drosophila longevity. Nat. Genet., 34:429-33. 5. Pasyukova E. G., Roshina N. V., and Mackay T. F. C. 2004. Shuttle craft: a candidate quantitative trait gene for Drosophila lifespan. Aging Cell, 3:297-307. 6. Mackay T.F.C., Roshina N.V., Leips J.W., Pasyukova E.G. 2005. Complex genetic architecture of Drosophila longevity. Handbook on the Biology of Ageing, Ed. Masoro E., Austad S., 6:181-216. 7. 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. 2009. An attempt to prevent senescence: a mitochondrial approach. BBA Bioenergetics, 1787:437-461. 8. Magwire M. M., Yamamoto A., Carbone M. A., Roshina N.V., Symonenko A.V., Pasyukova E. G., Morozova T. V., Mackay T. F. C. 2010. Quantitative and molecular genetic analyses of mutations increasing Drosophila life span. PLoS Genet., 6(7): e1001037. 9. Rybina O. Y., Pasyukova E. G. 2010. A naturally occurring polymorphism at Drosophila melanogaster Lim3 locus, a homolog of human LHX3/4, affects Lim3 transcription and fly lifespan. PLoS ONE, 5(9): e12621. 10. Vaiserman A. M., Pasyukova E.G. Epigenetic drugs: a novel anti-aging strategy? 2012. Front. Genet., 3:#224. 11. Krementsova A. V. , Roshina N. V., Tsybul’ko E. A., Rybina O. Y., Symonenko A. V., Pasyukova E. G. 2012. Reproducible effects of the mitochondria-targeted plastoquinone derivative SkQ1 on Drosophila melanogaster lifespan under different experimental scenarios. Biogerontology, 13:595–607. 12. Alcedo J., Flatt T., Pasyukova E. G. 2013. Neuronal inputs and outputs of aging and longevity. Front. Genet., 4:#71. 13. Roshina N. V., Symonenko A. V., Krementsova A. V., Trostnikov M. V., Pasyukova E. G. 2014. Embryonic expression of shuttle craft, a Drosophila gene involved in neuron development, is associated with adult lifespan. Aging (Albany NY) 6:1076-1093. 14. Pasyukova E. G., Symonenko A. V., Roshina N. V., Trostnikov M. V., Veselkina E. R., Rybina O. Y. 2015. 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, P. 3-37. E. Current Research Support 1. Russian Foundation for Basic Research grant # 15-04-05797, 2015-2017. PI Pasyukova E. G. “Analysis of the role of differential expression of the stc and esg genes encoding transcription factors involved in the control of development of the nervous system in determination of lifespan, the nervous system functioning and transcription”. 2. Russian Foundation for Basic Research grant # 15-54-46009, 2015-2016. PI Pasyukova E. G. “Latitudinal, seasonal, and year-to-year changes in genome, transcriptome, and life history traits variation in Drosophila melanogaster populations”. 3. Russian Academy of Sciences program “Biodiversity” grant, 2009- 2015. PI Pasyukova E. G. “Molecular variation of genes involved in neuron development and longevity control in Drosophila natural populations”.