МЕГАГРАНТЫ

Лаборатория системной биологии старения

О лаборатории

Наименование проекта
Белковый синтез в старении и контроле продолжительности жизни

№ договора:

14.W03.31.0012

Сайт лаборатории

Наименование организации
Федеральное государственное бюджетное образовательное учреждение высшего образования "Московский государственный университет имени М.В.Ломоносова"

Область научных исследований
Биология

1: Анализ биосинтеза белка на системном уровне в живом животном.
• Белковый синтез в различных органах мыши будет охарактеризован с помощью оригинальных модификаций новейшего методического подхода – рибосомного профайлинга;
• Будут идентифицированы альтернативные стартовые кодоны и определены изоформы белков в этих органах;
• Аналогичные подходы будут применены к грызунам другого вида - "голым землекопам", которые имеют такие же размеры, но при этом живут в 10 раз дольше мыши.
2: Определение скоростей и особенностей биосинтеза белка в различных органах в видо-, орган-, белок- и диета-специфичном ключе.
• Будут определены скорости синтеза индивидуальных белков в различных органах мыши и "голого землекопа";
• Будет охарактеризована связь регуляции биосинтеза белка с возрастом и диетой (ограничением калорийности питания), а также их влияние на длину рибосомных футпринтов, плотность рибосом на мРНК, метагенные профили, трансляционные паузы и синтез различны изоформ белков;
• Будет охарактеризована регуляция экспрессии генов на уровне мРНК и белков в органах млекопитающих.

Ведущий учёный

Gladyshev 

ФИО: Гладышев Вадим Николаевич

 

Дата рождения 03.01.1966

Гражданство
Россия

Ученые степень и звание
Профессор

Место работы

Больница Бригхэм Гарвардской школы медицины

Область научных интересов

Биология продолжительности жизни; рибосомный профайлинг; окислительно-восстановительная билогия; селеноцистеин-содержащие белки

Достижения и награды

2001 - Junior Faculty Award for Excellence in Research, University of Nebraska-Lincoln
2008 - Outstanding Scientist Award Sigma XI, Nebraska Chapter
2008 - Outstanding Research and Creative Activity (ORCA) Award (top award within University of Nebraska system), University of Nebraska
2009-2013 - Distinguished Professor Ewha Woman’s University, Seoul, Korea
2010 - Eureka award National Institutes of Health
2010 - Gabriel Bertrand Award, Federation of European Societies for Trace Element and Mineral
2011 - AAAS Fellow American Association for the Advancement of Science (AAAS)
2011 - Merit Award, National Institute of Health
2013 - Pioneer Award, National Institute of Health

С 2009 года по н/вр - профессор медицины, Гарвард (США)
С 2009 года по н/вр - директор Центра окислительно-восстановительной медицины (Женская больница Бригхэма, США)
С 2009 года по н/вр - сотрудник Гарвардского института Броада и МТИ, США
С 2009 года по н/вр - сотрудник Гарвардского ракового центра Даны-Фарбер, США
С 2009 года по н/вр - ведущий генетик Отделения медицины Женской больницы Бригхэма, США

Gladyshev VN. (2001) Identity, evolution and functions of selenoproteins and selenoprotein genes. In “Selenium: Its molecular biology and role in human health” (ed., Hatfield DL), Kluwer Academic Publishers, 99-113.

Gladyshev VN, Diamond DL, Hatfield DL. (2001) The 15 kDa selenoprotein (Sep15): functional studies and a role in cancer etiology. In “Selenium: Its molecular biology and role in human health” (ed., Hatfield DL), Kluwer Academic Publishers, 147-155.

Gladyshev VN. (2001) Selenium in biology and human health: controversies and perspectives. In “Selenium: Its molecular biology and role in human health” (ed., Hatfield DL), Kluwer Academic Publishers, 313-317.

Carlson BA, Xu, XM, Shrimali R, Sengupta A, Yoo MH, Irons R, Zhong N, Hatfield DL, Lee BJ, Lobanov AV, Gladyshev VN. (2006) Mammalian and other eukaryotic selenocysteine tRNAs. In “Selenium: Its molecular biology and role in human health” (ed., Hatfield DL, Berry MJ, Gladyshev VN), Springer, 31-40.

Salinas G, Romero H, Xu XM, Carlson BA, Hatfield DL, Gladyshev VN. (2006) Evolution of Sec decoding and the key role of selenophosphate synthetase in the pathway of selenium utilization. In “Selenium: Its molecular biology and role in human health” (ed., Hatfield DL, Berry MJ, Gladyshev VN), Springer, 41-52.

Gladyshev VN. (2006) Selenoproteins and selenoproteomes. In “Selenium: Its molecular biology and role in human health” (ed., Hatfield DL, Berry MJ, Gladyshev VN), Springer, pp. 101-112, 2006.

Kim HY, Gladyshev VN. (2006) Selenium and methionine sulfoxide reduction. In “Selenium: Its molecular biology and role in human health” (ed., Hatfield DL, Berry MJ, Gladyshev VN), Springer, 125-136.

Labunskyy VM, Gladyshev VN, Hatfield DL. (2006) The 15-kDa selenoprotein (Sep15): functional analysis and role in cancer. In “Selenium: Its molecular biology and role in human health” (ed., Hatfield DL, Berry MJ, Gladyshev VN), Springer, 143-150.

Carlson BA, Xu XM, Shrimali R, Sengupta A, Yoo MH, Zhong N, Hatfield DL, Irons R, Davis C, Lee BJ, Novoselov SV, Gladyshev VN. (2006) Mouse models for assessing the role of selenoproteins in health and development. In “Selenium: Its molecular biology and role in human health” (ed., Hatfield DL, Berry MJ, Gladyshev VN), Springer, 337-346.

Результаты исследований


Klepikova A.V., Logacheva M.D., Dmitriev S.E., Penin A.A. (2015) RNA-seq analysis of an apical meristem time series reveals a critical point in Arabidopsis thaliana flower initiation. BMC Genomics, 16: . >>

Dorokhov Y.L., Shindyapina A.V., Sheshukova E.V., Komarova T.V. (2015) METABOLIC METHANOL: MOLECULAR PATHWAYS AND PHYSIOLOGICAL ROLES. Physiol. Rev., 95 (2): 603-644. >>

Andreev D.E., O'Connor P.B.F, Fahey C., Kenny E.M., Terenin I.M., Dmitriev S.E., Cormican P., Morris D.W., Shatsky I.N., Baranov P.V. (2015) Translation of 5' leaders is pervasive in genes resistant to eIF2 repression. eLife, 4: . >>

Putlyaeva L.V., Schwartz A.M., Korneev K.V., Covic M., Uroshlev L.A., Makeev V.Y., Dmitriev S.E., Kuprash D.V. (2014) Upstream Open Reading Frames Regulate Translation of the Long Isoform of SLAMF1 mRNA That Encodes Costimulatory Receptor CD150. Biochem.-Moscow, 79 (12): 1405-1411. >>

Nikonorova I.A., Kornakov N.V., Dmitriev S.E., Vassilenko K.S., Ryazanov A.G. (2014) Identification of a Mg2+-sensitive ORF in the 5 '-leader of TRPM7 magnesium channel mRNA. Nucleic Acids Res., 42 (20): 12779-12788. >>

Spirin P.V., Lebedev T.D., Orlova N.N., Gornostaeva A.S., Prokofjeva M.M., Nikitenko N.A., Dmitriev S.E., Buzdin A.A., Borisov N.M., Aliper A.M., Garazha A.V., Rubtsov P.M., Stocking C., Prassolov V.S. (2014) Silencing AML1-ETO gene expression leads to simultaneous activation of both pro-apoptotic and proliferation signaling. Leukemia, 28 (11): 2222-2228. >>

Shindyapina A.V., Petrunia I.V., Komarova T.V., Sheshukova E.V., Kosorukov V.S., Kiryanov G.I., Dorokhov Y.L. (2014) Dietary Methanol Regulates Human Gene Activity. PLoS One, 9 (7): . >>

Shatsky I.N., Dmitriev S.E., Andreev D.E., Terenin I.M. (2014) Transcriptome-wide studies uncover the diversity of modes of mRNA recruitment to eukaryotic ribosomes. Crit. Rev. Biochem. Mol. Biol., 49 (2): 164-177. >>

Komarova T.V., Petrunia I.V., Shindyapina A.V., Silachev D.N., Sheshukova E.V., Kiryanov G.I., Dorokhov Y.L. (2014) Endogenous Methanol Regulates Mammalian Gene Activity. PLoS One, 9 (2): . >>

Suntsova M., Gogvadze E.V., Salozhin S., Gaifullin N., Eroshkin F., Dmitriev S.E., Martynova N., Kulikov K., Malakhova G., Tukhbatova G., Bolshakov A.P., Ghilarov D., Garazha A., Aliper A., Cantor C.R., Solokhin Y., Roumiantsev S., Balaban P., Zhavoronkov A., Buzdin A. (2013) Human-specific endogenous retroviral insert serves as an enhancer for the schizophrenia-linked gene PRODH. Proc. Natl. Acad. Sci. U. S. A., 110 (48): 19472-19477. >>

Terenin I.M., Andreev D.E., Dmitriev S.E., Shatsky I.N. (2013) A novel mechanism of eukaryotic translation initiation that is neither m(7)G-cap-, nor IRES-dependent. Nucleic Acids Res., 41 (3): 1807-1816. >>

Andreev D.E., Dmitriev S.E., Terenin I.M., Shatsky I.N. (2013) Cap-independent translation initiation of Apaf-1 mRNA based on a scanning mechanism is determined by some features of the secondary structure of its 5 ' untranslated region. Biochem.-Moscow, 78 (2): 157-165. >>

Alexandrova E.A., Olovnikov I.A., Malakhova G.V., Zabolotneva A.A., Suntsova M.V., Dmitriev S.E., Buzdin A.A. (2012) Sense transcripts originated from an internal part of the human retrotransposon LINE-1 5 ' UTR. Gene, 511 (1): 46-53. >>

Shagam L.I., Terenin I.M., Andreev D.E., Dunaevsky J.E., Dmitriev S.E. (2012) In vitro activity of human translation initiation factor eIF4B is not affected by phosphomimetic amino acid substitutions S422D and S422E. Biochimie, 94 (12): 2484-2490. >>

Andreev D.E., Dmitriev S.E., Zinovkin R., Terenin I.M., Shatsky I.N. (2012) The 5 ' untranslated region of Apaf-1 mRNA directs translation under apoptosis conditions via a 5 ' end-dependent scanning mechanism. FEBS Lett., 586 (23): 4139-4143. >>

Andreev D.E., Hirnet J., Terenin I.M., Dmitriev S.E., Niepmann M., Shatsky I.N. (2012) Glycyl-tRNA synthetase specifically binds to the poliovirus IRES to activate translation initiation. Nucleic Acids Res., 40 (12): 5602-5614. >>

Dmitriev S.E., Stolboushkina E.A., Terenin I.M., Andreev D.E., Garber M.B., Shatsky I.N. (2011) Archaeal Translation Initiation Factor aIF2 Can Substitute for Eukaryotic eIF2 in Ribosomal Scanning during Mammalian 48S Complex Formation. Journal of Molecular Biology, 413 (1): 106-114.

Vassilenko K.S., Alekhina O.M., Dmitriev S.E., Shatsky I.N., Spirin A.S. (2011) Unidirectional constant rate motion of the ribosomal scanning particle during eukaryotic translation initiation. Nucleic Acids Research, 39 (13): 5555-5567.

Stepanov A.V., Belogurov A.A., Ponomarenko N.A., Stremovskiy O.A., Kozlov L.V., Bichucher A.M., Dmitriev S.E., Smirnov I.V., Shamborant O.G., Balabashin D.S., Sashchenko L.P., Tonevitsky A.G., Friboulet A., Gabibov A.G., Deyev S.M. (2011) Design of Targeted B Cell Killing Agents. Plos One, 6 (6): -.

Shatsky I.N., Dmitriev S.E., Terenin I.M., Andreev D.E. (2010) Cap- and IRES-Independent Scanning Mechanism of Translation Initiation as an Alternative to the Concept of Cellular IRESs. Molecules and Cells, 30 (4): 285-293.

Dmitriev S.E., Terenin I.M., Andreev D.E., Ivanov P.A., Dunaevsky J.E., Merrick W.C., Shatsky I.N. (2010) GTP-independent tRNA Delivery to the Ribosomal P-site by a Novel Eukaryotic Translation Factor. Journal of Biological Chemistry, 285 (35): 26779-26787.

Andreev D.E., Dmitriev S.E., Terenin I.M., Prassolov V.S., Merrick W.C., Shatsky I.N. (2009) Differential contribution of the m(7)G-cap to the 5' end-dependent translation initiation of mammalian mRNAs. Nucleic Acids Research, 37 (18): 6135-6147.

Dmitriev S.E., Andreev D.E., Adyanova Z.V., Terenin I.M., Shatsky I.N. (2009) Efficient cap-dependent translation of mammalian mRNAs with long and highly structured 5'-untranslated regions in vitro and in vivo. Molecular Biology, 43 (1): 108-113.

Terenin I.M., Dmitriev S.E., Andreev D.E., Shatsky I.N. (2008) Eukaryotic translation initiation machinery can operate in a bacterial-like mode without eIF2. Nature Structural and Molecular Biology, 15 (8): 836-841.

Andreev D.E., Fernandez-miragall O., Ramajo J., Dmitriev S.E., Terenin I.M., Martinez-salas E., Shatsky I.N. (2007) Differential factor requirement to assemble translation initiation complexes at the alternative start codons of foot- and-mouth disease virus RNA. RNA-Publ. RNA Soc., 13 (8): 1366-1374.

Dmitriev S.E., Andreev D.E., Terenin I.M., Olovnikov I.A., Prassolov V.S., Merrick W.C., Shatsky I.N. (2007) Efficient translation initiation directed by the 900-nucleotide-long and GC-rich 5 ' untranslated region of the human retrotransposon LINE-1 mRNA is strictly cap dependent rather than internal ribosome entry site mediated. Molecular and Cellular Biology, 27 (13): 4685-4697.

Olovnikov I.A., Adyanova Z.V., Galimov E.R., Andreev D.E., Terenin I.M., Ivanov D.S., Prassolov V.S., Dmitriev S.E. (2007) Key role of the internal 5'-UTR segment in the transcription activity of the human L1 retrotransposon. Molecular Biology, 41 (3): 453-458.

Andreev D.E., Terenin I.M., Dmitriev S.E., Shatsky I.N. (2006) Similar features in mechanisms of translation initiation of mRNAS in eukaryotic and prokaryotic systems. Molecular Biology, 40 (4): 694-702.

Andreev D.E., Terenin I.M., Dunaevsky Y.E., Dmitriev S.E., Shatsky I.N. (2006) A leaderless mRNA can bind to mammalian 80S ribosomes and direct polypeptide synthesis in the absence of translation initiation factors. Molecular and Cellular Biology, 26 (8): 3164-3169.

Dmitriev S.E., Bykova N.V., Andreev D.E., Terenin I.M. (2006) Adequate system for investigation of the human retrotransposon L1 mRNA translation initiation in vitro. Molecular Biology, 40 (1): 25-30.

Terenin I.M., Dmitriev S.E., Andreev D.E., Royall E., Belsham G.J., Roberts L.O., Shatsky I.N. (2005) A cross-kingdom internal ribosome entry site reveals a simplified mode of internal ribosome entry. Molecular and Cellular Biology, 25 (17): 7879-7888.

Varfolomeyev S., Efremenko E., Beletskaya I., Bertini I., Blackburn G.M., Bogdanov A., Cunin R., Eichler J., Galaev I., Gladyshev V., o'hagan D., Haertle T., Jarv J., Karyakin A., Kurochkin I., Mikolajczyk M., Poroikov V., Sakharov I., Spener F., Voyer N., Wild J. (2005) Postgenomic chemistry (IUPAC Technical Report). Pure and Applied Chemistry, 77 (9): 1641-1654.

Pisarev A.V., Dmitriev S.E., Shatsky I.N. (2004) Mutual effects of translation initiation factors in binding to the IRES of the encephalomyocarditis virus RNA. Molecular Biology, 38 (2): 261-265.

Dmitriev S.E., Terenin I.M., Dunaevsky Y.E., Merrick W.C., Shatsky I.N. (2003) Assembly of 48S translation initiation complexes from purified components with mRNAs that have some base pairing within their 5 ' untranslated regions. Molecular and Cellular Biology, 23 (24): 8925-8933.

Rubtsova M.P., Sizova D.V., Dmitriev S.E., Ivanov D.S., Prassolov V.S., Shatsky I.N. (2003) Distinctive properties of the 5 '-untranslated region of human Hsp70 mRNA. Journal of Biological Chemistry, 278 (25): 22350-22356.

Dmitriev S.E., Terenin I.M., Rubtsova M.P., Shatsky I.N. (2003) Minor secondary-structure variation in the 5 '-untranslated region of the beta-globin mRNA changes the concentration requirements for eIF2. Molecular Biology, 37 (3): 421-428.

Dmitriev S.E., Pisarev A.V., Rubtsova M.P., Dunaevsky Y.E., Shatsky I.N. (2003) Conversion of 48S translation preinitiation complexes into 80S initiation complexes as revealed by toeprinting. FEBS Letters, 533 (1): 99-104.

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