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LABORATORY OF BIOMEDICAL RESEARCHE



Head of Laboratory:

    Shishkin Sergey Sergeevich,
    professor, Dr.Biol.Sci., member of Human Genome Organization,
    the author more than 300 publications in Russian and foreign periodicals, and also three monographies and several inventions.
    tel.:  +7(495)-952-58-86
    e-mail: shishkin AT inbi.ras.ru

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General data:
    The laboratory of biomedical research is formed in 2002 after transition in A.N. Bach Institute of Biochemistry of the Russian Academy of Science the basic personnel of laboratory of the biochemical genetics working more 20 years in the Research Centre of Medical Genetics of Russian Academy of Medical Science. Now in laboratory of biomedical RESEARCHE are working two doctors of the sciences and three Ph. D. scientists; three post-graduates are preparing the dissertational investigations; on a regular basis there pass training several students of medical faculty RUDN, and also students of other Institutions of biological and medical specialities.
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Areas of interests and priorities:
    The systematic investigation of contractile, cytoskeletal and some other human proteins by use the proteomics strategy with aims the study of polymorphic proteins and revealing of new human proteins, and also on search of proteins - markers for various pathological processes (dystrophies and dysplasies, oncological diseases, etc.) with the subsequent development of diagnosis tools.
    The studying of nucleotides polymorphisms (including single nucleotide polymorphism [SNP]) in human genes, expressed in tissues of the locomotor apparatus (in particular in muscular tissues), development of DNA-diagnostics methods for the hereditary diseases shown by infringements of work of the locomotor apparatus and for application of these methods in medical practice.
    The studying of biochemical mechanisms of formation and functioning of human muscular tissues in norm and at a hereditary pathology, including researches of molecular effects from action various growth factors on muscular cells. Creation of a cell-culture collections (in particular, human myoblasts) from healthy donors and from patients with various forms of hereditary diseases for use of these cellular models at studying biochemical mechanisms of action various growth factors, and also a cellular differentiation.
    The main directions of the present activity
    Proteomic researches of proteins in human muscular tissues and in several cell cultures are carrying out with purpose of the study a role of different actin-binding proteins and some polymorphic proteins in maintenance of high muscular serviceability, and also during a differentiation and at different forms of a muscular pathology. There are proteomic researches of proteins in human prostate tissues and in cultivated cancer cells for revealing potential molecular markers of prostate cancer.
    It is carry out the study of nucleotide polymorphisms (SNP's, etc.) in several human genes for the revealing of associations with ability to high muscular serviceability (in particular, in genes ACTN3, TTN, GHR, IL15RA, MSTN, GH, IGF1, COMP), and also for diagnostics of myodystrophies (by use the study of DMD, CANP3 genes) and cardiomyophaties with revealing associations of the some SNP's with a sudden death syndrome (by use the study of MYH7, HERG, TTN, TPM1, MYL1 genes).
    It is develop and use of cellular models for investigation of biological activity of recombinant growth factors and biochemical mechanisms of their action.
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Main achievements:
    Using the results of proteomic researches of muscular proteins (which were carried out on bioptats and autoptats specimens of human tissues, and also on human myoblast cultures) it was development of computer protein databank GEP-HM in which the quantity of the identified proteins up to 120 is increased. Polymorphisms at a lot of the muscular proteins are revealed and characterized: proteins, directly participating in contractile functions (some myosin heavy chains, two isoforms of troponin Ò1, two isoforms of troponin Ò3, isoform of troponin I, some products of tropomyosin and actin genes, etc.); some cytosol enzymes (isoforms H and L of β-enolase - protein products of gene ENO3, isoforms with amino acid substitution 41E?A at δ3,5-δ2,4-dienoyl-coezyme-A isomerase - protein products of gene ECH1, etc.); some cytoskeletal proteins (in particular, proteins of Z band in which contain alternatively spliced PDZ motives). One of the analyzed proteins has been identified as a product corresponding to hypothetical gene PRO 1496 which is found out in human genome.
    At comparative proteomic analysis of specimens of human prostate tissues with benign prostatic hyperplasia and with malignant tumors a number of quantitative and qualitative changes of proteins has been revealed. In particular, it was possible on the some samples to identify protein AGR2 which was present at a prostate cancer and was absent at benign prostatic hyperplasia. This result is corresponding well to some publications of 2005 and gives the basis to consider protein AGR2 as a potential new marker of a prostate cancer.
    Some representative DNA-collections of sportsmen (with the top skills and beginning) are collected; at their study (using the restriction analysis and the method of allele discrimination on a basis of real time polymerase chain reaction) the associations of some SNP's in genes ACTN3, GHR, IL15RA and MSTN with ability to high muscular serviceability are found out in elite swimmers and it is revealed that these associations can be used for the specialization of young sportsmen. During medical consultation of several patients with Limb Girdle Muscular Dystrophy (Erb-Rot disease) and subsequent DNA-analysis (PCR, SSCP-analysis and sequencing) it is identified new dinucleotide deletion (AC) in exon 21 of CANP3 gene which it is registered in the international database "Nucleotide" NCBI - AY823489, gi56126469.
    By use the modernized special cellular biotest-system, biological effects of some growth factors on human myoblast and fibroblast cultures are investigated. Biological activity several recombinant growth factors (myostatin, mechano-growth factor [MGF] and insulin-like growth factor-1) in a wide range of concentration (from 0,5 up to 64 íã/ml) is determined by different ways. It is shown, that the given modelling system allows to carry out testing of proliferative activity, and the investigated factors possess corresponding activity.
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Partners:
    Institute of Biomedical Problems, RAS – O.L. Vinogradova, professor, head of department and I.M.Larina, professor, head of department; Orekhovich Research Institute of Biomedical Chemistry, RAMS - A.B. Lisizha, Ph. D., deputy director; Sechenov Moscow Medical Academy - P.Z.Khasigov, D.Med. Sci., head of department and A.A. Ivanov, professor, deputy director; Institute of Urology, Ministry of Public Health of RF - N.K. Dzeranov, professor, head of department; Russian University of People's Friendship - N.N. Chernov, professor, head of department of biochemistry; Children’s Psycho-Neurological Hospital of Moscow Region - N.I. Shakhovskaya, Ph. D. deputy director; Voronezh State University – T.N. Popova, professor, head of department and some other.
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The most successful projects:
    Scientists and other employees of laboratory took part in successful realization of the following projects: State program "Medical and molecular technologies for the increasing of human muscular serviceability in condition of intense physical loadings”. 2003-2004 - coauthors under contracts (Head of the Program – member of Russian Academy of Science A.I.Grigorjev); Federal program “Handicap children”. 2002. Agreement N902-D “The development of computer database about families with patients suffering hereditary mandelian diseases, that have neuro-psychiatric symptoms” (Head of the investigation – professor S.S. Shishkin); Grant of RFFI N03-04-49376 “The study of the organo- and tissue specificity of sarcolemmal and cytoskeletal muscular proteins in ontogenesis”, 2003-2005. (Head of the investigation - Dr. Biol. Sci. L.I. Kovalyov); Grant of RFFI N02-04-48879 “The study of differentiation of human muscle cells in culture; genetic control and effects of several factors”, 2002-2003. (Head of the investigation – professor S.S. Shishkin).

The current projects
    In the present time the employees of laboratory take part in the following projects: The complex project of Ministry of Science, RF - GS-CP N6/002 “Medico-biological technologies of the increasing of human muscular serviceability in condition of intense physical loadings”. (2005-2006); The Program of Presidium of Russian Academy of Science “Fundamental sciences for Medicine” - Project “The study of polymorphisms of actin-binding proteins at prostate cancer and their roles in maintenance high abilty of cancer cells to invasion” (2006-2008) and Project “The study of polymorphisms in the genes determining human mental properties; Moscow committee of Science and technologies - Project “The investigation of molecular alterations at a prostate cancer for development of effective methods of diagnostics” (2006-2007).
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Last review: 17 June, 2006
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