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Functional Genomics

Research Focus

Functional Genomics_credit R. Sedláček

The genomes of humans, mice and many other species have been completely sequenced; nevertheless the knowledge of genome sequences as such does not shed light on questions concerning the functions of these sequences. Among the unanswered questions are those regarding the functions of most of the genes that encode proteins; the number of these genes is estimated to be 20 000. In order to describe biological functions of a gene, an informative modification (mutation, for instance a conditional deletion) must be inserted into the genes.

In order to annotate the function of human genes, functional (pheno)genomics needs to be combined with comparative genomics – the function of the human genome should be inferred from the function of an orthologous genetic product, e.g. from the mouse .

In recent years, mouse and rat models have been considered excellent models in the search for functions of genes within complex organisms as most of their physiological functions are very similar to those of humans and, also, their genetic differences are minimal (in comparison to other non-mammalian models). Although characterization of the function of a particular gene product (i.g. protein) in vitro delivers important information about molecular mechanisms, the verification of their real functions cannot be done without an intensive research at the level of complex organisms and their distinct physiological systems.

Functional genomics research program is based on previous work of a few research groups that have built up a substantial expertise and have already attained considerable scientific results in this field.

Institutional research program guarantor:

Goals

výstupy_FG programme

Supported from a robust and standardized phenotyping platform offering a functional screening of almost all physiologic body systems, the groups of this program aim to identify and characterize genes representing new potential targets to treat various human diseases. Main effort focuses on metabolic syndrome and physiologic functions interrelated with this complex human disease. Identified genes and genetic determinants will be then scrutinized for their potential to employ them as therapeutic targets. Beside the liver and metabolic disorders, research projects will focus also on visual and auditory systems whose correct functions is of enormous importance for human’s life quality and well-being. Genes important for the physiologic systems will be identified, examined, and prove whether they could serve as a diagnostic markers or therapeutic targets. Once the therapeutic potential is proved researches will together with drug developing groups or companies study the drug efficacy employing the know-how, capacity, and experimental models of the CCP.

Head of Program

Assoc. Prof. Radislav Sedláček, Ph.D.

04_Radislav Sedlacek_04
  • Assoc. Prof. Radislav Sedláček, Ph.D.

  • Member of the Board, Head of Program Functional Genomics, Head of Czech Centre for Phenogenomics
  • Head of Group - Phenogenomics: Systematic phenotypic analysis of mice and rat mutant models for the annotation of gene function
  • +420 325 873 243
  • curriculum vitae

Profile

His scientific career has been devoted to understanding the function of
metalloproteinases, especially their role in vivo using mouse models.

Radek Sedláček was recruited to IMG to establish transgenic technology and infrastructure for generation, archiving and distribution of mouse models;

- he supports a number of scientific groups in the Czech Republic and European countries with his expertise in the field of generation of transgenic mouse models, he  proposed, designed, and is managing the Czech Centre for Phenogenomics (CCP) that is integral part of the Programme on Functional Genomics;

- besides being a member of the Board of Directors of EMMA and INFRAFRONTIER, he also represents the Czech Republic in the Thematic Working Group on Biological and Medical sciences (BMS) under ESFRI (European Strategy Forum on Research Infrastructures) and coordinates BMS infrastructures in the Czech Republic. R. Sedláček holds also broad interaction with national and international scientific partners in the field of mouse disease models and functional genomics. These expertise and interactions link together the groups of the research programme and create a cooperation base for external partners.

Most Significant Recent Publications

Flemr M, Malik R, Franke V, Nejepinska J, Sedlacek R, Vlahovicek K, Svoboda P: A retrotransposon-driven dicer isoform directs endogenous small interfering RNA production in mouse oocytes. Cell. 2013 Nov 7;155(4):807-16. doi: 10.1016/j.cell.2013.10.001.

Buryova H, Chalupsky K, Zbodakova O, Kanchev I, Jirouskova M, Gregor M, Sedlacek R.: Liver protective effect of ursodeoxycholic acid includes regulation of ADAM17 activity. BMC Gastroenterol. 2013 Oct 30;13(1):155. [Epub ahead of print]

Klimova L, Lachova J, Machon O, Sedlacek R, Kozmik Z. : Generation of mRx-Cre transgenic mouse line for efficient conditional gene deletion in early retinal progenitors. PLoS One. 2013 May 7;8(5):e63029. doi: 10.1371/journal.pone.0063029. Print 2013.

Fafilek B., Krausova M, Vojtechova M, Pospichalova V, Tumova L, Sloncova E., Huranova M., Chmelikova  J., Hlavata A., Svec J., Sedlacek R., Luksan O., Oliverius M, Voska L., Jirsa M., Paces J., Kolar M., Krivjanska M., Klimesova K., Tlaskalova-Hogenova H. and Korinek V. 2012. Troy, a Tumor Necrosis Receptor Family Member 19, Interacts with Lgr5 to Inhibit Wnt Signaling in Intestinal Stem Cells. Gastroenterology. 2013 Feb;144(2):381-91

Jirouskova M., Zbodakova O., Gregor M., ChalupskyK, Sarnova L., Hajduch M, Ehrmann J., Jirkovska M., and Sedlacek R. 2012. Hepatoprotective effect of MMP-19 deficiency in a mouse model of chronic liver fibrosis. PLOS One ( in press).

Reiss K., Meyer-Hoffert U., Fischer J., Sperrhacke M., Wu Z., Dimitrieva O., Krenek P., Suchanova, S., Buryova H., Brauer R., and Sedlacek R. 2011. Expression and regulation of murine SPINK12, a potential orthologue of human LEKTI2. Exp. Dermatology 20(11):905-10.

Kasparek Petr., Krenek P., Buryova H., Suchanova S., Beck I.M., and Sedlacek R. 2011. Transgenic mouse model expressing tdTomato under involucrin promoter as a tool for analysis of epidermal differentiation and wound healing. Transgenic Research (in press)

Group Profile (Home Institution)

Publications

2013



  • Youngson N.A., Epp T., Roberts A.R., Daxinger L., Ashe A., Huang E., Lester K.L., Harten S., Kay G.F., Cox T., Matthews J.M., Chong S. and Whitelaw E.: No evidence for cumulative effects in a Dnmt3b hypomorph across multiple generations. 2013. Mammalian Genome.

  • Bhattacharyya T, Gregorova S, Mihola O, Anger M, Sebestova J, Denny P, Simecek P, Forejt J.: Mechanistic basis of infertility of mouse intersubspecific hybrids. Proc Natl Acad Sci U S A. 2013 Jan 17.


 

2012



  • Fafilek B, Krausova M, Vojtechova M, Pospichalova V, Tumova L, Sloncova E, Huranova M, Stancikova J, Hlavata A, Svec J,Sedlacek R, Luksan O, Oliverius M, Voska L, Jirsa M, Paces J, Kolar M, Krivjanska M, Klimesova K, Tlaskalova-Hogenova H,Korinek V: Troy, a Tumor Necrosis Factor Receptor Family Member, Interacts With Lgr5 to Inhibit Wnt Signaling in Intestinal Stem Cells. Gastroenterology 2012. [pubmed] [doi]

  • Jirouskova M, Zbodakova O, Gregor M, Chalupsky K, Sarnova L, Hajduch M, Ehrmann J, Jirkovska M, Sedlacek R: Hepatoprotective Effect of MMP-19 Deficiency in a Mouse Model of Chronic Liver Fibrosis. PLoS One 2012 7(10): e46271. [pubmed] [doi]

  • Kasparek P, Krenek P, Buryova H, Suchanova S, Beck IM, Sedlacek R: Transgenic mouse model expressing tdTomato under involucrin promoter as a tool for analysis of epidermal differentiation and wound healing. Transgenic Res 201221(3): 683-9. [pubmed] [doi]

  • Kollmus H, Post R, Brielmeier M, Fernández J, Fuchs H, McKerlie C, Montoliu L, Otaegui PJ, Rebelo M, Riedesel H, Ruberte J,Sedlacek R, de Angelis MH, Schughart K: Structural and functional concepts in current mouse phenotyping and archiving facilities. J Am Assoc Lab Anim Sci 2012 51(4): 418-35. [pubmed]

  • Laššuthová P, Gregor M, Sarnová L, Machalová E, Sedláček R, Seeman P: Clinical, In Silico, and Experimental Evidence for Pathogenicity of Two Novel Splice Site Mutations in the SH3TC2 Gene. J Neurogenet 2012 26(3-4): 413-20. [pubmed] [doi]

Contacts

+420 325 873 246
libor.danek@img.cas.cz