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Research topics

Genomics, evolutionary biology, expression profiling in oncology

Genomics and bioinformatics belong to the most vigorously developing disciplines of contemporary life sciences. The Laboratory of Genomics and Bioinformatics was amongst the first laboratories to complete a genome project. It was in the mid eighties when the complete nucleotide sequence of the bacteriophage PZA DNA was determined. Since then the laboratory has been developing new approaches and strategies to the large-scale DNA sequencing and was involved in several international genome projects such bovine herpesvirus genome project, Saccharomyces cerevisiae genome project and Rhodobacter capsulatus genome project. Information generated in these projects was used in evolutionary studies and recently also in biotechnological applications. In collaboration with other groups of the Institute individual members of the Laboratory became involved in characterization of several developmental genes and in studies on transcriptional profiles of expression of several mouse genes. The tools of bioinformatics were developed in order to analyze nucleotide sequences generated in these projects as well as those available in the international databases. In collaboration with the laboratory of Zbyněk Kozmík we begin to characterize genes expressed in the rhopalium, a special multifunctional organ of the cubozoan jellyfish Tripedalia cystophora. The genome project of Rhodobacter capsulatus has been completed. Several genes with possible biotechnology applications are now being characterized. In previous years, a special attention was given to human genome analysis, namely to the isochore structures of individual human chromosomes. In addition, distribution of Alu and LINE repetitive sequences was characterized. HERVd, the database of human endogenous retroviruses was assembled. This database is now available at herv.img.cas.cz. It is being used for detailed characterization of HERVs, their integration, stability, and distribution.

Current grant support

Ministry of Education, Youth and Sports of the Czech Republic (Center for Applied Genomics, grant No.: 1M6837805002)
Ministry of Education, Youth and Sports of the Czech Republic (NPV II, grant No.: 1M0520)

Most important recent papers

(2004-present; names of the lab members underlined)

Drabkova, L., Kirschner, J., Vlcek, C., Paces, V.: TrnL-trnF intergenic spacer and trnL intron define clades within Luzula and Juncus (Juncaceae). J. Mol. Evol. 59: 1-10, 2004. (PubMed)

Paces, J., Pavlicek, A., Zika, R., Kapitonov, V. V., Jurka, J., Paces, V.: HERVd: the Human Endogenous Retrovirus Database: update. Nucleic Acids Res. 32: 50, 2004. (PubMed)

Urbanek, P., Paces, J., Paces, V.: An approach towards experimental cDNA sequence determination of predicted genes: An example from Arabidopsis U3-55k homologues. Gene 358: 67-72, 2005. (PubMed)

Divina, P., Vlcek, C., Strnad, P., Paces, V., Forejt, J.: Global transcriptome analysis of the C57BL/6J mouse testis by SAGE: evidence for nonrandom gene order. BMC Genomics 6: 1-17, 2005. (PubMed)

Belshaw, R., Katzourakis, A., Paces, J., Burt, A., Tristem, M.: High copy number in human endogenous retrovirus families is associated with copying mechanisms in addition to reinfection. Mol. Biol. Evol. 22: 814-817, 2005. (PubMed)

Pavlicek, A., Gentles, A.J., Paces, J., Paces, V., Jurka, J.: Retroposition of processed pseudogenes: the impact of RNA stability and translational control. Trends Genet. 22: 69-73, 2006. (PubMed)

Bukovska, G., Klucar, L., Vlcek, C., Adamovic, J., Turna, J., Timko, J.: Complete nucleotide sequence and genome analysis of bacteriophage BFK20--a lytic phage of the industrial producer Brevibacterium flavum. Virology 348: 57-71, 2006. (PubMed)

Farkasovska, J., Klucar, L., Vlcek, C., Kokavec, J., Godany, A.: Complete genome sequence and analysis of the Streptomyces aureofaciens phage mu1/6. Folia Microbiol (Praha) 52: 347-58, 2007. (PubMed)

Fujimura, N., Vacik, T., Machon, O., Vlcek, C., Scalabrin, S., Speth, M., Diep, D., Krauss, S., Kozmik, Z.: Wnt-mediated down-regulation of Sp1 target genes by a transcriptional repressor Sp5. J. Biol. Chem. 282: 1225-37, 2007. (PubMed)

Hoyerova, K., Perry, L., Hand, P., Lankova, M., Kocabek, T., May, S., Kottova, J., Paces, J., Napier, R., Zazimalova, E.: Functional characterization of PaLAX1, a putative auxin permease, in heterologous plant systems. Plant Physiol. 146: 1128-41, 2008. (PubMed)

Kozmik, Z., Swamynathan, S.K., Ruzickova, J., Jonasova, K., Paces, V., Vlcek, C., Piatigorsky, J.: Cubozoan crystallins: evidence for convergent evolution of pax regulatory sequences. Evol. Dev. 10: 52-61, 2008. (PubMed)

Trachtulec, Z., Vlcek, C., Mihola, O., Gregorova, S., Fotopulosova, V., Forejt, J.: Fine haplotype structure of a chromosome 17 region in the laboratory and wild mouse. Genetics 178: 1777-84, 2008. (PubMed)

Jencova, V., Strnad, H., Chodora, Z., Ulbrich, P., Vlcek, C., Hickey, W.J., Paces, V.: Nucleotide sequence, organization and characterization of the (halo)aromatic acid catabolic plasmid pA81 from Achromobacter xylosoxidans A8. Res. Microbiol. 159: 118-27, 2008. (PubMed)

Kozmik, Z., Ruzickova, J., Jonasova, K., Matsumoto, Y., Vopalensky, P., Kozmikova, I., Strnad, H., Kawamura, S., Piatigorsky, J., Paces, V., Vlcek, C.: Assembly of the cnidarian camera-type eye from vertebrate-like components. Proc. Natl. Acad. Sci. USA 105: 8989-93, 2008. (PubMed)

Kolar, M., Lassig, M., Berg, J.: From protein interactions to functional annotation: graph alignment in Herpes. BMC Syst. Biol 2: 90, 2008. (PubMed)

Mihola, O., Trachtulec, Z., Vlcek, C., Schimenti, J.C., Forejt, J.: A mouse speciation gene encodes a meiotic histone H3 methyltransferase. Science 323: 373-5, 2009. (PubMed)

Future plans

Since 2006, the "Oncogene" is a project directed towards identification of specific markers in cancer tissue with potential applications in medical diagnosis. We are going to use Affymetrix and Illumina microarray chip analyses for detection of appropriate gene sets.

The Center for Applied Genomics was established in 2005 with a five-year grant from the Ministry of Education, Youth and Sports. The aim of the project is to establish in the Czech Republic a base for the complex study of genomes, and thereby create conditions for utilizing genomics in basic as well as applied biomedical research, in pharmaceutical applications and in biotechnology. To achieve this several leading laboratories have combined their efforts and experience with a variety of relevant methods. The project "Center for Applied Genomics" has its own web-page.

To understand the evolution of higher metazoan genomes and the developmental processes that they regulate, it is necessary to make comparisons with an appropriate outgroup. The Cnidaria, a group of lower Metazoa, are the natural outgroup for comparative genomics and developmental studies. An extra germ layer and a second axis of body symmetry are the features that distinguish higher Metazoa from lower animals such as cnidarians. The availability of the model animal genomic sequences will allow inferences to be made about the gene complement of the common bilaterian ancestor. Cnidarian genomes are potentially a key to understanding many aspects of animal evolution. We plan to trial our genomic potential and begin characterize genomes and genes of some cnidarian species, among them Aitplasia pulchella, Cracpedacusta sowerbyi and Tripedalia cystophora.