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Research Programmes

 

Genome Dynamics

kejnovsky_logo Doc. RNDr. Eduard Kejnovský, CSc.
Research Group Leader

THEMATIC RESEARCH FOCUS

RESEARCH AREAS

  • Genome dynamics in model species and human
  • Microsatellite expansion and transposable element activity in relation to human diseases
  • Introduction of high-throughput analyses into medical research and diagnostics

MAIN OBJECTIVES

  • Study of most dynamic components of genomes – microsatellites and transposable elements – in plants, animal and human.
  • Characterisation of dynamics of transposable elements and their relation to diseases.
  • Induction of transposable elements by stress conditions in model systems.
  • Identification of general mechanisms of microsatellite expansion in genomes.
  • Utilisation of cytogenetic and functional genomic methods and next generation sequencing approaches combined with bioinformatics.

CONTENT OF RESEARCH

Role of genome dynamics in human diseases

The emerging paradigm represents a genome as a very dynamic genetic system generating its own rearrangements. Transposable elements are the key players of genome dynamics. Their activity can be induced by environmental stresses. What is remarkable especially in plants that cannot move is that genome rearrangement can result in a better adaptation. Recent studies show that transposable elements can play a role in cancerogenesis. A new conceptual framework is now emerging that changes the focus from gene mutation to genome aberration, from stepwise progression to stochastic evolution, and from the identification of individual pathways to monitoring of overall instability and dynamics of system. Some cancerogens can represent stressors changing epigenetic landscape of genome and activating transposable elements that in turn reshuffle genome what can lead to cancer development. Therefore, first we will study expression of transposable elements and their activation by various types of environmental stresses in model plant species. Then, we will analyse the activity of transposable elements in human cancer cells and we will correlate the activity of various transposable elements with types of cancer cells and try to use this knowledge for a prognosis of patients. The epigenetic changes will be monitored to elucidate the role of e.g. DNA methylation and RNA interference in transposable element activity.

Microsatellites represent another dynamic component of genomes. Microsatellite expansion in specific genes stands behind many neurodegenerative diseases. Firstly, we will focus on general mechanisms of microsatellite expansion in genomes by analysing next-generation sequencing data from model plant species as well as data from sequenced plants and animal genomes, including human. Later, we will analyse microsatellite expansion both in selected genes and in intergenic regions from patients with various oncological diagnoses.

The introduction of the next generation DNA sequencing, which allows re-sequencing of individual human genomes, will open a new space for medical applications and will give an insight into the causes and development of many human diseases.

Technologies used: massive parallel DNA sequencing (next-generation high-throughput sequencing), gene expression profiling (microarrays, QRT-PCR), bioinformatic analysis.

KEY RESEARCH EQUIPMENT

PLANNED RESEARCH INFRASTRUCTURE

Core Facility

The research group will be one of the principal users of the equipment available within CEITEC Genomics Core Facility.

Technology Units

Genome dynamics

CURRENT RESEARCH INFRASTRUCTURE

At present, the laboratory is equipped with adequate instrumentations for molecular genetics and cytogenetics (PCR cyclers, electrophoretic and gel documentation systems, flowbox, centrifuges, thermostats, hybridisation ovens, crosslinkers, water-baths, deep-freezers, nanodrop, speedvac, etc). The CellCut Plus (MMI, Olympus) machine is a unique tool enabling select, cut and collect cells, subcellular components and specific chromosomes by laser microdissection. The Olympus AX70 research grade microscope for both fluorescence and visible light applications, with highly sensitive monochrome CCD camera (Zeiss AxioCam MRm). Cryomicrotome Leica CM1800 is used for the preparation of tissue sections.

MAIN PROJECTS

  • The role of repetitive DNA sequences in evolution of sex chromosomes in plants (GA204/05/2097), Czech Science Foundation, 2005-2007, Eduard Kejnovský, Institute of Biophysics AS CR.
  • Construction of Silene latifolia BAC library ind its application (GA521/02/0427), Czech Science Foundation, 2002-2004, Eduard Kejnovský, Institute of Biophysics AS CR.
  • Sex chromosomes and dynamics of transposable elements (GAP305/10/0930), Czech Science Foundation, 2010-2014, Eduard Kejnovský, Institute of Biophysics AS CR.

SELECTED PUBLICATIONS

  • KEJNOVSKY, E., LEITCH, I., LEITCH, A. Contrasting evolutionary dynamics between angiosperm and mammalian genomes. Trends in Ecology and Evolution. 2009, 24, p. 572-582.
  • KEJNOVSKY, E., HOBZA, R., KUBAT, Z., VYSKOT, B. The role of repetitive DNA in structure and evolution of sex chromosomes in plants. Heredity. 2009, 102, p. 533-541.
  • MARAIS, G., A., B., NICOLAS, M., BERGERO, R., CHAMBRIER, P., KEJNOVSKY, E., MONEGER, F., HOBZA, R., WIDMER, A., CHARLESWORTH, D. Evidence for degeneration of the Y chromosome in the dioecious plant Silene latifolia. Current Biology. 2008, 18, p. 1-5.
  • KEJNOVSKY, E., HOBZA, R., KUBAT, Z., WIDMER, A., MARAIS, G., A., B., VYSKOT, B. High intrachromosomal similarity of retrotransposon long terminal repeats: Evidence for homogenization by gene conversion on plant sex chromosomes? Gene. 2007, 390, p. 92-97.
  • HOBZA, R., LENGEROVA, M., SVOBODA, J., KUBEKOVA, H., KEJNOVSKY, E., VYSKOT, B. An accumulation of a tandem DNA repeats on the Y chromosome in an early stages of sex chromosome evolution. Chromosoma. 2006, 115, p. 376-382.
 

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