Department of Cell Biology and Radiobiology (DCBR)

Head: Falk Martin, RNDr., Ph.D. (falk@ibp.cz; +420-728084060)

Research profile DCBR

In the Department of Cell Biology & Radiobiology, we investigate a broad scale of questions associated with structure and function of chromatin and DNA–molecular complexes in humans and plants. We are mostly interested in the principles of chromatin organization in nuclei of eukaryotic cells and relationships between chromatin architecture and function upon physiological and pathological conditions, structure and evolution of telomeres, and functions of non-coding DNA and RNA. Radiobiological and pharmaceutical research focuses on the complex response of cells to irradiation with various types of ionizing radiation, especially DNA damage and repair in the context of chromatin architecture. In connection with the development of radiotherapy and space research, we also study the possibilities of influencing DNA damage and repair using radioprotectors and radiosensitizers. The Department is organized in four research groups:

 

Research Keywords

Chromatin and DNA–molecular complexes in vital and pathological processes in humans and plants

  • Structure & function of chromatin and DNA–molecular complexes in regulation of physiological and pathological processes in the cell nucleus with an emphasis on carcinogenesis
  • DNA damage, repair and misrepair in the context of chromatin architecture
  • Epigenetics
  • Telomere biology and evolution
  • Non-coding DNA and RNA
  • DNA damage and Repair, Radiobiology, Radiation BiophysicsDNA damage and repair at the micro- and nanoscale
  • Chromatin as a network in the systemic response to DNA damage
  • Relationships between DNA damage repair, type of damaging agent (see below), chromatin architecture, cell type, etc.
  • Chromatin architecture in regulation of DNA repair at individual DSB sites
  • Mechanisms of DNA double strand break (DSB) induction, repair, and misrepair

Radiotherapy, Space Research, CBRN, Radiation Protection and Pharmacology

  • DNA damage and repair upon exposure to different types of ionizing radiation, CBRN or anti-cancer drugs, relationships to chromatin architecture
  • Hadron (ion-beam) cancer therapy
  • Radiosensitizers, radioprotectives and pharmacology for radiotherapy, space exploration, and civil protection
  • Nanomedicine – metal nanoparticles as tumor cell-specific radio-enhancers and theranostic agents
  • Biomarkers and software for biodosimetry and radiobiological research
  • Hypoxia
  • Immuno-Radio Therapy
  • Cryo-Radio Therapy

 

Research Methods:

cell culture (in hypoxia), immunofluorescence confocal microscopy, superresolution microscopy, Single Molecule Localization Microscopy (SMLM) and COMBO-FISH – in cooperation (KIP, Heidelberg University), live cell microscopy, 3D fluorescent in situ hybridization (FISH), immuno-FISH, immuno-cytochemistry, Western blotting, PCR, qRT-PCR, functional genomics and transcriptomics, cell transfection, gene silencing,  real-time cell proliferation and migration, image analysis, micro-induction of DNA double-strand breaks at a subnuclear level, g-irradiation (proton and ion-beam irradiation at cooperating institutes)

 

RESEARCH GROUPS

1. Laboratory of Chromatin Function, Damage, and Repair (Martin Falk, falk@ibp.cz) investigates the roles of chromatin architecture in vital and pathological cell processes, especially carcinogenesis and processes provoked by exposure to ionizing radiation. Of research interest are the effects of different kinds of ionizing radiations (g, accelerated protons and heavy ions) and CBRN on normal and tumor cells, especially the character of DNA damage and mechanisms of DNA repair. The research group tries to reveal what roles play the chromatin structure, epigenetic modifications, and nuclear architecture in the cell response to irradiation, genome instability and spontaneous damage, and carcinogenesis. Important questions to address include a) the function of the chromatin network in the systemic response to radiation (DNA damage) of the cell as a whole and b) the regulation of DNA repair at individual double-strand break (DSB) sites. The researchers extensively explore how to make the best use of current radiotherapy and how to improve it further; nowadays, they mostly study the radiosensitizing effect of metal nanoparticles (nanomedicine).

2. Laboratory of Experimental Pharmacology and Radiobiology (Tomáš Perečko, tomas.perecko@ibp.cz) studies the effects of ionizing radiation on 1) hematopoiesis, and 2) the interaction of tumor cells with the immune system. The research is focused on the pharmacological modulation of hematopoiesis regeneration in acute radiation syndrome, the mechanisms of action of tested substances and the influence of potentially radioprotective substances on DNA damage repair. The laboratory also investigates the influence of the tumor microenvironment (hypoxia, inflammatory cytokines) on the interactions between tumor and immune cells affected by ionizing radiation. Pharmacological intervention (small molecules or biologics) in tumor–immune cell interaction may contribute to more effective and personalized cancer radiotherapy.

3. Laboratory of DNA-molecular complexes (Jiří Fajkus, fajkus@ibp.cz). The research group is focused on structure and evolution of telomeres and their roles in chromosome stability and plant speciation. The projects include the characterization of nucleoprotein composition of telomeres and telomerases, analysis of interactions of these components, and elucidation of their structure-function relationships.,. The research further includes alternative strategies of telomere maintenance and epigenetic mechanisms involved in regulation of gene expression, telomere homeostasis, and genome stability.

4. Laboratory of noncoding DNA and RNA (Petr Fajkus, fajkuspe@ibp.cz). The research group specializes in the study of non-coding RNA and DNA using modern approaches of comparative genomics and RNA biology with the aim of identifying functionally important RNA/DNA molecules and their involvement in regulatory mechanisms (mainly, but not only, in plant cells). For such functionally significant elements, we mainly examine their evolution, structure, expression level, mutual interactions and chemical modifications.