Department of Cell Biology and Radiobiology

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

 

Research Keywords

Chromatin Structure & Function in physiological and pathological processes

— higher-order chromatin structure in regulation of fundamental nuclear processes like transcription, replication, differentiation, DNA repair etc.; chromatin dynamics and epigenetic modifications; histone code

— higher-order chromatin structure in development of chromosomal aberrations and carcinogenesis (currently mostly focused on):

·         molecular pathogenesis of leukemia, e.g. acute promyelocytic leukemia (APL)

·         mechanism of recurrent chromosomal aberrations in myelodysplastic syndromes (MDS)

— telomere biology

— HMG proteins

DNA damage and repair, maintenance of the genome stability— mechanisms of DNA double strand break (DSB) induction, repair, and misrepair; influence of higher-order chromatin on DSB induction and repair efficiency; DSB repair during cell cycle, development, and pathological processes; unstable repeat sequences, trinucleotide repeat expansion diseases (MD, HD)

Radiobiology

— mechanisms of induction and  repair of DSBs (see the paragraph above) upon the action of different kinds of ionizing radiations (e.g. high-LET and low-LET)

 — complex cell response to different kinds of ionizing radiations

— radiotherapy and its new possibilities: proton therapy and ion-beam cancer therapy

— tumor cell radiosensitization and normal cell radioprotection; radiosensitizing effect of metal nanoparticles and its mechanism; radioprotectives

— chromosomal translocations and their mechanism

— radio-hematology: experimental hematology, pharmacological radioprotection, adenosine receptors, antiphlogistic drugs, cyclooxygenase inhibitors

Nanomedicine- see above

Carcinogenesis- see above

Plant molecular biology

 

Methods- cell culture, fluorescent in situ hybridization (FISH), immuno-FISH, immuno-cytochemistry, Western blotting, PCR, qRT-PCR, cell transfection, gene silencing, high-resolution confocal microscopy, living-cell microscopy, image analysis, micro-induction of DNA double-strand breaks at a subnuclear level, g-irradiation, proton and ion-beam irradiation (at cooperating institutes), fractionated irradiation

 

 

Research profile

In the Department of Radiobiology and Cell Biology, we look into a broad scale of questions associated with a complex response of cells to irradiation with different kinds of ionizing radiations, as well as the principles of chromatin organization in nuclei of eukaryotic cells and relationships between this structure and chromatin function upon physiological and pathological conditions. The Department is organized in four research groups:

 

1. Laboratory of Chromatin Function, Damage, and Repair(Martin Falk, falk@ibp.cz) investigates the effects of different kinds of ionizing radiations (, accelerated protons and heavy ions) 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 carcinogenesis. 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). 

Research Keywords:

·         relationship between the higher-order chromatin structure and fundamental nuclear processes

·         relationship between the higher-order chromatin structure and DNA damage induction by ionizing radiations of different qualities (e.g. high-LET vs. low-LET)

·         cell response to ION-BEAM CANCER THERAPY

·         radiosensitizing effect of metal NANOPARTICLES

·         mechanism of DSB repair in the context of higher-order chromatin structure

·         mechanism of how CHROMOSOMAL ABERRATIONS are formed

·         structural and functional base of recurrent chromosomal deletions and CHROMOTHRIPSIS in Myelodysplastic syndromes (MDS)

·         molecular pathogenesis of acute promyelocytic leukemia (APL)

·         role of REPLICATION STRESS in DNA damage and carcinogenesis

 

2. Laboratory of Experimental Hematology

The group studies the effects of adenosine receptor antagonists and cyclooxygenase inhibitors on the hematopoiesis, the influence of these compounds on the cell regeneration upon the conditions of the acute radiation syndrome, the mechanisms of action of these compounds on genetically engineered mice, the effects of radioprotective agents on the repair of DNA double strand breaks.

 

3. Laboratory of DNA-molecular complexes

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 telomere components, elucidation of structure-function relationships of telomerase subdomains, and analysis of alternative strategies of telomere maintenance. The group is also interested in epigenetic mechanisms involved in regulation of gene expression, telomere homeostasis, and genome stability. 

 

4. Laboratory of Analysis of Chromosomal Proteins

Laboratory of Analysis of Chromosomal Proteins (Michal Štros, stros@ibp.cz) concerns itself with the interactions between different chromatin components that are important in the context of the DNA repair, genome stability, and effects of medical drugs (that bind to chromatin). Mainly analyzed are the interactions between HMGB proteins with various DNA structures, nucleosomes, and biologically important proteins, like histones, tumor suppressors (p53/p73), topoisomerases, and telomerases.