title: Determining Omics spatiotemporal dimensions using exciting new nanoscopy techniques to assess complex cell responses to DNA damage: part B--structuromics.
abstract: Recent groundbreaking developments in Omics and bioinformatics have generated new hope for overcoming the complexity and variability of (radio)biological systems while simultaneously shedding more light on fundamental radiobiological questions that have remained unanswered for decades. In the era of Omics, our knowledge of how genes and dozens of proteins interact in the frame of complex signaling and repair pathways (or, rather, networks) to preserve the integrity of the genome has been rapidly expanding. Nevertheless, these functional networks must be observed with strong correspondence to the cell nucleus, which is the main target of ionizing radiation. Information regarding these intricate processes cannot be achieved using high-throughput Omics approaches alone; it requires sophisticated structural probing and imaging. In the first part of this review, the article "Giving Omics Spatiotemporal Dimensions Using Exciting New Nanoscopy Techniques to Assess Complex Cell Responses to DNA Damage: Part A--Radiomics," we showed the development of different Omics solutions and how they are contributing to a better understanding of cellular radiation response. In this Part B we show how high-resolution confocal microscopy as well as novel approaches of molecular localization nanoscopy fill the gaps to successfully place Omics data in the context of space and time. The dynamics of double-strand breaks during repair processes and chromosomal rearrangements at the microscale correlated to aberration induction are explained. For the first time we visualize pan-nuclear nucleosomal rearrangements and clustering at the nanoscale during repair processes. Finally, we introduce a novel method of specific chromatin nanotargeting based on a computer database search of uniquely binding oligonucleotide combinations (COMBO-FISH). With these challenging techniques on hand, we speculate future perspectives that may combine specific COMBO-FISH nanoprobing and structural nanoscopy to observe structure-function correlations in living cells in real-time. Thus, the Omics networks obtained from function analyses may be enriched by real-time visualization of Structuromics.
authors: Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
authors: Martin
authors: M
authors: Falk
authors: Kirchhoff Institute for Physics, University of Heidelberg, Heidelberg, Germany.
authors: Michael
authors: M
authors: Hausmann
authors: Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
authors: Emílie
authors: E
authors: Lukášová
authors: Kirchhoff Institute for Physics, University of Heidelberg, Heidelberg, Germany; Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Heidelberg, Germany.
authors: Abin
authors: A
authors: Biswas
authors: Department of Radiation Oncology, University Medical Center Mannheim, Kirchhoff Institute for Physics, University of Heidelberg, Heidelberg, Germany.
authors: Georg
authors: G
authors: Hildenbrand
authors: Nuclear Physics Institute, Academy of Sciences of the Czech Republic, Rez, Czech Republic.
authors: Marie
authors: M
authors: Davídková
authors: Joint Institute for Nuclear Research, Dubna, Moscow, Russia.
authors: Evgeny
authors: E
authors: Krasavin
authors: Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
authors: Zdeněk
authors: Z
authors: Kleibl
authors: Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
authors: Iva
authors: I
authors: Falková
authors: Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic; Joint Institute for Nuclear Research, Dubna, Moscow, Russia; Institute of Chemical Technology Prague, Prague, Czech Republic.
authors: Lucie
authors: L
authors: Ježková
authors: Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
authors: Lenka
authors: L
authors: Štefančíková
authors: Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
authors: Jan
authors: J
authors: Ševčík
authors: Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
authors: Michal
authors: M
authors: Hofer
authors: Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
authors: Alena
authors: A
authors: Bačíková
authors: Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic; Centre for Biomedical Image Analysis, Faculty of Informatics, Masaryk University, Brno, Czech Republic.
authors: Pavel
authors: P
authors: Matula
authors: Joint Institute for Nuclear Research, Dubna, Moscow, Russia.
authors: Alla
authors: A
authors: Boreyko
authors: Nuclear Physics Institute, Academy of Sciences of the Czech Republic, Rez, Czech Republic.
authors: Jana
authors: J
authors: Vachelová
authors: Nuclear Physics Institute, Academy of Sciences of the Czech Republic, Rez, Czech Republic; Proton Therapy Center, Prague, Czech Republic.
authors: Anna
authors: A
authors: Michaelidisová
authors: Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
authors: Stanislav
authors: S
authors: Kozubek
mesh_terms: D002467:Cell Nucleus / Q000528:radiation effects*; D002843:Chromatin / Q000235:genetics / Q000528:radiation effects; D004247:DNA / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D004260:DNA Repair / Q000235:genetics*; D016678:Genome / Q000235:genetics; D042822:Genomic Instability; D006801:Humans; D018613:Microscopy, Confocal; D011839:Radiation, Ionizing; D014178:Translocation, Genetic / Q000235:genetics / Q000528:radiation effects*
chemical_list: D002843:Chromatin; D004247:DNA