Biophysics of Nucleic Acids
Finished projects
Role of guanine quadruplexes in chromatin architecture mediated by CTCF protein
Project ID code: 22-29738S
Provider: GAČR
Years: 2022 - 2024
Solver: Mgr. Daniel Renčiuk Ph.D.
Regulation of gene expression in Eukaryotes, mediated by promoter-enhancer interactions, is
partially realized by organization of these regulatory elements into so called topologicallyassociating
domains (TAD). The probability of the interaction and, subsequently, the
employment of the enhancer regulatory machinery, is significantly higher within one TAD than
within different ones. Key component of the boundaries between individual TADs is the CTCF
protein bound to cohesin complex. Recently it was observed using bioinformatics tools that the
TAD boundaries well correlate with the position of potential quadruplex-forming sites (G4). G4
are secondary structures of nucleic acids, based on pairing of four guanine residues through
Hoogsteen hydrogen bonds. G4 existence in vivo was recently confirmed. In the project, we will
study the interaction of different G4 types with CTCF protein and its variants by following direct
interaction of purified molecules, using molecular biology and biophysics methods, and by using
reporter systems in cell-based models.
The role of guanine quadruplexes in the RNA genome of tick-borne encephalitis virus, causal agent of severe neuroinfections
Project ID code: 20-20229S
Provider: GAČR
Years: 2020 - 2022
Solver: Mgr. Daniel Renčiuk Ph.D.
Abstract: Guanine quadruplexes (G4) represent structurally diverse group of unusual conformations of
nucleic acids. Recently, their occurrence in vivo and some of their cellular roles was reported.
RNA quadruplexes are very stable, even in comparison to DNA, which supports their formation
in vivo and their involvement in cellular processes. They were reported in some RNA viruses,
for example retroviruses or flaviviruses. The Flaviviridae family comprises viruses with singlestranded
RNA genome, which are usually responsible for severe neural infections, like tickborne
encephalitis virus (TBEV). In the project, we will identify and, using biophysical
techniques, characterize quadruplexes in the TBEV genome. Subsequently, by studying the
influence of G4-specific mutants and small-molecule ligands, as well as by direct quadruplex
visualisation in the TBEV genome, we will assist in clarifying the role of quadruplexes in the
TBEV replication cycle. The data obtained in this project will expand the knowledge of TBEV
pathogenesis and might suggest future directions of therapy of TBEV infections.
The goal: Prediction, identification and biophysical characterization of guanine quadruplexes (G4) in the
RNA genome of the tick-borne encephalitis virus and clarifying the G4 role in viral replication
cycle by studies of G4-specific viral mutants and by a visualization of the G4 in infected cell
cultures.
Tetrastranded arrangements of DNA and their interactions
Project ID code: 19-17063S
Provider: GA ČR
Years: 2019 - 2021
Solver: prof. RNDr. Michaela Vorlíčková, DrSc.
Tetra-stranded structures of nucleic acids, namely guanine quadruplexes and cytosine i-motifs,
are, due to their numerous regulatory functions in vivo, in the spotlight of the current molecular
biology. Our observations indicate, in accordance with literature, that the conformational
portfolio of such structures is much broader than expected based on standard search
algorithms. These “less apparent” tetra-stranded structures may exist due to various base or
sequence substitution effects along the strands and, as such, they may represent a fine-tuned
regulation of cellular processes. In the project, we will characterize, using biophysical and
molecular biological techniques, these less apparent tetra-stranded conformations, their
interactions and some of their functional manifestations. In view of regulatory role of these
structures, the identification of small variations in primary sequence that dramatically modulate
secondary structure, either positively or negatively, has substantial importance in the context of
recently emerging field of genome manipulations.
Polymorphic G-quadruplexes in gene promoters
Project ID code: 17-12075S
Provider: GA ČR
Years: 2017 - 2019
Identification and biophysical characterization of regulatory DNA elements of the gene for main pluripotency factor POU5F1
Project ID code: 17-19170Y
Provider: GA ČR
Years: 2017 - 2019
Nucleic acid regulatory sequences - polymorphism, dynamics, and interactions
Project ID code: 15-06785S
Provider: GA ČR
Years: 2015 - 2017
Regulation of the embryonic stem cell pluripotency factor Oct4 via guanine quadruplex in its promoter
Project ID code: 14-33947P
Provider: GA ČR
Years: 2014 - 2016
Evolutionary conserved structural features of centromeric and telomeric DNA
Project ID code: 13-28310S
Provider: GA ČR
Years: 2013 - 2016
DNA quadruplexes in the human genome associated with diseases and aging
Project ID code: P205-12-0466
Provider: GA ČR
Years: 2012 - 2016
Biophysics and bioinformatics of genomic DNA fragments very rich in guanine and adenine
Project ID code: IAA500040903
Provider: GA AV
Years: 2009 - 2013
Formation and dynamics of nucleic acid motifs involved in regulation of gene expression
Project ID code: GA202/09/0193
Provider: GA ČR
Years: 2009 - 2013
Biophysical properties of biologically and medically important regions of human DNA
Project ID code: IAA100040701
Provider: GA AV
Years: 2007 - 2011
Biophysics and bioinformatics of human genome regions with an extreme nucleotide distribution
Project ID code: GA202/07/0094
Provider: GA ČR
Years: 2007 - 2009
Tetraplexes in the human genome
Project ID code: GA204/07/0057
Provider: GA ČR
Years: 2007 - 2009
Pathological microsatelite expansion in the human genome
Project ID code: NR9147
Provider: MZ
Years: 2007 - 2009
Biophysical properties of (guanine+cytosine) and (adenine+thymine) regions in the DNA molecules of human chromosomes
Project ID code: IAA1004201
Provider: GA AV
Years: 2002 - 2006
Tetraplexes of DNA and their occurrence in the human genome
Project ID code: IAA4004201
Provider: GA AV
Years: 2002 - 2006
Conformational transitions in plasmid DNA.
Project ID code: IAA1004301
Provider: GA AV
Years: 2003 - 2005
Development of a method for prediction of the pathological trinucleotide repeat expansion in the human genome
Project ID code: NM7634
Provider: MZ
Years: 2003 - 2005
Conformational polymorphism of DNA molecules containing trinucleotide repeats associated with genetic diseases
Project ID code: 204/01/0561
Provider: GA ČR
Years: 2001 - 2003