Nucleic Acid–Protein Interactions Laboratory (NAPI Lab)
Laboratoř interakcí nukleových kyselin s proteiny
Our lab focuses on understanding how the shape of DNA and its interactions with proteins influence genome function and stability.
Research Interest
Genome regulation is shaped not only by the DNA sequence itself, but also by its ability to form alternative secondary structures. These include G-quadruplexes, Z-DNA, cruciforms, and triplex DNA, which play important roles in processes such as transcription, DNA replication, and the maintenance of genome stability.
These non-canonical DNA structures are increasingly recognized as important regulatory elements in many biological processes. They are also closely linked to human diseases, including cancer, neurodegeneration, and aging. Transcription factors that specifically recognize structured DNA, such as p53 and its isoforms, act as key regulators of cellular stress responses and genome integrity.
Understanding how proteins, and moleculles selectively recognize and bind to these dynamic DNA structures is essential for uncovering the molecular mechanisms of genome regulation. At the same time, these structures represent promising therapeutic targets, offering new opportunities for the development of targeted approaches based on small molecules, natural compounds, nanobodies, or nucleic acids.
In our lab, we focus on understanding how DNA structure influences protein binding as well as interactions with small molecules, including natural compounds, and how these interactions contribute to genome regulation. We combine molecular biology, biophysics, bioinformatics, NMR spectroscopy, single molecule techniques, and genome wide analyses to study these processes.
Our research provides insight into how genome organization contributes to cellular function and disease, and it supports the development of new therapeutic strategies targeting non-canonical DNA structures.
Current Research Directions
- G‑quadruplex structures in nuclear & mitochondrial genomes – identification, variability, disease associations, structure analysis, therapeutic targeting.
- Protein–DNA interactions of major transcription factors – p53, p53 isoforms, IFI16, SG4 and others.
- DNA structures in neurodegeneration – G-quadruplex motifs as therapeutic targets.
- Noncanonical DNA motifs in cancer regulation – promoter G-quadruplexes, transcription, drug resistance.
- Small molecules, nanobodies, and aptamers targeting G4 DNA.
- Biophysical and computational analysis of DNA secondary structures.
Selected publications
- Cucchiarini A, Dobrovolná M, Brázda V, Mergny J-L. Analysis of quadruplex propensity of aptamer sequences. Nucleic Acids Res 2025;53:gkaf424. https://doi.org/10.1093/nar/gkaf424.
- Kledus F, Dobrovolná M, Mergny J-L, Brázda V. Asymmetric distribution of G-quadruplex forming sequences in genomes of retroviruses. Sci Rep 2025;15:76. https://doi.org/10.1038/s41598-024-82613-2.
- Kratochvilová L, Dinová A, Valková N, Dobrovolná M, Sánchez-Murcia PA, Brázda V. Chromatin Immunoprecipitation Reveals p53 Binding to G-Quadruplex DNA Sequences in Myeloid Leukemia Cell Lines. ACS Bio Med Chem Au 2025;5:283–98. https://doi.org/10.1021/acsbiomedchemau.4c00124.
- Vrtalová L, Dobrovolná M, Platero-Rochart D, Ptaszek AL, Brázda V, Sánchez-Murcia PA. Study on the Binding of Five Plant-Derived Secondary Metabolites to G-Quadruplexes. ACS Omega 2026;11:3096–107. https://doi.org/10.1021/acsomega.5c09032.
Recent publications
Call NCBI API with 5 recent V. Brazda publications - link
Bioniformatics softwares
DNA Analyser is a web-based server for nucleotide sequence analysis. It has been developed thanks to cooperation of Department of Informatics, Mendel’s University in Brno and Institute of Biophysics, Academy of Sciences of the Czech Republic. The aim of this service is to provide a free and user-friendly tool for studying DNA features with a focus on DNA local structures. The “Palindrome analyser”, which is capable to gather information about the presence of inverted repeats in DNA sequences, was established as a first tool. This was later followed by additional modules, including G4 Hunter, Z-DNA Hunter, and CPX Hunter, to expand the analysis of other important DNA motifs. Our unique application displays and analyses detailed information about different parameters of this important DNA feature including visualization, stability, and localization.
All web-based DNA secondary structure analysers can be found here: https://bioinformatics.ibp.cz
Palindrom analyser
Brázda V, Kolomazník J, Lýsek J, Hároníková L, Coufal J, Št’astný J. Palindrome analyser – A new web-based server for predicting and evaluating inverted repeats in nucleotide sequences. Biochem Biophys Res Commun 2016;478:1739–45. https://doi.org/10.1016/j.bbrc.2016.09.015
G4-Hunter
Brázda V, Kolomazník J, Lýsek J, Bartas M, Fojta M, Šťastný J, et al. G4Hunter web application: a web server for G-quadruplex prediction. Bioinformatics 2019;35:3493–5. https://doi.org/10.1093/bioinformatics/btz087
Z-DNA Hunter
Petrovič M, Bartas M, Garratt AN, Pečinka P, Dobrovolná M, Koňaříková K, et al. Z-DNA Hunter tool for straightforward detection of Z-DNA forming regions and a case study in Drosophila. NAR Genomics Bioinforma 2025;7:lqaf166. https://doi.org/10.1093/nargab/lqaf166
CpG Hunter
Bartas M, Petrovič M, Brázda V, Trenz O, Ďurčanský A, Šťastný J. CpX Hunter web tool allows high-throughput identification of CpG, CpA, CpT, and CpC islands: A case study in Drosophila genome. J Biol Chem 2025;301:108537. https://doi.org/10.1016/j.jbc.2025.108537
Group members
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Prof. Václav Brázda, Ph.D. Group leader
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Ing. Lenka Veselá Lab manager |
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Ing. Lucie Vrtalová Ph.D. student
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Michaela Dobrovolná Ph.D. student
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Ing. Libuše Kratochvilová Ph.D. student
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Mgr. Filip Kledus Ph.D. student
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Ing. Karolína Drápalová Ph.D. student
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Collaborations
- Jean-Louis Mergny - Laboratoire d’Optique et Biosciences, Ecole Polytechnique, CNRS, INSERM, Institut Polytechnique de Paris
- Seonghyun Lee & Rafael Han – Sungkyunkwan University, Korea
- Rieko Ohki – National Cancer Centre Japan
- Peter Podbevšek – Slovenian NMR Centre / CERIC
- Pedro Sanchez Murcia – Medical University of Graz
- Janusz Plavec & Maja Marušič – University of Ljubljana
- Richard Bowater & Stefan Bidula – University of East Anglia, UK
- Alberto Inga – University of Trento
- Thorsten Stiewe – University of Marburg
- Jean‑Christophe Bourdon – University of Dundee
- Johannes Grillari – Vienna, Austria
- Václav Honig - Virology Institute České Budějovice – Václav Honig
Funding
- GACR research projects (G4 DNA & p53 regulation)
- MŠMT – LUAKR25078 (CZ–Korea program)
- AVČR–JSPS Mobility (CZ–Japan)
- AVČR–Korea Mobility Program
- CERIC – Central European Research Infrastructure Consortium
- Institute of Biophysics internal support
- Erasmus+ student programs
Join Us
We welcome B.Sc., M.Sc., Ph.D. students and postdoctoral researchers interested in DNA structural biology and protein–DNA interactions.
Contact: vaclav@ibp.cz