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Lukáš Trantírek Research Group

Research Group Leader
Researcher ID
Phone: +420 54949 6476
E-mail: ,
Office:

Research areas

  • Cellular structural biology, (in-cell) NMR spectroscopy
  • Method development, stereochemistry of nucleic acids
  • Molecular engineering, biomolecular nanomachines, chemical signaling & metabolomics

Main objectives

  • Identification of novel therapeutic targets in a wide range of pathological states from cancer to developmental diseases.
  • Cellular structural biology of nucleic acids – method development
  • Epigenetic regulation of biomolecular function

Content of research

Selective targeting of non-canonical DNA regions within the human genome by small molecular weight ligandsG-quadruplexes (G4) are non-canonical DNA motifs overrepresented in telomeric DNA and the promoter regions of tightly regulated genes, such as oncogenes or genes involved in development regulation. The targeting of G4 within telomeres has been recognized as a new avenue of cancer chemotherapy as small molecular weight scaffolds that stabilize G4 in telomeres initiate senescence and apoptosis in otherwise immortal cancer cells. Unfortunately, a key limitation appearing almost universally among the existing scaffolds that target and stabilize G4 is their inability to bind G4 selectively compared to other DNA morphologies as well as to discriminate among distinct G4 structures. We set out to disentangle principles leading to development of molecular scaffolds that specifically target G4 in the particular gene. Our research elaborates on our recently acquired ability to resolve G4 polymorphs, identify G4 bioactive conformations and characterize their interactions using NMR spectroscopy and the state-of-the art methods of cellular structural biology.

Identification of the evolutionary conserved structural features of centromeric and telomeric DNA: The accurate transmission of a genome from one generation to another depends on the mechanism of cell division where each pair of replicated chromosomes, known as sister chromatids, are separated, and equally distributed to mother and daughter cells. The centromere is a specialized region of the eukaryotic chromosome that links sister chromatids. Loss of centromere identity in mitotic cells results in aneuploidy (loss or gain of chromosome), which may lead to cancer. Loss of centromere identity in meiotic cells leads to spontaneous abortion or developmental defects.By studying evolutionary conserved structural features in the centromeric and evolutionary related telomeric DNA, we are trying to identify epigenetic universal hallmarks, which identify the centromere position in a newly replicated genome.

Notable part of our research focuses on: i) development of methods for structural analysis of nucleic acids in vitro as well as in complex environment of living cells, ii) investigation of mechanisms of chemical signaling, and iii) principles of epigenetic regulation of gene expression.

i/motif/trant

list / cards

Name and position

E-mail

Phone

Lukáš Trantírek, Ph.D.
Research Group Leader
+420 54949 6476
Silvie Trantírková, Ph.D.
Senior Researcher
+420 54949 3828
Michael Andäng, Ph.D.
Senior researcher
+420 54949 5992
Jan Ryneš, Ph.D.
Postdoctoral Fellow
+420 54949 5992
Barbora El Ghannamová
Technician
+420 54949 7717
Zuzana Šrámková
PhD Student
+420 54949 7832
Šimon Džatko
Student
+420 54949 7832
Michaela Krafčíková
Student
+420 54949 7832
Martin Gajarský
Student
+420 54949 7832
Helena Anna Dagmar Johard, Ph.D.
+420 54949 7832
Tereza Chmelíková
Student
Barbora Zobačová
Student
Kateřina Beková
Lucie Marková
Pavlína Víšková
Student
Jakub Harnoš
Hana Konečná
Specialist
+420 54949 5050
Daniel Krafčík
Student
Martina Lenarčič Živković
Eva Maturová

SELECTED PUBLICATIONS

2017

  • GROCHALOVA, M; KONECNA, H; STEJSKAL, K; POTESIL, D; FRIDRICHOVA, D; SRBOVA, E; ORNEROVA, K; ZDRAHAL, Z, 2017:Deep coverage of the beer proteome. JOURNAL OF PROTEOMICS 162 , p. 119 - 124.
  • GUDERNOVA, I; FOLDYNOVA-TRANTIRKOVA, S; EL GHANNAMOVA, B; FAFILEK, B; VARECHA, M; BALEK, L; HRUBA, E; JONATOVA, L; JELINKOVA, I; KUNOVA BOSAKOVA, M; TRANTIREK, L; MAYER; J; KREJCI, P, 2017:One reporter for in-cell activity profiling of majority of protein kinase oncogenes. eLife 6 (14)
  • KEJNOVSKA, I; BEDNAROVA, K; RENCIUK, D; DVORAKOVA, Z; SKOLAKOVA, P; TRANTIREK, L; FIALA, R; VORLICKOVA, M; SAGI, J, 2017:Clustered abasic lesions profoundly change the structure and stability of human telomeric G-quadruplexes. NUCLEIC ACIDS RESEARCH 45 (8), p. 4294 - 4305.
  • LINKE, F; HARENBERG, M; NIETERT, M M; ZAUNIG, S; VON BONIN, F; ARLT, A; SZCZEPANOWSKI, M; WEICH, H A; LUTZ S; DULLIN, C; JANOVSKÁ, P; KRAFČÍKOVÁ, M; TRANTÍREK, L; OVESNÁ, P; KLAPPER, W; BEISSBARTH, T; ALVES, F; BRYJA, V; TRÜMPER, L; WILTING, J, KUBE, D, 2017:Microenvironmental interactions between endothelial and lymphoma cells: a role for the canonical WNT pathway in Hodgkin lymphoma. Leukemia 31 (2), p. 361 - 372.

2016

  • RYNES, J; HARNOS, J; BRYJA, V; KREJCI, P; TRANTIRKOVA, S; TRANTIREK, L, 2016:Modulation of cell signaling via interfering specific protein-protein interactions of a hub scaffold protein. FEBS JOURNAL 283 , p. 229 - 229.
  • SLANINOVA, V; KRAFCIKOVA, M; PEREZ-GOMEZ, R; STEFFAL, P; TRANTIREK, L; BRAY, SJ; KREJCI, A, 2016:Notch stimulates growth by direct regulation of genes involved in the control of glycolysis and the tricarboxylic acid cycle. OPEN BIOLOGY 6 (2)
  • TRISKOVA, I; FIALA, R; TRNKOVA, L, 2016:Redox Processes of Guanine Moieties in DNA Heptamers Related to Hydrogen Evolution. ELECTROANALYSIS 28 (11), p. 2841 - 2848.
  • VAVRINSKA, A; ZELINKA, J; SEBERA, J; SYCHROVSKY, V; FIALA, R; BOELENS, R; SKLENAR, V; TRANTIREK, L, 2016:Impact of nucleic acid self-alignment in a strong magnetic field on the interpretation of indirect spin-spin interactions (vol 64, pg 53, 2016). JOURNAL OF BIOMOLECULAR NMR 65 (1), p. 49 - 49.
  • VAVRINSKA, A; ZELINKA, J; SEBERA, J; SYCHROVSKY, V; FIALA, R; BOELENS, R; SKLENAR, V; TRANTIREK, L, 2016:Impact of nucleic acid self-alignment in a strong magnetic field on the interpretation of indirect spin-spin interactions. JOURNAL OF BIOMOLECULAR NMR 64 (1), p. 53 - 62.

2015

  • STADLBAUER, P; KUHROVA, P; BANAS, P; KOCA, J; BUSSI, G; TRANTIREK, L; OTYEPKA, M; SPONER, J, 2015:Hairpins participating in folding of human telomeric sequence quadruplexes studied by standard and T-REMD simulations. NUCLEIC ACIDS RESEARCH 43 (20), p. 9626 - 9644.
  • ZANNI, G; DI MARTINO, E; OMELYANENKO, A; ANDANG, M; DELLE, U; ELMROTH, K; BLOMGREN, K, 2015:Lithium increases proliferation of hippocampal neural stem/progenitor cells and rescues irradiation-induced cell cycle arrest in vitro. ONCOTARGET 6 (35), p. 37083 - 37097.

2014

  • BERNATIK, O; SEDOVA, K; SCHILLE, C; GANJI, RS; CERVENKA, I; TRANTIREK, L; SCHAMBONY, A; ZDRAHAL, Z; BRYJA, V, 2014:Functional Analysis of Dishevelled-3 Phosphorylation Identifies Distinct Mechanisms Driven by Casein Kinase 1 epsilon and Frizzled5. JOURNAL OF BIOLOGICAL CHEMISTRY 289 (34), p. 23520 - 23533.

GRANTY

  • Environmentally Controlled Polymorphism of non-B DNA structures (322104), FP7- People - Marie Curie actions - CIG, 2012 - 2016
  • Targeting ion fluxes affecting nutrient transport in glioma cancer stem cells- Novel targets selective for therapy-resistant immature cancer cells (GA15-20818S), Czech Science Foundation - Standard Grants, 2015 - 2018
  • Towards selective targeting of DNA G-quadruplexes by small molecular weight ligands within the human genome (4SGA8580), South Moravian Region - SoMoPro, 2014 - 2016
  • Cellular Structural Biology of non-B DNA Motifs in Human Genome (2535), EMBO (European Molecular Biology Organization ) grants, 2013 - 2015
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