Do you know…

• … the scientists in CEITEC will be researching what happens in the brain when a human has realized that they have made a mistake?
• … there will be nearly 800 scientists in CEITEC?
• …  in CEITEC we will be researching how the brain works and why some people are motivated and others are not?
• … thanks to CEITEC most of the diagnostic methods will be cheaper, faster and more comfortable for the patients?
• … 63 research teams will be created in CEITEC?
• … there will be 7 research programmes in CEITEC?
• …  there will be more than 1,000 modern instruments in CEITEC?
• … more than 31,000 m2 of new infrastructure will be built in CEITEC?
• … more than 1,500 students will use the CEITEC infrastructure per year?
• … there will be 10 shared laboratories created in CEITEC?
• … CEITEC has 6 partners?
• … work will be carried out on self-cleaning surfaces in CEITEC?
• … CEITEC will co-operate closely with the industrial sector?
• … there will also be international scientists working in CEITEC?
• … CEITEC will support the international mobility of scientists?
• … the scientists in CEITEC are developing a subdermal chip which will analyse some life functions  and will inform doctors from a distance?
• … the scientists in CEITEC are working on the development of a device which will enable physiotherapy from a distance?
• … the scientists at CEITEC are working on the development of biosensors?
• … CEITEC will be created in the south-Moravian city of Brno?

Prof. RNDr. Michaela Vorlíčková, DrSc.
Research Group Leader

THEMATIC RESEARCH FOCUS

RESEARCH AREAS

• Studies of the conformational properties of genomic DNA fragments important from biological and medical point of view
• Investigations into the structure and interactions of biomacromolecules and their relation to the functions of living systems, disease and therapy

MAIN OBJECTIVES

• To map the conformational properties of DNA sequence motifs occurring in important regions of the human genome.
• To characterise the physico-chemical properties of non-B DNA structures, chemical alterations in DNA, and other external factors on their stability, dynamics and recognition by proteins.

CONTENT OF RESEARCH

Depending on sequence, DNA can adopt various secondary structures distinct from the classical double helix of Watson and Crick. The conformational distinctions include double helix handedness, orientation of strands, type of base pairing, and the number of associated strands. These unusual secondary structures are frequently implicated in various biological functions or diseases. At present the most frequently studied unusual secondary structures are quadruplexes.

There are numerous regions in the human genome prone to form quadruplexes. They frequently occur in gene promoters and control their function. We focus on quadruplexes formed by telomeric DNA and DNA of selected oncogenes. The quadruplexes formed in telomers influence aging and cancer, and thus have become targets for the design of anticancer agents.

A further hot topic is currently the reprogramming of differentiated cells into pluripotent stem cells. The most important pluripotency determinants, c-myc and oct4 genes, contain a DNA sequence in their promotor regions that is capable of forming quadruplex. Our expertise in the prediction of quadruplex formation, in their experimental detection and characterisation in relation to their function will become the basis for perspective development of targeted therapy for cancer and other diseases.

KEY RESEARCH EQUIPMENT

PLANNED RESEARCH INFRASTRUCTURE

Technology Units

CD spectroscopy of nucleic acids and proteins

CURRENT RESEARCH INFRASTRUCTURE

The research group is currently equipped with UV/VIS absorption spectrophotometer Varian Cary 4000; Jobin-Yvon Mark VI CD spectrometers.

MAIN PROJECTS

• Biophysical Properties of Biologically and Medically Important Regions of Human DNA (IAA100040701), Academy of Sciences of the Czech Republic, 2007-2011, M. Vorličkova, Institute of Biophysics AS CR.
• Biophysics and bioinformatics of genomic DNA fragments very rich in guanine and adenine (IAA500040903), Academy of Sciences of the Czech Republic, 2009-2013, J. Kypr, Institute of Biophysics AS CR, V. Sklenař, Masaryk University.
• Formation and dynamics of nucleic acid motifs involved in regulation of gene expression (GA202/09/0193), Czech Science Foundation, 2009-2013, J. Štěpanek, Charles University in Prague, I. Rosenberg, Institute of Organic Chemistry and Biochemistry AS CR, J. Homola, Institute of Photonics and Electronics AS CR, M. Vorličkova, Institute of Biophysics AS CR.

SELECTED PUBLICATIONS

• KYPR, J., KEJNOVSKA, I., RENCIUK, D., VORLICKOVA, M. Circular dichroism and conformational polymorphism of DNA. Nucleic Acids Res. 2009, 37(6), p. 1713-1725.
• RENCIUK, D., KEJNOVSKA, I., SKOLAKOVA, P., BEDNAROVA, K., MOTLOVA, J., VORLICKOVA, M. Arrangements of human telomere DNA quadruplex in physiologically relevant K+ solutions. Nucleic Acids Res. 2009, 37, p. 6625-6634.
• NEJEDLY, K., CHLADKOVA, J., VORLICKOVA, M., HRABCOVA, I., KYPR, J. Mapping the B-A conformational transition along plasmid DNA. Nucleic Acids Res. 2005, 33(1), 8p.
• VORLICKOVA, M., CHLADKOVA, J., KEJNOVSKA, I., FIALOVA, M., KYPR, J. Guanine tetraplex topology of human telomere DNA is governed by the number of (TTAGGG) repeal. Nucleic Acids Res. 2005, 33, p. 5851-5860.
• FOJTIK, P., KEJNOVSKA, I., VORLICKOVA, M. The guanine-rich fragile X chromosome repeats are reluctant to form tetraplexes.Nucleic Acids Res. 2004, 32, p. 298-306.