Department of Structural Chemistry and Biology of Nucleic Acids
Dr. Dorota Magner,
Dr. Marta Soszyńska-Jóźwiak,
Dr. Joanna Sarzyńska,
Grażyna Dominiak MSc
Tomasz Czapik MSc
Marta Szabat MSc,
Calculators of thermodynamic parameters.
structure, dynamic and function of nucleic acids, modified oligonucleotides, thermodynamics of nucleic acids, posttranscriptional RNA folding, antisense oligonucleotides, alternative splicing, oligonucleotide microarrays, microarray mapping, conformational fixed nucleic acids, retroviral RNA, retrotransposons, RNA therapeutics, chemistry and molecular biology of RNA, structural bioinformatics, nucleic acids structure calculation, trinucleotide repeats, RNA bulged duplexes, restricted conformation of modified purine nucleosides
The outlines of research group are best described by its name Department of Structural Chemistry and Biology of Nucleic Acids. We are interested in investigations of structural chemistry and biology of RNAs based on experiences in chemical synthesis of oligonucleotides, studies of structure and interactions of RNAs, as well as research of nucleic acids thermodynamics. Compilation of those approaches is applied to influence the structure and functional activities of RNAs, including pathogenic RNAs related with human diseases. In the performed studies, RNA is a tool as well as target of therapeutic treatment. The chemical syntheses of oligonucleotides mostly concern incorporation into oligomer structurally and functionally defined nucleotides residues. The best example of that modified oligonucleotides are oligomers with syn or C3'-endo fixed nucleotide residues.
RNA structure related studies focus on two issues. First, it is determination of the secondary structure and interactions of RNA. A new method for determination of RNA secondary structure based on isoenergetic microarrays was developed. Microarrays mapping was successfully used to solve secondary structures of many RNAs as well as RNA/protein and RNA1/protein/RNA2 complexes. The second category of investigations is based on application of modified oligonucleotides with conformationally restricted (syn and C3'-endo) nucleotide residues to study hydrogen bonding, stacking and electrostatic interactions within RNA. The thermodynamic studies were mostly focused on developing thermodynamic rules of binding the modified oligonucleotides probes of isoenergetic microarrays to target RNAs.
In particular, the research focused on the influence of locked nucleic acids (LNA) on thermodynamic stabilities of RNA/LNA-2'-O-methyl-RNA duplexes. It was important to evaluate the influence of LNA residues on thermodynamic stability of complementary and mismatched LNA-2'-O-methyl-RNA/RNA duplexes with LNA residues placed at various positions within the duplex. Based on thermodynamic data, the nearest neighbor thermodynamic parameters of 2'-O-methylRNA/RNA and LNA-2'-O-methylRNA/RNA duplexes formations were determined and applied to prepare the calculators available on this website.
Recently, we are also very much involve on developing a new methods of the allele-selective degradation of pathogenic RNA. Both methods are based on different thermodynamic hybridization of antisense oligonucleotides with mutated and wild type forms of target RNA. First of the new methods is based on simultaneous application of two antisense oligonucleotides. One on them binds to mutated form of RNA and induce it degradation whereas second oligonucleotide preferentially bind to wild type RNA and inhibit it degradation. Second method is based on ability of RNase H cleavage of RNA caring different structural motifs within antisense oligonucleotide/target RNA duplex. Structural motifs form by the same antisense oligonucleotide with mutated RNA result in cleavage whereas structural motif created due to interaction with wild type RNA diminish or inhibit of RNA degradation.
Current research activity:
Most important research achievements:
Current research projects:
Conformationally restricted oligonucleotides. Studies of the structure and structural determinants interactions of RNAs. UMO-2013/08/A/ST5/00295, 28 August 2013 -27 August 2018 r, NCN Maestro project.
1/ I. Yildirim, S.D. Kennedy, H.A. Stern, J.M. Hart, R. Kierzek and D.H. Turner
2/ A. Kiliszek, R. Kierzek, W.J. Krzyzosiak, W. Rypniewski
3/ W.N. Moss, L.I. Dela-Moss, E. Kierzek, R. Kierzek, S.F. Priore, D.H. Turner
4/ S.D. Kennedy, R. Kierzek, D.H. Turner
5/ Y. Zhou, E. Kierzek, Z.P. Loo, M. Antonio, Y.H. Yau, Y.W. Chuah, S. Geifman-Shochat, R. Kierzek and G. Chen
6/ S.F. Priore, E. Kierzek, R.Kierzek, J.R. Baman; W.N. Moss; L.I. Dela-Moss, D.H. Turner
7/ E. Kierzek, M. Malgowska, J. Lisowiec, D.H. Turner, Z. Gdaniec and R. Kierzek
8/ D.E. Condon, I. Yildirim, S.D. Kennedy, B.C. Mort, R. Kierzek and D. H. Turner
9/P. Sripakdeevong, M. Cevec, A.T. Chang, M.C. Erat, M. Ziegeler, Q. Zhao, G.E Fox, X. Gao, S.D. Kennedy, R. Kierzek, E.P. Nikonowicz, H. Schwalbe, R.K. O’Sigel, D.H. Turner and R. Das
10/ M. Malgowska, D. Gudanis, R. Kierzek, E. Wyszko, V. Gabelica, Z. Gdaniec
11/ I. Yildirim, E. Kierzek, R. Kierzek, G. Schatz
12/ R. Kierzek, D.H. Turner, E. Kierzek
13/ J. Lisowiec, D. Magner, E. Kierzek, E. Lenatrowicz, R. Kierzek
14/ D. Condon, S. Kennedy, B. Mort, R. Kierzek, I. Yildirim, D.H. Turner
15/ D. Magner, E. Biala, J. Lisowiec-Wachnicka, E. Kierzek, R. Kierzek,
16/ M. Szabat; T. Pedzinski, T. Czapik, E. Kierzek, R. Kierzek,
17/ E. Lenartowicz, J. Kesy, A. Ruszkowska, M. Soszynska-Jozwiak, P. Michalak, W.N. Moss, D.H. Turner, R. Kierzek, E. Kierzek,
18/ W. Kotkowiak, A. Pasternak, R. Kierzek,
19/ M. Szabat, D. Gudanis, W. Kotkowiak, Z. Gdaniec, R. Kierzek, A. Pasternak,
20/ D. Gudanis, L. Popenda, K. Szpotkowski, R. Kierzek, Z. Gdaniec,
21/ E. Lenartowicz, A. Nogales, E. Kierzek, R. Kierzek, L. Martinez-Sobrido, D.H. Turner,
22/ A. Ruszkowska, E. Lenartowicz, W.N. Moss, R. Kierzek, E. Kierzek,