Hanna Gracz

The Institute of Bioorganic Chemistry Polish Academy of Sciences (IBCH PAS) was established almost 25 years ago, but its origins date back to 1969 when the Department of Stereochemistry of Natural Products was brought into being at the Institute of Organic Chemistry PAS. In 1980, the Department of Stereochemistry of Natural Products was transformed into an independent entity – Department of Bioorganic Chemistry PAS. In 1988, the latter was finally converted into the Institute of Bioorganic Chemistry Polish Academy of Sciences. Today, together with the affiliated Poznan Supercomputing and Networking Center, the IBCH PAS has more than 460 staff members, including 80 research scientists (33 Professors). In addition, about 80 Ph.D. students are currently involved in the research projects conducted at IBCH PAS.

The scientific portfolio of the Institute has many dimensions: synthesis and structure of natural products, in particular nucleic acids and their components; biochemistry, molecular and structural biology of model biological systems, genetic engineering, genomics and bioinformatics. IBCH PAS is authorized to confer the degree of doctor and habilitated doctor in chemistry and biochemistry.

The Institute is organized into 12 research departments and 10 research groups. Within the structure of the Institute, there are also other crucial units associated: the PAS Poznan Science Center, Scientific Publishers, Guest Rooms ( I like this place), and Library. In the latest years, the Institute in collaboration with the Poznan University of Technology have created a European Center for Bioinformatics and Genomics, a unique unit in Poland.

I am affiliated currently during this visit with  Biomolecular  NMR Group  which is a part  of  Laboratory of Structural Chemistry of Nucleic Acids. The head of the BioNMR group is: Prof. Zofia Gdaniec (third from the right), and the head of the Structural Chemistry of Nucleic Acids Group is  Prof. Ryszard Adamiak (third from the left).

Major  results from the Structural Chemistry of Nucleic Acids Group are:

• 1975-1980: New protective groups in oligoribonucleotide synthesis, first total synthesis of tRNA anticodon loop and arm heptanucleotide containing hypermodified nucleosidet6A.
• 1980-1985: Finding of left-handed RNA helix on the ologonucleotide level.
• 1985-1990: Elucidation of the mechanism of side-reactions in oligonucleotides synthesis via phoshotriester method, finding of nucleoside pyridinium salts and their photochemistry; photochemical formation of luminarosie, very potent nucleoside fluorophore.
• 1990-1995: First solid-phase synthesis of RNA fragments containing hypermodified nucleoside.
• 1995-2000: Determining solution and crystal structures of non-canonical RNAs containing alternating CG base pairs.
• 2000-2005: Determining NMR structure of left-handed RNA (Z-RNA) (first biomolecular fragment determined under concentrated salt conditions).
• On a picture above, Prof. Ryszard Adamiak with crystal  icon of Z-RNA during a celebration last week -Maestro Grant from EU has been awarded to Him (see on a cake).
• Design and implementation of the first Polish NMR virtual laboratory NMR.
• 2005-2010: Finding structural polymorphism of the 5′-end of the HIV-2 leader RNA, development of the RNA FRABASE server for search and analysis of three-dimensional RNA fragments.
• 2010-: First report on the secondary structure of the HIV-2 leader RNA at the dimer level, development of the fully automated and fast method and server for prediction of high-resolution RNA 3D structures from secondary structure.

Research profile of the BIONMR group

The group’s primary focus is on understanding the structure, function and dynamics of nucleic acids, particularly RNA. We apply both biophysical and biochemical techniques, with a strong emphasis in nuclear magnetic resonance spectroscopy (NMR) which provides a method for determining the three-dimensional structures of biomolecules at atomic level and to study their dynamics in solution.

One of the major areas of  research involves structural studies of RNA quadruplexes (1,2).  In contrast to DNA, only few structural studies on RNA G-quadruplexes have been performed, and, so far, the knowledge about structural diversity or conservation of RNA G-quadruplexes has been limited. The group is particularly interested in conformational properties of RNA fragments composed of CGG, AGG and UGG trinucleotide repeats. The NMR data show that in solution these molecules fold into quadruplexes, but with entirely different topology.

Current research activity (see references 1-5)

• Structure of RNA fragments composed of CGG, AGG and UGG trinucleotide repeats.
• Conformational studies of bulged RNA duplexes.
• Structural characterization of LNA-2-’O-MeRNA/RNA and 2-’O-MeRNA/RNA duplexes.

Most important research achievements

Their results show that GCGGCGGC molecule folds into a dimer of dimers with two parallel stranded G:G:G:G tetrads and two antiparallel stranded G:C:G:C tetrads (Fig. A) both in the presence of K⁺ and Na⁺ cations. Substitution of one of guanosine residues to 8-bromoguanosine or 8-metylguanosine changes the quadruplex structure significantly. In solution, equilibrium between double- and four-stranded forms takes place. Two GC^Br/MeGGCGGC duplexes associate through the major grooves giving rise to tetramolecular structure. Quadruplexes are antiparallel (Fig. B) and are built of G:^Br/MeG:G^Br/MeG tetrads separated by two mixed G:C:G:C tetrads.

Equipment

• 700MHz Bruker NMR spectrometer with cryoprobe

•  500MHz Bruker  NMR spectrometer

• 400 MHz Bruker NMR spectrometer

Next to the NMR lab is the Poznań Supercomputing and Networking Center affiliated to the Institute of Bioorganic Chemistry of the Polish Academy of Sciences. The main goal was to develop scientific IT infrastructure in the region. Since 2001 PSNC has been actively involved in European research and development projects, especially in Fifth, Sixth and Seventh Framework Programme.

The Institute will celebrate the 25th Anniversary of the Institute of Bioorganic Chemistry, Polish Academy of Sciences during the conference “Towards a New RNA World“, 12-14 November, 2013.

Selected Publications

1. Ł. Popenda, R.W. Adamiak, Z. Gdaniec
Bulged Adenosine Influence on the RNA Duplex Conformation in Solution.
Biochemistry 47, 5059-5067 (2008).

2. Ł. Popenda, Z. Gdaniec, R.W.Adamiak
Structure and dynamics of adenosine bulged RNA duplex reveals formation of the dinucleotide platform in the C:G-A triple.
Arkivoc, Part 3, 130-144 (2009).

3. Kierzek, A.Pasternak, K.Pasternak, Z.Gdaniec, I. Yildirim, H.Turner, R. Kierzek
Contributions of Stacking, Preorganization, and Hydrogen Bonding to the Thermodynamic Stability of Duplexes between RNA and 2’-O-Methyl RNA with Locked Nucleic Acids.
Biochemistry 48, 4377-4388 (2009).

4. B. Skalski, K. Taras-Goslińska, Z. Gdaniec, S. Franzen
Photoinduced fluorescent crosslinking of 5-chloro- and 5-fluoro-4-thiouridines with thymidine.
J. Org. Chem. 75, 621–626 (2010).

5. G. Wenska, P. Filipiak, K. Taras-Goślińska, A. Sobierajska, Z. Gdaniec
Orientation-dependent quenching of the triplet excited 6-thiopurine by nucleobases
J. Photochem. Photobiol. A-Chem. 217, 55–61 (2011).