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Department of ​RNA Structural Research

dr hab. Miłosz Ruszkowski

Dr. hab. Agnieszka Kiliszek, prof. IBCH PAS

Head of Department

kiliszek@ibch.poznan.pl
ext. 1278

Researchers:

prof. dr hab. Wojciech Rypniewski
profesor instytutu

Technical Staff:

mgr Martyna Mateja-Pluta
specjalista chemik

dr Katarzyna Biniek-Antosiak
chemik

PhD students:

mgr ​Faizan Faizan
doktorant

mgr ​Bogna Pinkiewicz
doktorant

mgr ​Aleksandra Sokołowska
doktorant

Na zdjęciu znajdują się osoby pracujące w Zakładzie Badań Strukturalnych RNA

Research activity

Research area
  • Structural studies of RNA molecules related to human physiology and medicine using crystallographic, microED and cryoEM methods
  • Structural analysis of RNA molecules associated with neurodegenerative diseases (e.g., ALS/FTD) caused by abnormal expansion of repetitive sequences and investigations of toxic interactom between RNA and protein molecules (collaboration with prof. Boris Rogelj, Jožef Stefan Institute in Ljubljana, Słowenia)
  • Rational design of small molecules based on crystal structures of RNA-ligand complexes (collaboration with Prof. Kazuhiko Nakatani, Osaka University, Japan; collaboration with Prof. Elżbieta Kierzek ICHB, PAN)
  • Crystallographic analysis of RNA complexes with antisense oligonucleotides (e.g., PNA); collaboration with OliPass, Republic of South Korea
  • Development of a method to stabilize RNA hairpin structures under crystallization conditions
  • Synthesis of nucleotide and non-nucleotide RNA linkers
  • Determination of the effect of modifications on the tertiary structure of RNA (collaboration with Prof. Ryszard Kierzek, IchB, PAS).
  • Thermodynamic and structural analysis of native and modified RNA molecules, RNA-ligand complexes using DSC (differential thermal calorimetry), UV melting, CD (circular dichroism) in regards to crystallographic models
  • Crystallographic analysis of proteins
Keywords
  • RNA crystallography
  • Neurodegenerative diseases caused by expansion of repetitive sequences
  • RNA cryoEM
  • RNA microED
  • RNA-ligand complexes
  • RNA-protein complexes  
  • stability of RNA hairpin structures
  • UV melting of RNA molecules
  • differential scanning calorimetry (DSC)
The figure shows a crystal structure of RNA containing CAG repeats associated with the pathogenesis of certain neurodegenerative diseases. On the left is a crystal model of an RNA complex with a small CMBL molecule. Two ligand molecules are bound to the center of the helix. It can also be seen that on each strand of the duplex, two residues, guanosine and cytosine, are pushed out of the helix. In the center of the figure is a schematic representation of the crystal structure of the complex shown on the left. The diagram shows the secondary structure of the duplex. Each ligand molecule interacts with two adenosine residues located on opposite strands. The right side of the figure shows the detailed interaction of an adenosine residue with the CMBL ligand. The adenosine interacts with the Watson-Crick edge through two hydrogen bonds with the naphthyridine ring of the ligand, forming a pseudo-canonical adenosine-CMBL pair.
The figure shows the crystal structure of an RNA model with the sequence G2C4 interacting with a small molecule of the ligand ANP77. In the center, in the circle, is a three-dimensional model RNA consisting of four strands forming a triplex structure with two overhanging cytosine residues at each end of the molecule. A ligand is bound to one of these. The detailed interactions between the cytosine residues and the ligand are shown on the right. The ligand consists of two naphthyridine units connected by a short linker. The nitrogen functions of the naphthyridines are involved in forming hydrogen interactions with the two cytosine residues. The ligand and the cytosines form two pseudocanonical Watson-Crick pairs. On the left is a model in which multiplexed hexanucleotide repeats of G2C4 form a triplex structure. The model was generated based on the presented crystallographic studies.
The figure shows two crystal models of a duplex containing a UGG motif. On the left is the structure of the RNA helix crystallized in the absence of divalent cations. On the right is the RNA helix crystallized in the presence of Ba2+ ions. The figure shows that the two ions are adjacent to each other in the major groove of the RNA helix. This causes the narrowing of the groove compared to the helix without ions, shown on the left. This structural change is marked by a double-headed line.

Research Projects

  • A comprehensive structural and functional analysis of toxic RNA-protein interactions for better understanding and therapeutic targeting of amyotrophic lateral sclerosis and frontotemporal dementia. NCN grant OPUS-28 (LAP): 2024/55/I/NZ5/02887, PI: dr hab. Agnieszka Kiliszek
  • Crystallographic analysis of RNA-ligand complexes. Towards rational design of lead compounds for development of therapies against neurodegenerative disorders. NCN grant: 2022/45/B/NZ7/03543, PI: dr hab. Agnieszka Kiliszek
  • Enzymes of the L-methionine biosynthetic pathway as novel molecular targets for antifungal chemotherapy. NCN grant: 2020/39/B/NZ7/01519, PI: Prof. Wojciech Rypniewski
  • Development of methodology for stabilisation of RNA hairpins for crystallographic study. NCN grant: 2017/26/E/NZ1/00950, PI: dr hab. Agnieszka Kiliszek
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