Laboratories

Research

Main Scientific Achievements

• We established the general methodology for the construction of protein-protein interaction peptide inhibitors and successfully applied it to a number of biologically meaningful examples.
• We discovered novel potent deltaF508-CFTR correctors as potential drugs against Cystic Fibrosis (CF)
• We proposed a comprehensive, genome-wide model of translation.
• We described the role of plant miRNAs in the antiinflammatory properties of selected edible plants.

Research Description

Scientific interests of our laboratory include, but are not limited to:

• Protein-protein recognition and the design of protein-protein interaction inhibitors.
• Macromolecular crowding.
• Modeling and modifying the regulation of basic cellular processes and metabolic pathways.
• Protein modeling.
• Analyses of genome sequence data (particularly in the context of phylogenetic analysis).
• Development of drug design methodologies.
• Analyses of protein interaction networks.
• Literature mining.

Methodology

In our laboratory, we use software tools for:

• Sequence and structure analysis (e.g., EMBOSS).
• Visualization and structure modeling (e.g., Chimera, YASARA, Swiss-PDBViewer).
• Pathway and metabolic pathway modeling and analysis (e.g., Cytoscape, IPA, Gepasi)
• Docking (e.g., DOCK).
• Molecular dynamics (e.g., AMBER, GROMACS).
• Home-developed tools (e.g., kalasanty, pafnucye, plec, oddt, transimulation, ht-sas, elise, tools4mirs).

Our HPC infrastructure is built around HP blade servers with Intel Xeon X5650 6-core processors and AMD Opteron 6174 12-core processors. Each core has 2 MB of RAM. The servers are diskless and connected with a high speed (32 Mb/s) InfiniBand QDR40 connection. This interconnect provides direct memory access and enables ultra-low latency between computing nodes. The infrastructure consists of 32 Intel-based servers and 16 AMD servers, for a total of 1152 cores. This environment is further enriched by 8 GPU Nvidia TESLA C2080 cards with 448 cores each. Storage is built around LustreFS, a special-purpose modular system that is designed for high I/O memory (6 rack servers, 72 Intel cores) and a HITACHI AMS2500 storage system with 0.5 PB of storage size. Additionally, five application servers provide virtualization capacities, with a total of 240 cores and 1 TB of RAM installed). Software that is used in this installation is almost exclusively free and open source stack (Linux, Torque, Maui, Xen, MySQL, Apache, and others). Altogether, our HPC environment is able to achieve over 40 Tflops.

Selected Publications

• Discovery of novel potent ΔF508-CFTR correctors that target the nucleotide binding domain. Odolczyk N, Fritsch J, Norez C, Servel N, da Cunha MF, Bitam S, Kupniewska A, Wiszniewski L, Colas J, Tarnowski K, Tondelier D, Roldan A, Saussereau EL, Melin-Heschel P, Wieczorek G, Lukacs GL, Dadlez M, Faure G, Herrmann H, Ollero M, Becq F, Zielenkiewicz P, Edelman A. EMBO Mol Med. 2013 Oct;5(10):1484-501. doi: 10.1002/emmm.201302699.
• A comprehensive, quantitative, and genome-wide model of translation. Siwiak M, Zielenkiewicz P. PLoS Comput Biol. 2010 Jul 29;6(7):e1000865. doi: 10.1371/journal.pcbi.1000865.
• Mapping Protein-Protein Interactions of the Resistance-Related Bacterial Zeta Toxin-Epsilon Antitoxin Complex (ε₂ζ₂) with High Affinity Peptide Ligands Using Fluorescence Polarization. Fernández-Bachiller MI, Brzozowska I, Odolczyk N, Zielenkiewicz U, Zielenkiewicz P, Rademann J. Toxins (Basel). 2016 Jul 16;8(7):222. doi: 10.3390/toxins8070222.

Collaborations

• Joerg Rademann, Freie Universitaet Berlin, D
• Aleksander Edelman, INSERM, FR
• Sarah Reece, Edinburgh University, UK
• Chris Janse, Leiden University, NL
• Wolfram Saenger, Freie Universitaet Berlin, D
• Grażyna Faure-Kuźmińska, Institute Pasteur, Paris, France
• Stephanie Trudel, Universitaire Amiens Picardie, Amiens, France