Instytut Biochemii i Biofizyki PAN (IBB PAN)
Institute of Biochemistry and Biophysics Polish Academy of Sciences (IBB PAS), established in Warsaw in 1957, has state-of-the art laboratories for highly specialized studies in the ields of molecular biology of plants, fungi, and microorganisms, biophysics and proteomics as well as computer modeling and bioinformatics.
Institute of Biochemistry and Biophysics PAS generated several therapeutic technologies developed from fundamental research carried out in its laboratories. These technologies are based on novel mechanisms of pharmacological intervention, such as – natural miRNA molecules, peptidomimetics, vaccines or small-molecule protein correctors, and therefore belong to the highest class of innovative medical solutions. The described solutions may contribute to the development of new drugs for the diseases, which either have no effective therapy currently or the available therapeutics are insufficient and/or carry significant adverse effects. At the moment, activities
of the Institute of Biochemistry and Biophysics PAS are focused on the improvement of developed therapeutic molecules in the treatment of autoimmune diseases, various conditions related to the inflammatory processes, resistance to antibiotics, influenza virus infections and cystic ibrosis.
The modern and sophisticated research equipment including hi-tech core facilities, and the top-caliber scientific expertise of its research staff members enable the Institute to advance and explore various fields of biology, medicine and pharmacology, agro-food industry and biotechnology, with ultimate goals focused on fundamental research as well as human and animal health and wellbeing.
The Institute is involved in over 130 national and international research projects funded both locally and by EU. IBB PAS is a member of one of the largest infrastructural scientific projects in Poland: the “Center for Preclinical and Technological Research” CEPT, as well as a member of the “Biocentrum Ochota” consortium in Warsaw. IBB PAS has three projects included on the list of the Polish Roadmap for Research Infrastructures – “ELIXIR – a system for recognition of complex biological systems” (leader), PolarPOL.Polish Multidisciplinary Laboratory for Polar Research (partner) and POL-OPENSCREEN (partner & partner site in EU-OPENSCREEN).
In POL-OPENSCREEN, IBB is building the
Platform for in silico screening, ADME and lead compound structure optimization
Our group uses a wide range of bioinformatics approaches and develops its own unique tools to solve various biological problems and propose novel therapeutic molecules.
Several of our projects have been already confirmed experimentally.
Small molecule discoveries with emphasis on protein-protein interaction inhibitors, including epigenetic modifiers, drugs against basic defect of cystic fibrosis, exosome and mTOR/PI3K modulators.
We have proposed several therapeutic technologies based on novel pharmacological molecules, such as:
1. Natural miRNAs – specific plant-derived miRNAs are used to interact with mRNA coding protein FAN (Factor Associated with Neutral Sphingomyelinase Activation) and thus negatively regulate its expression. By this means plant-derived molecules decrease organism inflammatory responses – reduces level of pro-inflammatory proteins (e.g. CXCL2, IL-6) and proliferation/recruitment of leukocyte population. Presented molecule may be used to treat known autoimmune diseases and/or various conditions related to the inflammatory processes.
2. Inhibitors of protein-protein interactions correcting the basic defect of ∆F508-CFTR in cystic fibrosis. We applied molecular modeling methods to propose a unique mechanism of pharmacological intervention and to discover four new drug-like compounds, which have been proven by series of experimental studies (including human bronchial primary epithelial cells derived from CF patients (CF‐HBE) as well as in vivo analysis on CF animal model – ∆F508/∆F508 mice). Identified molecules are of a great potential to become good candidates for future drug(s) against basic defect causing CF.
3. We developed a novel screening procedures which allow a sufficient degree of flexibility for the analysis of a large database of compounds. This methodology was applied to find the first non-nucleotide DNA methylation inhibitors. Two of them have been tested experimentally and proven to be efficient especially against common cancer types such as leukemia and colon cancer. One of the compounds, RG-108 is commonly used today. The developed solutions may provide alternative therapeutics for human diseases for which there are no effective drugs or the available ones are insufficient, very expensive and/or carry numerous of side effects.
Possible services offered under POL-OPENSCREEN and EU-OPENSCREEN ERIC include the following elements:
1) NEST computing cluster based on Intel and AMD processors, professional graphic computing cards and programmable coprocessor cards. In 2010, the NEST cluster was ranked 86th in the ranking of the fastest supercomputers TOP500.
2) Unique large-scale in silico screening system, based on proprietary molecular fitting solutions and machine learning based assessments. The system enables long-term (nanosecond) simulations of molecular dynamics, energy minimization in force fields, and quick and sensitive searches of the chemical space of low-molecular compounds based on 3D structures, physicochemical features and their combinations (pharmacophores).
3) Service for analyzing data from large-scale DiSCuS experiments. The website has been designed to facilitate cooperation between medical chemists, a screening laboratory and bioinformatics, including thanks to support for any format and automatic normalization of various data types. The website offers a number of tools for the analysis and visualization of the results of screening experiments, both experimental and in silico.
4) Service of designing peptide inhibitors and peptidomimetics, service of designing miRNA as modulators of metabolism. Systems biology tools, incl. reactome analysis and FBA / FVA,
5) Rich equipment and methodological facilities and highly qualified staff successfully using advanced experimental techniques belonging to ADME