Centre for Chemical Biology ERIC

Dr. habil. Jacek Kolanowski
Head

jacek.kolanowski@ibch.poznan.pl
ext. 1165

Research activity

Centre for Chemical Biology ERIC is an academic platform with advanced research infrastructure that helps users from academia and industry identify new molecular tools and bioactive compounds and their mechanisms of action for research and/or as a starting point for product development (e.g., drugs, nutraceuticals, agrochemicals etc.). The Center consists of the Laboratory of Molecular Assays and Imaging and the Laboratory of Medicinal Chemistry. The Center is also a certified partner of the European Research Infrastructure Consortium ERIC.

Keywords:

Medicinal chemistry
Optimization of "hit to lead" molecules
Chemical synthesis
Biosynthesis, biocatalysis, semi-synthesis
Isolation and identification of products
Natural products
Cheminformatics
Ultra-high-resolution microscopy, MINFLUX, FLIM, STED
Single-molecule imaging
High-throughput screening
Molecular assay design and development
Cell Painting
Image analysis
Data analysis

Research activity

Centre for Chemical Biology ERIC offers access to infrastructure and expertise in the field of high-throughput screening, high-throughput and ultra-super-resolution microscopy, and medicinal chemistry. It is a part of POL-OPENSCREEN - the Polish Platform for Screening Infrastructure for Chemical Biology and the international EU-OPENSCREEN-ERIC consortium, which works with users around the world to identify biologically active molecules and identify their mechanisms of action. The Centre carries out its R&D work in three main areas:
Screening platform - offers access to expertise and infrastructure in the development of molecular assays and performance of high-throughput screening. With miniaturization, automation and advanced scientific and research expertise, the laboratory can test the biological activity of hundreds of thousands of compounds (e.g., within the EU-OPENSCREEN library or any user library). It offers expert support in planning and conducting screening experiments based on biochemical and cellular techniques. The screening platform is also equipped with instruments dedicated to high-throughput imaging (including multiparametric imaging, such as Cell Painting assay) and offers assistance with image data analysis.
Molecular imaging platform - is part of the NEBI project - National Center for Advanced Analysis of Biological and Biomedical Imaging. The platform primarily consists of one of the only few ultra-super-resolution microscopy systems in the world - MINFLUX located at ICHB PAN. This technology allows to perform fluorescence imaging with a resolution of less than 2 nm. Our MINFLUX system combines the highest quality super-resolution imaging technologies, i.e. STED and Minflux, along with other advanced microscopy technologies (including / FLIM or FCS). The platform offers access to expertise in the performance of experiments using the mentioned microscopy techniques, and image analysis as well as expert assistance in the planning and realization of projects.
Medicinal chemistry platform - offers access to expertise and infrastructure for medicinal chemistry research, including the optimization of bioactive compounds, so-called "hit to lead," via chemoinformatics design and chemical synthesis, semi-synthesis, biocatalysis and biosynthesis of dedicated compound libraries that are particularly difficult to synthesize via classical methods. In addition, the platform offers assistance in the selection of already existing compound libraries for bioactivity assays and automated isolation, purification and characterization of compounds derived from biological material or enzymatic reactions. The laboratory specializes in the biosynthesis of natural product analogs.

Offer:

Molecular testing and HTS screening
Ultra-super-resolution microscopy (Minflux/STED)
Medicinal chemistry
Scientific consultation, including:

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Literature analysis and studies,
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Support in project preparation
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R&D campaign planning,
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Design of experiments

Offer – Molecular testing and HTS screening

Available technologies:
Types of tests:

Biochemical tests based on:

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Absorbance (Abs) (e.g., ATPase activity)
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Fluorescence (FL) and derivatives (e.g., redox/ROS activity)
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Bioluminescence (BL) (e.g., metabolic activity)

Cellular tests (using Abs/FL/BL or Imaging):

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Based on biological target (e.g. reporter assay with Fluc, Rluc or NanoLuc luciferases)
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Phenotypic (e.g., cytotoxicity)
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Multiparametric Imaging Assays (e.g., Cell Painting assay)

Compound Libraries:

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European Chemical Biology Library (EU-OPENSCREEN - 100k and 5k compounds)
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The National Library of Chemical Compounds (KBZCh)
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Commercial libraries of bioactive compounds (e.g., LOPAC 1280 compounds, PRESTWICK 1520 compounds)
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Libraries provided by users

Types of R&D work:

Biochemical tests

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Assay development (including multiparametric assays).
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Assay miniaturization and optimization
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Assay automation

High-throughput screening

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Assay transfer and automation
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Primary screening
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Hit validation

Analysis and selection of optimal hits
Analysis of available databases
Analysis of literature data
Clustering of hits for further optimization (Follow-up: Medicinal Chemistry platform)
Development and/or validation of screening technologies
Validation of advanced testing equipment

Offer - Ultra-super-resolution microscopy (Minflux/STED):

Available technologies:

STED (Stimulation Depletion Microscopy) confocal microscopy - 2D and 3D imaging, multicolor
MINFLUX (Minimal Photon Flux) microscopy - 2D and 3D imaging, multicolor, tracking
FLIM microscopy (Fluorescence-Lifetime Imaging Microscopy)
FCS microscopy (Fluorescence Correlation Spectroscopy)

Types of R&D work:

Design of the experiment
Preparation (assistance in preparation) of samples
Conducting imaging experiments
Analysis of imaging data

Offer - Medicinal Chemistry:

Hit-to-lead compound optimization

Selection of compound libraries for bioactivity testing and structure-activity relationship (SAR) analysis independently or based on screening results

Design and optimization of structure and synthesis of bioactive molecules:

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chemoinformatics analysis
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chemical synthesis

Process automation

Bio-production

Biosynthesis, biocatalysis, semi-synthesis for compounds difficult to obtain by classical methods
Automated purification, isolation and identification of chemical compounds - from biological material or enzymatic reactions

Equipment:

Detection and analysis, including:

MINFLUX/STED ultra-super-resolution microscope (Abberior)
Opera Phenix High Content Screening confocal microscope (Perkin Elmer)
CLARIOstar Plus (BMGLabtech) and Cytation (Biotek) plate readers
Shimadzu's LCMS-8040 system

Process automation, including:

Echo acoustic dispenser (Labcyte)
Multidrop combi liquid dispenser (ThermoFisher)
Hydrospeed plate washer (Tecan)

Research projects:

Selected projects which tasks are currently carried out in the Centre:

“Screening of the OPENSCREEN Diversity and Bioactives chemical library to select redox active compounds in three reactive oxygen species assays”, user: EU-OPENSCREEN central office
“Screening of the OPENSCREEN Diversity and Bioactives chemical library to investigate the interference of test compounds with bioluminescent reporters”, user: EU-OPENSCREEN central office
Development of the staining and imaging methodology to monitor the transfer of the Dicer protein from the cytoplasm to the cell nucleus, and the development of a test enabling the assessment of the cytotoxicity mechanism of the tested compounds for the screening in cell painting – project number: OPUS 2021/41/B/NZ2/03781, user: Prof. Anna Kurzyńska-Kokorniak
Cell-based high-throughput screening for small-molecule compounds diminishing molecular markers of pathogenesis in myotonic dystrophy type 2 (DM2), dr hab. Marzena Wojciechowska

Selected projects with tasks carried out in the Centre:

„High throughput screening of small molecules binding to influenza and coronavirus vRNA” – project number: xxxxx, user: Prof. Elżbieta Kierzek, Department of RNA Structural Genomics, IBCH PAS
“ECBL-based screening of S-adenosyl-L-homocysteine hydrolase from Pseudomonas aeruginosa – towards a new class of inhibitors targeting the enzyme dynamics”- project number: xxxxx, user: Prof. Krzysztof Brzeziński, Department of Structural Biology of Prokaryotic Organisms, IBCH PAS
“Multigate: dual-analyte responsive fluorescent probes for a real time multi-parametric sensing in cellular models”– project number: HOMING POIR.04.04.00-00-441F/17-00, user: dr Jacek Kolanowski, Department of Molecular Probes and Prodrugs, IBCH PAS
”FLIM imaging of erythrocytes to investigate the impact of a potential fluorescent probe sensitive to redox reactions” – project number: xxxx, user: Prof. Marek Sikorski, Faculty of Chemistry, Adam Mickiewicz University

Strategic projects for the development of the infrastructure:

Participation of POL-OPENSCREEN consortium in an international project entitled: “European Infrastructure of Open Screening Platforms for Chemical Biology European Research Infrastructure Consortium (EU-OPENSCREEN ERIC)", 2018 - 2023, project number: funding: Ministry of Science and Higher Education (now: Ministry of Education and Science)
NEBI name - xxxx, 2021 - 2023, project number, funding: POIR – The Polish Roadmap for Research Infrastructures
"EU-OPENSCREEN-DRIVE: Ensuring long-term sustainability of excellence in chemical biology within Europe and beyond", 2019 - 2024 project number: xxxxx, funding: Horizon 2020

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