High capacity and combinatorial screening to find biologically-active molecules and optimize their mixtures for maximal efficiency and synergy identification (e.g. on human and plant cell lines, as well as iPS)

The AGAMEDE^TM Intelligent Screening System is a unique and innovative integrated software and infrastructure platform for high throughput and combinatorial screening. Within this transnational access call, IBCH-PAS offers a High Throughput screen on more complex biological models like human iPS or plant cell lines and a subsequent unique follow up combinatorial screen to optimize a mixture of up to 24 hit compounds identified in the first HTS screen to maximize biological effect and look for synergistic responses. IBCH-PAS does this by performing assays in 96 and 384 well plates with quantification of absorbance, fluorescence or luminescence, for example (but not limited to) to assess cell viability or monitor gene expression.

The Institute of Bioorganic Chemistry, Polish Academy of Sciences (IBCH PAS), established in 1988, conducts cutting-edge, interdisciplinary research in bioorganic chemistry, molecular, systems and synthetic biology, as well as bioinformatics.

The Centre for High Throughput Screening Studies incorporates an HTS-IBCH laboratory, established in 2015, and brings together over 25 members of various interests and skills i.e. biologists, chemists, automation specialists, engineers and programmers. This group created a unique and innovative software and instrumental infrastructure for high capacity and specialist screening as well as assay development and target identification. The HTS-IBCH Laboratory at the Centre for High Throughput Screening develops an AGAMEDE^TM Intelligent Screening System that is able to work in a high throughput and/or an iterative mode for automatic and efficient solving of biological problems.

The current screening capacities include in particular

• High Throughput Screening of libraries of chemical compounds, ligands, nucleic acids, peptides, etc., in a closed loop with modelling of complex biological systems, in order to propose new compounds pharmacologically active against specific disease entities, develop mixtures of active compounds with desired properties, etc.
• Multi-parametric screens for more reliable and insightful identification of biologically-active compounds with simultaneous insight into the mechanism of their action already at the stage ofthe first screen.
• Chemo-sensitivity and chemo-toxicity tests for finding tailored cocktails of anticancer drugs/ agents (developing a personalized anticancer therapy).
• Combinatorial screenings for optimization of mixtures of compounds to maximize biological effects, like for example:
  • Finding and optimization of chemical solutions, cell media, buffers, etc. for different purposes (e.g. cell differentiation potency, crystallization purposes),
  • Optimization of bioprocess conditions (e.g. production of therapeutic monoclonal antibodies or chemotherapeutic agents in bioreactors),
  • Modelling of evolutionary processes, for better understanding and verification of evolutionary theories, concepts and hypotheses,
  • Finding optimal conditions for self-replicating systems.

Within this call, IBCH-PAS offers a High Throughput Screening on more complex and unusual biological models like human iPS or plant cell lines (grown in suspension), based on the assays in 96 and 384 well plates with quantification of absorbance, fluorescence or luminescence, or High-Content Fluorescent Imaging. Example assays might include cell viability or monitoring a level of gene expression (e.g. for medicine and/or biotechnology) as well as High Content Fluorescent Imaging. In addition, as a part of the access, we also offer a follow-up combinatorial screen including up to 24 hit compounds identified from the HTS campaign, in order to optimize their composition for maximal biological effect.

Number of compounds screened

100,000 (full commercial set) of the EU-OPENSCREEN ERIC compound library

Time frame for screen up to validated hits

9 months (the time may vary depending on the development stage of the screen and the complexity in the execution)

The HTS-IBCH Laboratory equipment to support this work includes e.g. the 6-axis Mitsubishi robot with a 1.5 meter arm for plate transfer, a liquid handling workstation with 96 and 384-heads (Agilent Bravo), an acoustic dispenser, 4 liquid microdispensers (Formulatrix Tempest), an imaging plate reader (BiotekCytation 3) as well as a dedicated high throughput plate reader and a separated state-of-the-art multidetector high throughput confocal microscope for High Content Analysis, an automated incubator (Thermo Cytomat 6001-C4), 10 automated plant chambers (Phytotronix), supporting equipment (e.g. plate labeller (Agilent vCode), a plate centrifuge (Agilent vSpin), plate sealer (Agilent PlateLoc), plate piercer (Agilent Piercer) and plate stackers (3 Agilent vStacks, 2 Agilent BenchCel, 1 Thermo Carousel)).

• Maintenance and proliferation of the user’s cell culture.
• Validation of the assay/reporter cells provided by the user to ensure robustness in HTS format.
• Miniaturization of the assay into 96 and 384-well formats.
• Pilot screen using 5,000 compounds from the EU-OS compound library.
• Analysis of pilot screen data.
• Full screen with the remaining 95,000 compounds of the EU-OS compound library • Data analysis and subsequent selection of primary hits.
• Hit picking of primary hits for hit validation.
• Hit validation (rescreening of up to 1,000 selected hits).
• Combinatorial hit screening (up to 24 selected hits mixed together; usually 5 cycles and 3840 various formulations per one cycle) All services are carried out through the Centre for Hight Throughput Screening Studies and via access to AGAMEDE^TM Intelligent Screening System.

Please note that this project includes the possibility of re-screening during potential chemical optimization under the medicinal chemistry call starting in 2021 (tentative date).

The prerequisite starting point to qualify for access is the availability of an established bioassay with an absorbance, fluorescent or bioluminescent readout, a reporter cell line (if needed) and associated key bespoke reagents, media and consumables, developed at lab-scale by the successful applicant.

The assay format is compatible with the performance in microtiter plates allowing the quantitative determination of an optical parameter (e.g. absorbance, fluorescence, luminescence) or High Content Imaging. The target of the assay is determined by applicant’s bioassay.

As specifics of the assay transfer procedure may vary between partner sites, the applicant and the individual sites will agree on the appropriate steps and logistics together.

Apply now

Topics / Keywords:

drug discovery, small molecules, high-throughput screening, cell-based assays

Open Time:

Start date:
June-01-2019 (20:00 CET)

Closing date:
September-30-2019 (20:00 CET)

Contacts:

Scientific / technical / machine / methods contact: jacek.kolanowski@ibch.poznan.pl, Radosław Pilarski, rapil@ibch.poznan.pl