Chemical biology and high-throughput screening core facility
The IMTM High-Throughput Screening (HTS) core facility is one of the largest and a state-of-the-art screening robotic platform in academia. Our goal is to accelerate discovery and development of new potential small molecule therapeutics as well as to identify and characterize novel therapeutic/biological targets. We have over 10 years of experience in running large-scaled screening campaigns on a fully automated and flexible robotic platform (HighResBiosolutions Ltd.) Our qualified and skilled team has expertise in a liquid handling, robotic automation, variety of readout technologies and big data analytics and is ready to assist and collaborate with you to accomplish your project requirements.
- Screening assays in 384 – or 1536 – well plate format
- Biochemical assays (e.g. protein – protein and protein – nucleic acid interactions, enzyme inhibition assays, receptor – ligand binding assays)
- Cell - based assays (e.g. cell proliferation assays, reporter gene assays for mapping the most significant signaling pathways and receptors)
- Cell types: immortalized cell lines (non cancer and cancer), primary cells, stem cells, senescent cells, 3D cell cultures)
- Various detection methods (e.g. absorbance, luminescence, fluorescence, fluorescence polarization)
- High content analysis (e.g. phenotypic assays, cell painting, cell cycle analysis, DNA damage/repair activity, cytoskeleton integrity, colocalization studies)
- Compound Libraries:
IMTM: Commercial compound library (over 3.000 compounds with known activity)
IMTM: Proprietary Library (over 15.000 unique small molecules)
IMTM: DrugLike Library (a collection of 100.000 small molecules with druglike properties)
HTS Screening Workflow
The goal is to translate your benchtop test to reliable, robust, and reproducible assay suitable for HTS platform. This essential step allows to reduce the reagent costs and increase the throughput. We focus on miniaturization (transfer of the assay from tubes or 96 – well plate format to 384 – or 1536 – well plate format), optimization (concentrations of components, reagents stability, DMSO tolerance, incubation time, positive and negative controls,…) automation, and validation of your assay.
Routinely primary screening campaigns are single point assays. Only one defined concentration of the compound/molecule (10 µM) is evaluated against tested target in three interplate replicates. Based on the defined threshold the active molecules are selected.
In secondary screening (dose-response curve testing) the compound is tested over a range of concentrations (7 points, dilution factor 4) to determine the concentration that results in half maximal response (IC50 or EC50 value respectively).
Data from primary and/or secondary screens are stored and analyzed in different systems (e.g. Dotmatics software, Columbus Image Data Storage and Analysis System). Main task for our team is to select true hits, the most promising candidates. To successfully select the hit we do further assays such as orthogonal, counter – screening, selectivity and cytotoxicity assays.
Assays implemented into IMTM HTS platform
- Colorimetric MTS Assay
- ATP luminescence cell viability assay
- CYP2W1-specific cytotoxic activity
- Carbonic Anhydrases inhibition assay
- Adenosine receptors binding assay
- CaFlux assay
- C-Myc activity assay
- Live - Cell cycle analysis with FUCCI indicator
- Cell painting assay
- hAR and hGR translocation activity assay
- Mitochondrial potential measurement using TMRM staining
- In vitro tubulin polymerization assay
- Sonic Hedgehog activators/inhibitors by monitoring Smo ciliary localization
- Cytoplasm-to-nucleus translocation such as NPL4
- Tau protein aggregation inhibitors
- Alpha-synuclein aggregation inhibitors
Flexible Triple MicroStar robotic system (HighResBiosolutions Ltd.)
PerkinElmer Operetta imaging system
PerkinElmer EnVision HTS Multilabel Plate Reader
PerkinElmer microplates reader ViewLux uHTS Microplate Imager
If you have any questions or would like to discuss your genomics research needs, please don't hesitate to reach out to us. Our friendly and knowledgeable team is ready to assist you. You can contact us through the following methods:
- Phone: +420 585 632 069
- Email: email@example.com
- Location: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry and Czech Advanced Technology and Research Institute, Palacky University, Hnevotinska 5, 779 00 Olomouc, Czech Republic
We are excited to be a part of your genomics research journey and look forward to collaborating with you on groundbreaking discoveries that will shape the future of science and medicine. Let's unlock the potential of genomics together!