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Instrument & Lab Support (ILS) group, in conjunction with the Screening Discovery Platform (SDP) group employs dynamic robotic platforms for high-throughput screening of chemical libraries and RNAi collections. Our fully-automated robotic platforms are located in BSL-2+ (moderate infectious) and BSL-3 (highly infectious) laboratories suitable for most pathogens and biological research. We are capable of screening assays covering a wide range of detection technologies including fluorescent, bioluminescence, absorbance, and imaging. Screening has the potential to uncover new leads for development into biomarkers, probes, and drugs. For additional information, please contact Research Technology Management Team (031-8018-8032 | RTV-DIV@ip-korea.org)
Assay Development & Screening Capabilities
Visual– and cell-based high throughput screening employing a target-free approach to identify novel drug candidates
Developed at the Institut Pasteur Korea, PhenomicScreen™ is a visual– and cell-based high throughput/ high content target-free screening platform. It quantifies biological events in living cells and allows the cells themselves to identify the most effective drug targets from millions of complex molecular interactions.
Disease mechanisms addressed by the identified compounds are likely to be physiologically relevant, since compounds are tested and studied in cells. Thus, potency, cytotoxicity, membrane permeability and intracellular safety are all tested at the earliest stage of the drug discovery process, thereby eliminating toxic compounds and identifying the most promising candidates for further investigation.
Chemical libraries for screening
Chemical screening can be used to identify molecules with biological activity from our libraries covering 400,000 compounds including synthetics and natural products. The collection was assembled with the help of our internal Cheminformatics and Chemistry Platform groups, as well as established strategic partners.
Some of the strategic suppliers are: ChemBridge, ChemDiv, Enamine, MicroSource, NIH Diversity Set, Prestwick, Tocris, SelleckChem, SigmaAldrich and NCI Natural Products Repository.
Functional genomics approach used to identify therapeutic targets
PhenomicID™ works by assessing the impact of genes in the cell by turning off each gene, one by one. The entire human genome and focused gene sets are available for screening using cell imaging technology to identify physiologically-relevant molecular pathways and targets involved in the development of the phenotype of the diseases under study.
Gene silencing utilizes RNAi as sequence specific nucleotides to target mRNA for translation repression or degradation. Libraries in the form of short interfering RNA (siRNA) and short hairpin RNA (shRNA) are used to interrogate the cellular system of interest to identify previously unknown target genes associated with diseases, and to find new targets that can serve as a focus for innovative drug discovery. We provide a complete pipeline for genome-wide or focused screening including assay optimization, high-throughput / high-content screening, analysis, and bioinformatics.
Gene involved in signaling pathway is tagged with green fluorescence marker and effective silencing by RNAi leads to phenotypic change from cytoplasmic to nuclear localization
Target of interest is silenced with RNAi leading to identification of cofactors involved in its expression by change in green fluorescence.
RNAi collections for screening
RNAi technology enables sequence specific knockdown of genes to identify new targets and cell signaling pathways for drug discovery. Our RNAi collections for large scale screening covers both siRNA and shRNA technologies as follows:
- Human genome-wide library with coverage of ~22,000 genes with 3 siRNA targeting each gene in 384-well arrayed format
- Human kinase focused library covering ~700 genes with 3 siRNA targeting each gene in 384-well arrayed format
- Human phosphatase focused library covering ~300 genes with 3 siRNA targeting each gene in 384-well arrayed format
- Human genome-wide library coverage of ~16,000 genes with 5 shRNA targeting each gene in 384-well arrayed format
Target-Free Structure-Activity Relationships (SAR)
Innovative approach to develop hits into lead compounds
Target-free SAR improves the efficiency of turning hit compounds into lead compounds by leveraging the information obtained through a variety of cellular structure-activity-relationships studies. Chemists, chemoinformaticians and pharmacologiests at Institut Pasteur Korea use the approach to analyze and tweak validated hit compounds with the aim of modifying the scaffolds to improve properties such as solubility, stability, activity, and tolerability. This approach minimizes the trial-and-error that might occur at later stages of drug discovery and accelerates the research process by concurrently measuring the pharmacological properties that contribute to lead optimization.
Automation Management Solutions
Institut Pasteur Korea(IPK) is equipped with several robotic platforms and standalone instruments that are some of the essential tools needed to perform drug screening. IPK is one of the unique in offering automated systems in BSL2+ and BSL3 laboratory conditions, thus allowing us to offer exclusive screening conditions and enabling us to screen for MERS, TB, HBV, Ebola to name a few.
Sample Management Tools
The compound and RNAi libraries preparation is performed using several automated liquid handling tools, which are used for low volume transfer (0.250uL to 5ul) for assay plates preparation and midrange transfer (10uL to 100uL) for library reformatting.
HummingWell – CyBi
Personal Pipettor – Apricot Designs
Assay Optimization Tools
IPK is equipped with several Multilabel readers that are used for exploratory biology, assay development and screening projects. These include the Perkin Elmer EnVision, Perkin Elmer VICTOR3™ V & Stacker Multilabel Readers and a Molecular Devices SpectraMax® M5 Multilabel readers are used for Fluorescence Intensity (FI), Fluorescence Polarization (FP), Time-Resolved Fluorescence (TRF), Absorbance (Abs) and Luminescence (Lumi) technologies.
Perkin Elmer EnVision
Perkin Elmer VICTOR3™ V & Stacker Multilabel Readers
Molecular Devices SpectraMax®M5
HTS Automated Platforms
The High throughput screening automated robotic platforms are fully capable of running full scale screening in either BSL 2 or BSL 3 laboratory conditions. The robotic platforms are used to limit our scientist’s exposure to those environments as well as perform the work efficiently 24hrs / 7 days a week.
In BSL-3 we have a Perkin Elmer OPERETTA™ high content imaging system with a 28 microtiter plate capacity individual stacker driven by a Perkin Elmer robotic arm with barcode scanning capability, keeping track of each plate.
In BSL-2 laboratories we have two automated platforms that sustain our screening campaigns. A Perkin Elmer OPERETTA™ high content imaging system with a 28 microtiter plate capacity stacker driven by a ThermoFisher robotic arm with barcode scanner for plates tracking.
A Cell Explorer™ platform incorporating a confocal Perkin Elmer OPERA microscope and Perkin Elmer EnVision Multilabel reader with a Perkin Elmer JANUS™ and BioTek Elx405 washer for cell fixing and media swap. In addition, we use an Agilent VSpin™ centrifuge and a Liconic incubator with a 44 microtiter plate capacity.
R&D Major Research Facilities