High-throughput screening
High-throughput screening (HTS) is essential to the drug discovery process. It consists of selecting from thousands of molecules those that could have a pharmaceutical use. To do this, large libraries of repositionable compounds are tested in a biological model with a specific therapeutic target.
With more than 15 years of expertise in the screening of relevant biological models of rare and ultra-rare diseases (immortalized cells and hIPS derivatives), the platform evaluates the feasibility, advises and guides research teams in the development of their projects, from the miniaturization of the cell assay in a microplate (96-384) to the choice of a high-throughput quantifiable biomarker.
When the cell-based assay is sufficiently robust, it performs the primary screening campaign at one or more doses in single/quadruplicates, the retests and the evaluation of the EC/IC50 on customized repositionable molecule libraries.
| AVAILABLE BIOMARKER QUANTIFICATION METHODS
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| HCS |
Quantification of membrane proteins |
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Quantification of nuclear proteins |
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Proteins translocation |
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Proteins colocalisation |
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| HTS |
Various biochemical tests (fluorescence; luminescence) |
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Proteins quantification (Alpha Screen ; Alpha LISA ; HTFR) |
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Quantification of luciferase test (Overexpression…) |
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Quantification of markers in absorbance |
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HCS : High Content Screening
In addition to this activity, the platform carries out R&D programs allowing the development of new biochemical and molecular assays as well as new cellular tools facilitating the quantification of specific biomarkers.
Team members
Johana Tournois
Platform Manager (CECS)
Johana joined I-Stem in 2006 and has been in charge of the screening platform since 2016. She is specialized in robotics, data management and miniaturization.
Amandine Thibaudeau
Platform Engineer (CECS)
Amandine joined the platform at the end of 2022 to reinforce the Screening team. Amandine has a Master in Cellular Engineering from the University of Poitiers.
Yanis Genevois
Apprentice Platform Technician (CECS)
Collaborations
ANR targetBD : Pharmacological approach to lithium-resistant bipolar disorder.
– INSERM, Centre de Recherche en Myologie, Sorbonne Université, UMRS974, INSERM, Institut de Myologie-Faculté de Médecine de la Pitié Salpêtrière, Antoine Muchir
– CNRS UMR 5310 – INSERM U1217, Institut NeuroMyoGène, Université de Lyon, Arnaud Jacquier, Laurent Shaeffer
– INSERM U955 IMRB UPEC, Créteil, Frederic Relaix
– INSERM U1251, Marseille Medical Genetics, Valérie Delague
Publications
Identification of signaling pathways modifying human dopaminergic neuron development using a pluripotent stem cell-based high-throughput screening automated system: purinergic pathways as a proof-of-principle.
01 January 2023
Frontiers in pharmacology
Contribution of Human Pluripotent Stem Cell-Based Models to Drug Discovery for Neurological Disorders.
24 November 2021
Cells
Rescuing compounds for Lesch-Nyhan disease identified using stem cell-based phenotypic screening.
27 February 2020
JCI insight
Bravo-Benchcel
Medium flow pipetting machine associated with a microplate storage station, used for the development of the first steps of the Assay development.
Biocel 1800
The Institute’s high throughput screening platform for compound management and primary screening (2006 AFM_Inserm_Genopole)
Plateforme de fixation et d’immuno-marquage
Used to perform high-throughput labeling during High Content Screening (HCS) (2018 or 2019)
Clariostar
Multi-mode HTS microplate reader allowing the quantification of markers in luminescence, fluorescence, TR-FRET, Alphascreen, Alphalisa, HTRF and Absorbance. (2013 genopole)
CX7 Cellomics et Image Express (Lecteurs HCS)
Automated microscope for fluorescence quantification of biomarkers by immunofluorescence with objectives ranging from 5X to 63X.
Quantstudio 12k et 7k
Real-time PCR equipment to quantify the expression of target genes in 96 or 384 wells (NGS platform)