High-throughput Screening platform. U1177 includes a screening facility set up at the Pasteur Institute in Lille and operated by six biologists (2 engineers, 1 assistant professor, 1 post-doctoral research fellow and 2 assistant engineers). Its mission spans the whole medicinal chemistry support process: compound library management, assay development, screening to hit generation and the hit-to-lead process. Key workstations are liquid handling systems (CyBI™-Well, Biomek® NX), automated multi-mode fluorescence/ luminescence readers (Mithras LB940 Research III, Victor™3V), a lightcycler 480 and a cell culture unit. Since 2008, this facility was recognized as an IBiSA platform.
High-Content Screening plaform. U1177 is part of the HCS Equipex ImagInEx BioMed. www.bicel.org
Chemical Library. The laboratory has assembled a library of 70.000 compounds formatted for screening in 96-well plates (SBS standards). Compounds have been selected from commercial vendors or prepared by our chemists using state-of-the-art selection and design criteria, in terms of diversity and “drug / lead-likeness”. The sample management system avoids repeated freeze thaw cycles and ensures the longest possible lifetime for all the samples. Sample tracking is seamless throughout the sample’s life (from ordering to testing). To manage compounds and associated results, a LIMS system has been implemented in the Unit using Access / Isis databases and pipeline pilot™ (a high-throughput data analysis and mining system for drug discovery informatics).
Assay Development and Compound Screening. The laboratory has a recognized expertise in the development of miniaturized, fast and robust assays for medium to high throughput screening. All critical screening parameter are optimized in terms of reagent cost, required manpower and time, as well as its discriminating power, as measured by the Z’ and eventually the Z factor. We develop homogenous assays, highly convenient to perform high throughput screening, as well as ELISA, LCMS assays or cell-based assays (reporter gene, BRET…) to study enzymatic reactions, protein-protein interactions, DNA-protein interaction, GPCR….Thermal shift assays are also used to measure protein-ligand interactions. Assay development and screening campaigns are realized using good laboratory practices to ensure the traceability and the quality of the data. We collaborate with national and international biological research teams that provide us target proteins or activity tests to be optimized for HTS : Pr Wei-jen Tang (University of Chicago), Pr H. Nagase (Imperial College, Londres), Pr Joost Schymkowitz (VIB Switch lab., Brussel), Pr B. Staels (U1011, Institut Pasteur Lille), Dr Serge Bénichou (U567, Institut Cochin, Paris), Dr Robin Fahraeus (U716, Hôpital St Louis, Paris), Dr Alain Baulard (U629, Institut Pasteur Lille), Dr Nathalie Bonnefoy (U851, Université Lyon 1)…
The platform is part of the national consortium GDR # 3056 « ChemBioScreen », www.chembioscreen.fr
Ce Groupement De Recherche regroupe les équipes académiques française impliquées dans les approches de « chemical biology » et un ensemble de plateformes de criblage.
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Mathieu, A. L., Sperandio, O., Pottiez, V., Balzarin, S., Herledan, A., Elkaim, J. O., Fogeron, M. L., Piveteau, C., Dassonneville, S., Deprez, B., Villoutreix, B. O., Bonnefoy, N., & Leroux, F. Identification of Small Inhibitory Molecules Targeting the Bfl-1 Anti-Apoptotic Protein That Alleviates Resistance to ABT-737. J Biomol Screen,2014 19(7): 1035-1046 10.1177/1087057114534070
Couturier, C., & Deprez, B. Setting up a Bioluminescence Resonance Energy Transfer high throughput screening assay to search for protein/protein interaction inhibitors in mammalian cells. Frontiers in Endocrinology,2013, 3: 100.10.3389/fendo.2012.00100
Andres, M. Best Poster Prize. New insights into a potential therapeutic target regulating Unfolded Protein Response and subsequent inflammation in liver and muscle. Drug Discovery Day, Lille, France 2019