Screening Sciences

Team

  • Team Leader: Florence Leroux PhD
  • Cyril Couturier PhD - Assistant Pr
  • Julie Dumont - Study engineer
  • Adrien Herledan- Study engineer
  • Sandrine Dassonneville - Assistant engineer
  • Valerie Landry -  Study manager

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.

Publications

Herledan, A., Andres, M., Lejeune-Dodge, A., Leroux, F., Biela, A., Piveteau, C., Warenghem, S., Couturier, C., Deprez, B., & Deprez-Poulain, R. Drug Target Engagement Using Coupled Cellular Thermal Shift Assay—Acoustic Reverse-Phase Protein Array. SLAS DISCOVERY: Advancing Life Sciences R&D,2020, 25(2): 207–214.10.1177/2472555219897256

Leroux, F., Bosc, D., Beghyn, T., Hermant, P., Warenghem, S., Landry, V., Pottiez, V., Guillaume, V., Charton, J., Herledan, A., Urata, S., Liang, W., Sheng, L., Tang, W.-J., Deprez, B., & Deprez-Poulain, R. Identification of ebselen as a potent inhibitor of insulin degrading enzyme by a drug repurposing screening. Eur. J. Med. Chem.,2019, 179: 557-566.10.1016/j.ejmech.2019.06.057

Colin, B., Deprez, B., & Couturier, C. High-throughput DNA plasmid transfection using acoustic droplet ejection technology. SLAS Discovery,2019, 24(4): 492-500.10.1177/2472555218803064

Colin, B., Rocq, N., Deprez, B., & Couturier, C. High-Throughput DNA Plasmid Multiplexing and Transfection Using Acoustic Nanodispensing Technology. J. Vis. Exp.,2019, e59570: in press

Chapuis, J., Flaig, A., Grenier-Boley, B., Eysert, F., Pottiez, V., Deloison, G., Vandeputte, A., Ayral, A.-M., Mendes, T., Desai, S., Goate, A. M., Kauwe, J. S. K., Leroux, F., Herledan, A., Demiautte, F., Bauer, C., Checler, F., Petersen, R. C., Blennow, K., Zetterberg, H., Minthon, L., Van Deerlin, V. M., Lee, V. M.-Y., Shaw, L. M., Trojanowski, J. Q., Albert, M., Moghekar, A., O’Brien, R., Peskind, E. R., Malmanche, N., Schellenberg, G. D., Dourlen, P., Song, O.-R., Cruchaga, C., Amouyel, P., Deprez, B., Brodin, P., & Lambert, J.-C. Genome-wide, high-content siRNA screening identifies the Alzheimer’s genetic risk factor FERMT2 as a major modulator of APP metabolism. Acta Neuropathologica,2016. doi:1-12.10.1007/s00401-016-1652-z

Bosc, D., Jakhlal, J., Deprez, B., & Deprez-Poulain, R. Kinetic target-guided synthesis in drug discovery and chemical biology: a comprehensive facts and figures survey. Future Medicinal Chemistry,2016: in press. doi:10.4155/fmc-2015-0007 OPEN ACCESS

 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

Personal Communications

  • Lesire, L. Imaging and quantifying aggresome in an automated miniaturized microscopy assay.,Drug Discovery Day,Lille, France,18th jan. 2019
  • Lesire, L. Visualisation and quantification of cell aggresome in an automated miniaturized assay 2e Journée de la Recherche de la Faculté de Pharmacie,Lille, France,11th Jul 2018 flash.
  • Henninot, A., Deprez, B., Urbain, R., Fontayne, A., & Beghyn, T. LCMS: a tool for pharmacologic screening.,XXIst Young Research Fellow Meeting of the SCT,Montpellier, France,24th-25th 2014.

Poster

  • Andres, M., Hennuyer, N., Van Endert, P., Enee, E., Staels, B., Deprez, B., Lancel, S., & Deprez-Poulain, R. New insights into a potential therapeutic target regulating Unfolded Protein Response and subsequent inflammation in liver and muscle Drug Discovery Day, Lille, France, 18th Jan.,2019.
  • Lesire, L., Cruz de Casas, P., Rousseau, F., Dumont, J., Brodin, P., Deprez, B., & Leroux, F. Imaging and quantifying aggresome in an automated miniaturized microscopy assay. Drug Discovery Day, Lille, France, 18th jan.,2019.
  • Andres, M., Hennuyer, N., Van Endert, P., Enee, E., Staels, B., Deprez, B., Lancel, S., & Deprez-Poulain, R. New insights into a potential therapeutic target regulating Unfolded Protein Response and subsequent inflammation in liver and muscle 26th SCT Young Research Fellow Meeting Paris, France, 20th-22nd Feb,2019.
  • Lesire, L., Cruz de Casas, P., Rousseau, F., Dumont, J., Brodin, P., Deprez, B., & Leroux, F. Imaging and quantifying aggresome in an automated miniaturized microscopy assay. 26th SCT young research Fellow Meeting, Paris, France, 20th-22nd Feb.,2019.
  • Colin, B., Charton, J., & Couturier, C. Validation of a high sensitivity reporter system 25th SCT Young Research Fellow Meeting Orleans, France, 5th-7th March,2018.
  • Andres, M., Hennuyer, N., van Endert, P., Staels, B., Benoit, D., Lancel, S., & Deprez-Poulain, R. New insights into a potential therapeutic target regulating Unfolded Protein Response and subsequent inflammation in liver and muscle Workshop  "Endoplasmic Reticulum function in health and disease", Lucca, Italia, 21st-25th Oct.,2018.
  • Lesire, L., Rousseau, F., Dumont, J., Benoit, D., & Florence, L. Visualization and quantification of cell aggresome in an automated miniaturized assay Worshop "Cancer and Metabolism", Cambridge, UK, 25th-27th Jun,2018.
  • Lesire, L., Rousseau, F., Dumont, J., P., B., Benoit, D., & Florence, L. Imaging and quantifying ERAD pathways in an automated miniaturized microscopy assay Workshop "Endoplasmic reticulum function in health and disease", Lucca, Italia, 21st-25th Oct.,2018.
  • Lesire, L., Rousseau, F., Dumont, J., P., B., Benoit, D., & Florence, L. Visualization and quantification of cell aggresome in an automated miniaturized assay 2eme Journée de la Recherche, School of Pharmacy, Lille, France, 11th Jul.,2018.

Prizes and awards

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

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