BioPhenics - Automated Imaging Platform for High Content Screening & Phenotyping Fingerprinting
The BioPhenics Cell-Based High-Content Screening (HCS) facility specializes in chemical biology as it relates drug discovery, biological probe discovery and phenotypic characterization of small-molecule effects (siRNAs and chemical compounds) on cellular systems. BioPhenics is located on the Translational Research Department of the Institut Curie Research Center. Startup funding for the facility has been provided by the Institut Curie and French research agencies. BioPhenics operates with a philosophy of collaboration, rather than fee-for-service. The facility, which has existed for over 6 years, has enabled screening projects for different research groups in Europe, most of them located in cancer centers, aiming to benefit from the platform capabilities for identifying both the genes and pathways that mediate disease states and novel compounds that modulate these pathways. The facility provides basic and applied research teams with the technical resources and expertise needed to carry out high-content screens. These screens can be carried out using small molecule or siRNA libraries curated by BioPhenics or with custom libraries developed by researchers. BioPhenics is designed to function both as an intellectual base and a core research facility for researchers in their goal to develop novel treatments for disease. BioPhenics Scientific Staff provides the intellectual capital, collaborative opportunities and access to state-of-the-art technologies in chemical biology and participates in the training of future research scientists and health care practitioners.
Screening Technology
Equipments: The robotic platform is a flexible, modular, specialized system for the full automation of a wide variety of 96 and 384-well cell-based and biochemical assays. In addition to housing the instrumentation and robotics required for traditional high-throughput liquid handling (TECAN EVO, MAP TiterTek, Thermo Scientific Multidrop), the facility houses two cutting-edge High Content Image-based instruments (INCell 2000 and INCell 2200 systems) for small-molecule discovery research and analysis in fixed cells. The cell culturing laboratory ensures the continuous provision of cell culture samples for automated testing. They are located in a positive-pressure room fully equipped for preparation and maintenance of cell cultures in a safe and sterile environment. Standard operating procedures are implemented to ensure the continuous production of consistent high-quality cell-based assays.
Compound Library Resources: BioPhenics provides research investigators access to human genome-wide or family-wide siRNAs libraries as well as small molecule chemical compounds that can be used as tools to advance discovery basic and translational research of human biology and disease and in drug discovery. Our compound libraries fall into two main categories: 1. Approved drugs and compounds of known bioactive and clinical properties aiming the “repurposing” of known drugs, which allows for rapid translation from screening hits to the clinic and 2. Custom designed drug-like diversity sets, which are collections with high structural diversity while satisfying many published criteria for drug- and lead-likeness..
Database Resources: An in-house bioinformatics data management system is also linked to the facility to ensure reliable treatment and traceability of all experimental workflow. BioPhenics maintains the database infrastructure necessary to record comprehensive siRNA and chemical information together with the associated high-content biological and analytical data, offering consistent and traceable chemical and biological data management and analysis. The platform has investing a lot in basic data mining and the advanced informatics approaches needed to handle the large data sets that are produced by high-throughput and high-content screens.
Major expertise:
Compound Library Resources: BioPhenics provides research investigators access to human genome-wide or family-wide siRNAs libraries as well as small molecule chemical compounds that can be used as tools to advance discovery basic and translational research of human biology and disease and in drug discovery. Our compound libraries fall into two main categories: 1. Approved drugs and compounds of known bioactive and clinical properties aiming the “repurposing” of known drugs, which allows for rapid translation from screening hits to the clinic and 2. Custom designed drug-like diversity sets, which are collections with high structural diversity while satisfying many published criteria for drug- and lead-likeness..
Database Resources: An in-house bioinformatics data management system is also linked to the facility to ensure reliable treatment and traceability of all experimental workflow. BioPhenics maintains the database infrastructure necessary to record comprehensive siRNA and chemical information together with the associated high-content biological and analytical data, offering consistent and traceable chemical and biological data management and analysis. The platform has investing a lot in basic data mining and the advanced informatics approaches needed to handle the large data sets that are produced by high-throughput and high-content screens.
Major expertise:
- 2-D cell based HCS (fixed cells only)
- Highly diverse phenotypic assays portfolio
- Assay Development and Validation
- Assay Miniaturization and Automation
- Early drug discovery process from target identification to lead molecule characterization
- Internal R&D projects
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Selected Team Publications
- Ablain J, Leiva M, Peres L, Fonsart J, Anthony E, de Thé H. Uncoupling RARA transcriptional activation and degradation clarifies the bases for APL response to therapies.J Exp Med. 2013 Mar 18.
- Boncompain G, Divoux S, Gareil N, de Forges H, Lescure A, Latreche L, Mercanti V, Jollivet F, Raposo G, Perez F. Synchronization of secretory protein traffic in populations of cells. Nat Methods. 2012 ;9(5):493-8.
- Garcia-Cattaneo A, Gobert FX, Müller M, Toscano F, Flores M, Lescure A, Del Nery E, Benaroch P. Cleavage of Toll-like receptor 3 by cathepsins B and H is essential for signaling. Proc Natl Acad Sci U S A. 2012 5;109(23):9053-8.
- Pauwels E, Surdez D, Stoll G, Lescure A, Del Nery E, Delattre O, Stoven V. A probabilistic model for cell population phenotyping using HCS data. PLoS One. 2012;7(8).
- Cascone I, Selimoglu R, Ozdemir C, Del Nery E, Yeaman C, White M, Camonis J. Distinct roles of RalA and RalB in the progression of cytokinesis are supported by distinct RalGEFs. EMBO J. 2008;27(18):2375-87.