Lille Platforms in Biology & Health – PLBS – UMS 2014 – US 41
ARIADNE comprises two platforms, ARIADNE-Screening and ARIADNE-ADMEWorking independently but in a complementary manner, their objective is to discover small chemical molecules useful in therapeutics or for exploring living organisms, and to characterize their ADME properties. ARIADNE-Screening brings together a range of expertise and equipment dedicated to screening biological disruptors such as small chemical molecules or siRNA libraries. ARIADNE-ADME It allows us to quantify the parameters that characterize the ability of molecules to be Absorbed, Distributed, Metabolized and Eliminated in vivo (ADME).
ARIADNE-Screening consists of three platforms. The HTS platform allows for the miniaturization of cell-based and non-cell-based pharmacological assays and high-throughput screening of chemical libraries. It enables medium-throughput evaluation of the activity of chemical series undergoing optimization and exploration of their mechanism of action. The HCS-L2 and HCS-L3 platforms for High Content Screening allow for high-throughput, high-content quantitative microscopy screening in a biosafety level 2 or 3 (BSL-2 or BSL-3) environment.
Expertise and services offered
The platform brings together a range of expertise and equipment dedicated to screening small chemical molecules or siRNA libraries. The equipment chain allows for the complete or partial automation of screening steps, from the plating of disruptors from chemical or siRNA libraries to the reading of results. The staff's expertise and technical skills enable the development of high-throughput, miniaturized (96-well, 384-well plates) and automated assays for in vitro, in bacterio, or in cellulo screening, on targets or phenotypic samples. ARIADNE benefits from access to chemical libraries, including the regional chemical library of approximately 200.000 chemical molecules, as well as siRNA and miRNA libraries. The platform also possesses expertise in cell labeling for cell homing using CRISPR-Cas9 approaches.
The equipment is located in biosafety level 1 to 3 laboratories. The HTS platform in LNSB1 allows for library management and high-throughput screening on multimode plate readers (with measurements in fluorescence, luminescence, absorbance, etc.). The HCS platforms for high-content screening, installed thanks to the Equipex ImagInEx BioMed project and the support of the European Research Council, are based on an automated and quantitative confocal microscopy technique. A first imaging system (IN cell Analyzer 6000) is fully automated in LNSB2. A second system (IN cell Analyzer 6500) is available in LNSB3. This so-called "non-destructive" technology allows for the monitoring of the same sample over time, both in the short term (dynamic phenomena) and the long term (kinetics), and enables the simultaneous measurement of several parameters on the same biological sample.
Many tests can be implemented: enzymatic tests, phenotypic or target cell tests, in vitro or in cellulo protein-protein interactions, Thermal Shift Assay (TSA) and target engagement monitoring… The use of Echo acoustic technology for the transfer of liquid nanodroplets makes it possible to prepare screening plates and to test molecules in combination and in dose response.
Applications for ARIADNE-Screening can be sent by email to the scientific lead. They will be discussed with the project leader and then a feasibility study will be conducted. Projects meeting the specifications will be accepted in the order they are received. Depending on the project, ARIADNE-Screening staff can train users for independent but paid access to the platform, prepare quotes for services, collaborate on fundraising efforts, etc. Each project is monitored by a member of the steering committee and the technical lead.
Within the framework of a partnership agreement, projects can be pursued with Ariadne-Criblage experts or their collaborators, focusing on target characterization and modulator optimization: target identification and engagement, medicinal chemistry, measurement of physicochemical properties, ADME studies, and pharmacokinetics in rodents. This latter work can be carried out using the platform ARIADNE-ADME.
News
The platform is organizing a thematic school on screening, which will take place in the Hauts-de-France region from September 20th to 23rd, 2022. Registration is available on the website of the...school.
ARIADNE's technicians, engineers and researchers have committed themselves to the search for a treatment against the Covid-19 pandemic:
- An active molecule against SARS-CoV-2 infection in vitro was discovered by screening a library of 2000 drugs on the HCS system in LNSB3 using cells. This discovery resulted from a collaboration with Dr. Sandrine Belouzard and Dr. Jean Dubuisson of the Lille Center for Infection and Immunity (IPL) and researchers from the company Apteeus.
- High-tensile screening (HTS) of the entire ARIADNE library (approximately 100,000 compounds) identified several chemical series active against the SARS-CoV-2 3CLPro protease at sub-micromolar concentrations. This project is being conducted with Dr. Julie Charton of unit U1177.
Members
DEPREZ Benoît
Director UMR1177 Inserm - Professor PhD, Pharm University of Lille
N. ORCID: 0000-0002-2777-4538
Sandrine WARENGHEM
Assistant Engineer IPL, U1177
Team contact
Publications
SLAS Discov 25, 783-791.
High-Throughput Image-Based Aggresome Quantification.
PLoS One 15, e0227224.
Intracellular and in vivo evaluation of imidazo[2,1-b] thiazole-5-carboxamide anti-tuberculosis compounds.
SLAS Discov 25, 207–214.
Drug Target Engagement Using Coupled Cellular Thermal Shift Assay-Acoustic Reverse-Phase Protein Array.
Science 355, 1206–1211.
