The Biofarma research group from the University of Santiago de Compostela (USC) offers a technology platform specialized in GPCRs pharmacology allowing multiplexing different signaling pathways in the same cell population. This platform would allow the detection of biased ligands and/or allosteric modulators at GPCRs by simultaneously measuring cAMP formation, inositol phosphates accumulation, arachidonic acid release, calcium mobilization, β-arrestin translocation or ERK phosphorylation.
The Biofarma research group from the Universidad de Santiago de Compostela (USC) has set up the Innopharma pharmacogenomics platform at its facilities including state-of-the-art technologies for both pharmacogenomics and compound screening. The chemical biology/pharmacology divisions possesses a chemical library of 60,000 compounds and comprises fully automated laboratories for carrying out both target-based and phenotypic screening with technologies such as High Content Imaging, FLIPR, automated patch-clamp, Dynamic mass Redistribution or microfluidics mobility shift assays, among others. The group has a deep expertise in designing and executing High Throughput Screening campaigns and hit validation in translational secondary assays. This translational approach comes from the group integration in the Health Research Institute connected to the Clinical Hospital of Santiago, which allows access to patient samples and increases the translation of the results obtained up to clinical ‘Proof of Principle’. The group possesses a long track record in the early drug discovery field with more than 150 established collaborations with public research groups, 50 collaborations/agreements with biotech companies and 40 collaborations/agreements with pharmaceutical companies.
The USC partner offers a technology platform specialized in GPCRs pharmacology allowing multiplexing different signaling pathways in the same cell population. This platform allows the detection of GPCRs biased ligands and/or allosteric modulators. Thus, the effect of the compounds will be measured in a single assay by measuring simultaneously those pathways activated by the receptor. These pathways include cAMP formation, inositol phosphates accumulation, arachidonic acid release, calcium mobilization, β-arrestin translocation or ERK phosphorylation. This approach allows identifying biased ligands for any of the signaling pathways studied. GPCRs allosteric modulators will be identified by employing the same technology in the presence of the endogenous agonist of the GPCR under study. Allosteric ligands will be fully characterized by means of radioligand binding assays in order to confirm they are not binding to the orthosteric binding site.
100,000 (full commercial set) of the EU-OPENSCREEN ERIC compound library
The assays will be run by employing in-house developed methodologies based on FLIPR (Hamamatsu FDSS7000), HTRF (Tecan M1000 Pro, Perkin Elmer Enspire), radioactivity (Microbeta Trilux), luminescence (Hamamatsu FDSS7000, Tecan M1000 Pro, Perkin Elmer Enspire) and fluorescence imaging (Perkin Elmer Operetta).
Please note that this project includes the possibility of re-screening during potential chemical optimization under the medicinal chemistry call starting in 2021 (tentative date).
The prerequisite starting point to qualify for access is the availability of cell lines expressing the GPCR of interest and information about its culture. Stable cell lines are preferred over transient cell lines.
As specifics of the assay transfer procedure may vary between partner sites, the applicant and the individual sites will agree on the appropriate steps and logistics together.
Cell-based assays using cellular systems
drug discovery, small molecules, high-throughput screening, cell-based assays
June-01-2019 (20:00 CET)
September-30-2019 (20:00 CET)
Scientific contact: firstname.lastname@example.org
Technical contact: email@example.com
Machine/Methods contact: firstname.lastname@example.org