Bagnols-sur-Cèze, France – June 26, 2008 – Cisbio Bioassays, a member of IBA group and a global developer of HTRF® (Homogeneous Time-Resolved Fluorescence) technology and services used in assay development and drug screening, today announced findings from its R&D collaboration with the Department of Molecular Pharmacology at the Institute of Functional Genomics (IGF) focused on the structural organization of G-Protein Coupled Receptors (GPCRs). The results of the collaboration, which describe new methodologies for analyzing receptors at the cell surface of living cells, allow for a better understanding of the spatial structure, mechanisms, and functionality of GPCRs, one of the most important target classes investigated in drug discovery research.
Using a combination of HTRF and SNAP-Tag™ technologies, Cisbio and IGF set up TR-FRET (Time-Resolved Fluorescence Resonance Energy Transfer) assays to demonstrate that GPCRs can adopt a specific organization on the cell surface. These investigations show, in particular, that different class C GPCRs can assemble into either strict dimers or larger oligomers. TR-FRET, on which HTRF is based, presents numerous advantages over assay technologies such as FRET and BRET (Bioluminescence Resonance Energy Transfer) for analyzing living cells as it offers a higher signal to noise ratio and discriminates between the cell surface protein and the intracellular cell compartment. The findings illustrate new methods for rapidly and quantitatively analyzing cell surface signaling complexes in living cells in a high throughput format that can potentially be applied to drug screening processes. This improved analysis of cell-to-cell communication can, in turn, facilitate research and discovery of new therapeutics.
Articles detailing the methodologies used were published in two journals, “Functioning of the dimeric GABAB receptor extracellular domain revealed by glycan wedge scanning” in The European Molecular Biology Organization Journal and “Cell-surface protein-protein interaction analysis with time-resolved FRET and snap-tag technologies: application to GPCR oligomerization” in Nature Methods.
“This latest collaboration is an example of how Cisbio’s R&D expertise in chemistry, technology and biology were combined to bring technical breakthroughs to the GPCR field,” said Eric Trinquet, Head of Technology and Chemistry at Cisbio, who supervised the research. “Our dedication to R&D, innovation and our partnerships with top-notch research institutes like IGF position us at the forefront of GPCR research.”
Since 2001, Cisbio has been working on various projects in close collaboration with IGF, a renowned research institute in Montpellier, France specializing in GPCR studies and molecular pharmacology; IGF was first to report on GPCR activation by the main neurotransmitter glutamate. In 2006, Cisbio was awarded a $1.9 million grant by France’s National Research Agency (ANR) to establish an HTS-compatible technology for the quantification of biomolecular interactions in living cells targeting GPCRs. The published findings are the fruit of the work made possible by this award. Cisbio will continue to collaborate with IGF in this sector.
"The existence of GPCR oligomers has long been a matter of intense debate. Thanks to the TR-FRET/SNAP-Tag approach, we have been able to provide new and convincing evidence for the existence of such complexes that offer a number of possibilities to design more selective and more effective drugs," said Jean-Philippe Pin, Head of IGF’s Department of Molecular Pharmacology and supervisor of the project. "This technology is so easy to use that we are now working on new assays allowing the analysis of receptor complexes in native tissues, and new efficient ways to quantify ligand-receptor interaction."
Cisbio has a full technological GPCR platform incorporating HTRF, its highly sensitive, robust technology for the detection of molecular interactions of proteins in vitro. Earlier this year, this portfolio was reformatted with the Lumi4™-Tb terbium cryptate for increased sensitivity and an enhanced signal-to-noise ratio. These latest findings will lead to the development of new reagents associated with Lumi4-Tb for Cisbio’s GPCR product portfolio, specifically in the field of cell surface receptors. In the meantime, these assays are available to Cisbio’s customers as part of its custom assay development services.
About Cisbio Bioassays
Cisbio Bioassays is a global developer of products and technologies used in nuclear medicine, in vitro diagnostics and assay development for drug screening procedures. The company pioneered the field of homogenous fluorescence methodologies via its proprietary technology, HTRF®, a highly sensitive, robust technology for the detection of molecular interactions and widely used by the pharmaceutical industry for the high throughput screening stage of drug development. In addition, Cisbio Bioassays produces a selection of biological reagents and methods used by pharmaceutical and biotechnology companies, as well as contract research organizations (CROs). Headquartered in Bagnols-sur-Cèze, France, Cisbio Bioassays is owned by the Belgium company IBA, has facilities in Bedford, MA, U.S.A. and markets its products worldwide through a network of distributors. For more information about Cisbio and HTRF, log onto www.htrf.com.
IBA is a developer of precision solutions for cancer diagnosis and treatment. It also offers sterilization and ionization solutions for optimal everyday hygiene and safety. Listed on the pan-European stock exchange EURONEXT, IBA is included in the BelMid Index. For more information about IBA, log onto www.iba-worldwide.com.
IGF is an internationally recognized research institute specialized in the study of the functioning and role of signaling molecules involved in cell-to-cell communication. Based in Montpellier, France, IGF regroups researchers from France’s CNRS (National Center for Scientific Research), INSERM (National Institute of Health and Medical Research), and the University of Montpellier into 5 scientific departments: neurobiology, molecular pharmacology, physiology, endocrinology and oncology. These departments are comprised of 19 research teams that specialize, in particular, in GPCRs, ionic channels, synapsis molecules, and endocrine, neuroendocrine and oncological signalization. For more information, log onto www.igf.cnrs.fr.
HTRF® is a registered trademark of Cisbio Bioassays.
Lumi4™-Tb is a trademark of Lumiphore, Inc. Cisbio holds the exclusive rights to Lumi4-Tb for the drug discovery field of use.
SNAP-Tag™ is a trademark of Covalys. Cisbio holds the exclusive rights to apply SNAP-Tag technology to TR-FRET applications.
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