Developers
I. Dorange, B. Breton, M. Coupal, M. Frauli, S. Schann.
Description of the technology
The BioSens-AllTM platform was implemented to interrogate the signaling complexity associated with GPCR activation. It consists of a combination of BRET-based biosensors each designed to follow one specific signaling event upon GPCR activation.
1. In a microplate, cells are co-transfected with the vector expressing the GPCR native sequence (no tag required) and the vectors for the expression of the desired biosensors.
2. Following protein-transient expression (48hrs after transfection), compounds are incubated with the cells and the activity of the biosensor is measured.
BioSens-AllTM platform offers a flexible service. With over 25 biosensors, the BioSens-AllTM platform constitutes a unique offering of integrated functional assays dedicated to the characterization of GPCR signaling. BioSens-AllTM enables the design of tailored studies (number and type of biosensors) reflecting investigators’ needs. Intracellular events measured within the
BioSens-AllTM services include:
- activation of protein Gαs, Gαi1, Gαi2, Gαi3, GαoA, GαoB, Gαz, Gα12, Gα13, Gαq, Gα11, Gα14, and Gα15/16,
- recruitment of β-arrestin 1 and 2,
- production of cAMP and calcium,
- activity of effectors TPR1, GRK2/3, PKC, p63, Merlin, and p115.
Advantages of
BioSens-AllTM studies:
- will rapidly deliver the signaling signature for the GPCR of choice (example: wild type, mutant or orthologous),
- no assay system bias (all cellular events measured with the same platform),
- no structural modification of the receptor.
Practical application
This technology is dedicatied to drug discovery.
BioSens-AllTM applications include but are not limited to:
- orthosteric and allosteric compound bias effects,
- signaling signature of wild-type receptors versus mutant variants,
- orphan receptor signaling signature determination (deorphanization),
- detection of receptor constitutive activity.
Laboratories
Domain Therapeutics, Neomed Institute, Montreal, Quebec, (Canada)
Links
http://www.domaintherapeutics.com/research-and-technology/biosens-all.html
Publications
Dorange, Ismet, et al. «
BioSens-All ™: A new technology dedicated to GPCR biased ligand drug discovery." ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY. Vol. 248. 1155 16TH ST, NW, WASHINGTON, DC 20036 USA: AMER CHEMICAL SOC, 2014.
Franchet, Christel, and Ismet Dorange. «GPCR binding technologies: an overview." Current topics in medicinal chemistry 15.24 (2015): 2476–2483.