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signaling bias

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Pharmacological characterization and biased signaling:

We are interested in characterizing the pharmacological effects induced by native or recombinant hormones, chemical or peptide ligands, or antibody fragments, by quantifying their signaling selectivity capacity.

This work aims to understand the mechanisms of signaling and intracellular traffic activated by these different ligands, the data generated thanks to the biased ligands feeding the modeling approaches aimed at predicting the physiological consequences of the different mechanisms induced at the molecular and cellular levels.

Development of new innovative pharmacological tools:

We develop nanobodies (VHH) against our targets of interest in order to modulate their biological activity. Our objective is to identify, for the GPCRs involved in the reproduction and/or the control of social interactions, VHHs presenting various pharmacological activities in order to selectively control the activated signaling pathways and to study their respective physiological impacts.

Our work on the development of VHH aims to control the activity of our targets of interest with potential applications in human medicine and animal husbandry in the fields of non-hormonal control of reproduction and social interactions (ie autism spectrum disorder , animal wellbeing). The developed VHHs also represent unique tools for understanding signaling mechanisms and their physiological consequences, including in vivo

List of funding obtained:

1. Bill & Melinda Gates Foundation, Contrabody, Eric REITER (2021-2023, US$1.8 M), 1 international academic partner, 2 industrial partners, coordinator.

2. Center Val de Loire Region, ARD2020 Biomedicines Phase 3, SELMAT, Eric REITER (2020-2023, 630 K€), 3 academic partners, 1 industrial partner, coordinator.

3. ERC starting grant, Lucie PELLISSIER (2020-2025), New molecular targets and proof-of-concept therapies for Autism Spectrum Disorders (THERAUTISM).

4. Center Val de Loire Region, APR IR, INTACT, Pascale CRÉPIEUX (2019-2022), MCSaF, coordinator.

5. ANR YDOBONAN, Vincent AUCAGNE (2021-2024) CBM CNRS Orléans, collaborator.

6. Center Val de Loire Region, APR IR, NeuroMAbster, Séverine MORISSET-LOPEZ (2018-2022) CBM CNRS Orléans, INEM CNRS Orléans, collaborator.

7. Center Val de Loire Region, APR IR, LIPICABS, Marie POTIER-CARTEREAU (2018-2022), N2C INSERM, Tours, Synthelis, collaborator.

8. LabEx MabImprove, Hervé Watier (2012-2025), partner team.

Team people involved:

PhD students: Anielka Zehnaker, Camille Gauthier, Pauline Raynaud, Caroline Gora, Juliette Gourdon + ARC

Postdocs: Vinesh Jugnarain, Maya Haj-Hassan, + Gates 2

ITA CDD: Amandine Vallet, Laeticia Mathias, Lucile Drobecq, Océane Vaugrente

ITA: Thomas Boulo

Researchers: Pascale Crépieux, Lucie Pellissier, Anne Poupon, Frédéric Jean-Alphonse, Gilles Bruneau, Eric Reiter, Yves Combarnous, Danièle Klett, Romain Yvinec

Scientific communities: GDR Reproscience, IRN GPCRnet, LabEx MAbImprove, EPC Musca