Laboratories : GIN and IBS- 01/10/2022 - 30/09/2025

Thesis project holders : Mireille ALBRIEUX and Christophe MOREAU
Young thesis researcher : Guillaume AUDIC

Abstract: In the context of Alzheimer’s disease, dyshomeostasis caused by amyloid-β (Aβ) peptide is proposed as one of the early events of the disease and is associated with a disruption of neuronal activity. In the brain, neuronal activity is strongly regulated by astrocytes, which wrap around synapses to control their activity. This particular structure is known as a tripartite synapse. It has previously been shown that astrocytes are targeted by the Aβ peptide, inducing early and multimodal synaptotoxicity. The identification of the astrocytic calcium channel, transient receptor potential ankyrin 1 (TRPA1), in the rapid onset of toxicity and neuronal dysfunction suggests that it may be a priority target in the development of a therapeutic strategy. In this project we aimed to describe the molecular and structural mechanisms based on the activation of TRPA1 by the Aβ peptide. Using a transdisciplinary approach combining functional characterization by electrophysiology and structural characterization by cryo-electron microscopy, we define the TRPA1-Aβ complex. Biophysical techniques help to obtain the constants defining this molecular interaction.
 

Publications:
Audic G., Pierre A., Rodriguez Q., … Albrieux M., Moreau C. Human amyloid-β peptide directly interacts with human TRPA1 leading to an astrocytic Ca2+ entry : from molecular to pathophysiological dimensions. Mansucript in preparation

Terral O, Audic G, Claudel A, Magnat J, Dupont A, Moreau C, Delacour C. Graphene Field-Effect Transistors for Sensing Ion-Channel Coupled Receptors: Toward Biohybrid  anoelectronics
for Chemical Detection. Advanced Electronic Materials 2024; 10:2300872.

Pacalon J*, Audic G*, Magnat J, Philip M, Golebiowski J, Moreau CJ*, Topin J*. Elucidation of the structural basis for ligand binding and translocation in conserved insect odorant receptor co-receptors. Nature Communications 2023; 14: 8182. *:contributed equally.

Moreau CJ, Audic G, Lemel L, García-Fernández MD, Nieścierowicz K. Interactions of cholesterol molecules with GPCRs in different states: A comparative analysis of GPCRs' structures. Biochim. Biophys. Acta Biomembr. 2023; 1865:184100