Team Guillaume LEBON – Cyril GOUDET

Neuromodulation is a slow adaptation of neuronal activity, resulting from the action of neuromediators on metabotropic receptors, mainly G protein-coupled receptors (GPCRs). In most neurological disorders, a loss of balance between excitatory and inhibitory systems is observed, resulting from a deregulation of neurotransmission and neuromodulation mechanisms. From a therapeutic point of view, GPCRs are therefore particularly interesting targets, capable of controlling brain activity, as illustrated by the fact that around half the drugs on the market act directly or indirectly on GPCRs.

Among the disorders of the nervous system, we are particularly interested in chronic pain and its neuromodulation by two neuromediators, adenosine and glutamate, but also in Alzheimer’s disease, autism spectrum disorders and schizophrenia, more specifically in the case of glutamate receptors.

We are developing molecular tools such as small molecules and photocontrollable ligands that enable us to control the activity of these receptors, in particular with spatio-temporal resolution of their biological activity. We are analysing the conformational changes associated with receptor activity at the atomic scale in order to gain a better understanding of their molecular functioning, using X-ray diffraction methods and electron microscopy under cryogenic conditions.

Our projects are positioned at the chemistry-biology interface and combine structural biology, molecular, cellular and preclinical neuropharmacology and photopharmacology to explore the structure and function of adenosine and glutamate receptors, their signalling complexes and their functional interactions at the animal, cellular or molecular level.