Schizophrenia is a severe psychiatric disease, that affects more than 23 million persons in the world and close to 600 000 in France. That represents around 1% of the global population, with men being more affected than women. Schizophrenia is characterized by psychopathological, cognitive, and neurobiological abnormalities, and deficiency in perception, emotion and social behaviour. The frequency, intensity and type of symptoms are highly variable among individuals, resulting in great heterogeneity in clinical presentation. This pathology is also associated to metabolic disturbances, including abnormalities in lipid levels both in the brain and peripheral tissues. Most schizophrenia treatments employ the use of antipsychotics, whose main therapeutic target is the D2R, a G-protein coupled receptor (GPCR). Drug efficacy is still highly variable between patients, due in part to the fact that antipsychotics also target other GPCRs both in monomeric and heteromeric forms. Due to recent data on the potential allosteric modulation of the D2R and other GPCRs activity by lipids, and their impact in receptor heteromerization, the “membrane hypothesis of schizophrenia” may be explained by changes in intracellular signalling as a consequence of lipid-triggered D2R heterodimerization. Some studies suggest an impact of polyunsaturated fatty acids (PUFA) and cholesterol on the heterodimerization of D2R with adenosine 2A receptor. These two receptors are at their highest expression level in the brain structures involved in schizophrenia physiopathology. Plus, a decrease in the formation of these heteromers has been observed post-mortem in schizophrenic patients, and in animal schizophrenia model, compared to healthy subjects. This heteromer reduction may be correlated with the altered lipid profiles also observed post-mortem in schizophrenic patients, but this hypothesis has never been validated. SCHIZOLIP aims to investigate the role of membrane composition on D2R heteromerization and its impact on antipsychotic activity. To do so, studies on HEK293 cells and reconstituted model membranes will be performed. Various biophysical methods will be carried out: Forster Resonance Energy Transfer (FRET), Proximity Ligation Assay (PLA), Plasmon Waveguide Resonance (PWR), Microscale Thermophoresis (MST). In fine, this project will allow a better understanding of the mechanisms of antipsychotics, namely the parameters that modulate their pharmacological activity, therefore opening new perspectives for the development of innovative therapeutic strategies.