Signalling of Minor Pocket Agonists at CXCR4

The following project, SMiPAX4, conducted in the academic group of Jean-Philippe Herbeuval (Univeristy of Paris, France), is at the cross section of immunology and pharmacology.

Moreover, due to its direct application potential and the subsequent industrial placement to deepen the acquired knowledge at Sanofi it is also cross sectional between academia and industry.

The main objective of the project is to understand the mode of action of small molecules, functionally causing a reduction of immune response, binding into the minor binding pocket of the G protein coupled receptor CXCR4.

The signalling cascade as well as the implication of different expression levels of the target CXCR4 will be explored through different biochemical techniques.

Protein-protein interactions will be identified using Bioluminescence energy transfer (BRET) techniques, increase or decrease of second messenger molecules will be identified using biosensors, and phosphorylation states, up- or downregulation of (signalling) proteins will be measured using flow cytometry or western blotting.

Inflammation of cells when controlling the impact of silencing certain signalling molecules will be controlled by measuring the levels of inflammation markers.

Due to the projects implication in (auto)immune and other inflammation diseases it is relevant for cluster 1, Health, of the Horizon Europe programme.

The project shows great potential in the area of impact due to its unique target potentially helping people that do not respond well to already approved medication.

Both, the dissemination of results producing multiple publications in peer reviewed journals, talks and posters at scientific meetings as well as the potential of creating market within the EU are very probable with completion of this project.