Main aim:
Validate an increased eATP level as a marker of the inflammatory microenvironment. Identify paradigmatic inflammatory and infectious diseases characterized by a key P2XR involvement. Identify the mechanistic link between inflammation eATP increase, P2XR activation, the release of pro- inflammatory mediators.
Main objectives:
1) Develop and validate novel in vivo probes for the measurement of eATP.
2) Collect, review, and analyze data on inflammatory conditions involving eATP and P2XRs.
3) Summarise current data on P2XR involvement in bacterial sepsis and infections caused by intracellular pathogens, focusing on emerging viral infections.
4) Development of P2XR-based diagnostic and drugs.
5) Training of Young researchers and Innovators in in vivo eATP measurement and P2XRs function in immune cells.
Task 1.1: Design and engineering of novel ratiometric bioluminescent probes based on luciferase prototype. This work is ongoing, and a candidate probe based on a bicistronic luciferase/renilla construct has been engineered. Further evolutions of this lead probe will be developed. These probes will be shared within the network and specific training schools will be organized. Joint applications to European funding bodies to support synergy fellowships for Young Researchers and Innovators will be made, and methods and consensus papers describing novel molecular probes will be published.
Task 1.2: Provide definitive evidence pro or against a causative role of P2XRs in the pathogenesis and progression of selected infectious, autoinflammatory, and autoimmune diseases.
Task 1.3: Organize a training school on purinergic signalling and eATP.
