Datos del proyecto:
- Organismo financiador: Comisión Europea
- Programa: Consolidator Grants , ERC-2013-CoG, panel LS6
- Nº proyecto: Proposal no. 614578
- Nº de socios / regiones participantes: Proyecto unipersonal
- Participantes del Sistema Regional de Salud: IMIB (a través de la FFIS como su órgano de gestión)
- Fecha de inicio y fin: 01/09/2014 - 31/08/2020
- Duración: 60 meses inicialmente; prórroga 1 año
- Financiación total EU recibida para el proyecto: 1.794.948 €
- Áreas: Inflamación e inmunidad
- Web del proyecto: https://erc.europa.eu/regulation-inflammatory-response-extracellular-atp-and-p2x7-receptor-signalling-through-and-beyond-i
Resumen del proyecto:
Inflammatory diseases affect over 80 million people worldwide and accompany many diseases of industrialized countries, being the majority of them infection-free conditions. There are few efficient anti-inflammatory drugs to treat chronic inflammation and thus, there is an urgent need to validate novel targets. We now know that innate immunity is the main coordinator and driver of inflammation. Recently, we and others have shown that the activation of purinergic P2X7 receptors (P2X7R) in immune cells is a novel and increasingly validated pathway to initiate inflammation through the activation of the NLRP3 inflammasome and the release of IL-1β and IL-18 cytokines. However, how NLRP3 sense P2X7R activation is not fully understood.
Furthermore, extracellular ATP, the physiological P2X7R agonist, is a crucial danger signal released by injured cells, and one of the most important mediators of infection-free nflammation.
We have also identified novel signaling roles for P2X7R independent on the NLRP3 inflammasome, including the release of proteases or inflammatory lipids.
Therefore, P2X7R has generated increasing interest as a therapeutic target in inflammatory diseases, being drug like P2X7R antagonist in clinical trials to treat inflammatory diseases.
However, it is often questioned the functionality of P2X7R in vivo, where it is thought that extracellular ATP levels are below the threshold to activate P2X7R.
Acciones que desarrolla el grupo de investigación / innovación en la Región de Murcia:
This project leads to consider a number of ethical issues and corresponding regulations; therefore the applicant is well aware of the fact that research with live mice raises various ethical questions and therefore will work in accordance with actual legislation. Animal models will be used to study crucial issues of extracellular ATP and P2X7 receptor function in in vivo inflammatory process.
Reflexiones del grupo de investigación / innovación regional:
The overall significance of this proposal relays to elucidate how extracellular ATP controls host-defence in vivo, ultimately epicting P2X7R signaling through and beyond inflammasome activation. We foresee that our results will generate a leading innovative knowledge about in vivo extracellular ATP signaling during the host response to infection and sterile danger.