H2020Staff exchange2016–2019

EPIC · Exploiting Protein Complexes that Induce Cell-death

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2016-01-01 → 2019-12-31
EU contribution
€607,500
Participants
6
Scheme
MSCA-RISE

Lines connect the coordinator with its partners.

Results in brief

Exploiting Protein Complexes that Induce Cell-death

Programmed cell death (PCD) occurs in many pathological situations from inflammation to ischaemia. PCD is also the mechanism through which many anti-cancer therapies act. After 20 years of PCD research it is now clear that there are several distinct PCD pathways, including apoptosis, necroptosis and pyroptosis. Many PCD processes appear to be regulated by the formation of large protein complexes that initiate cell the molecular events that eventually kill the cells. For example, the formation of a complex called the apoptosome induces apoptosis, formation of the necrosome induces necroptosis and formation of the inflammasome causes pyroptosis. As these protein complexes determine cell fate, blocking complex formation in diseases where cell death is unwanted or inducing complex formation in diseases where cell death is desirable could be a valuable therapeutic approach. Realizing this aim is currently limited by the absence of assays for complex formation that are suitable for screening purposes. Solving this problem requires a multi-disciplinary approach and the integration of research activities that are spread across different research groups. Completion of the project will provide new approaches to detect and investigate protein complexes that determine cell fate, providing new strategies for both drug-discovery and for in vitro toxicity testing.

Data: CORDIS, © European Union

Project objective

The formation of specific protein complexes are key events in life-and-death decisions made by cells. Inappropriate decisions underpin a plethora of disease conditions from degenerative diseases to cancer while the role of the complexes in these processes make them important therapeutic targets. Our ability to develop small molecules to target death-inducing protein complexes has been hampered by an inability to measure complex formation in cells in real-time and by the absence of robust high-throughput assays for the discovery of new lead molecules that target these complexes. The proposed network (EPIC) will address both of these problems by developing new approaches to measure necrosome and apoptosome formation in real-time as well as new high-throughput and high-content screening assays using Fluorescence resonance transfer and split-luciferase technologies.EPIC will conform with the H2020 work programme by integrating research activity, novel reagents and expertise across Europe and world through the mobility, knowledge transfer and training of experienced and early stage researchers from within and without the EU. EPIC will realise the potential of researchers through the development of new skill-sets, the transfer new skills between academia and industry, and the development of career opportunities for EU ESRs and ERs. A key part of this activity is the mobility of non-EU researchers and the inward transfer of essential knowledge from outside the EU to benefit EU-based research. Establishment of EPIC through RISE will generate lead molecules with demonstrable utility and knowledge that will underpin applications to national funding agencies to sustain the communal effort beyond the life of the RISE award. It will also generate intellectual property that will enable the network to approach biotech and pharma to form academia-industry partnerships that will further develop small molecule leads as therapeutics.

Original text from CORDIS.

Participants

  • UNIVERSITY OF GALWAY · GalwayCoordinatorIreland
  • FUNDACION DE LA COMUNIDAD VALENCIANA CENTRO DE INVESTIGACION PRINCIPE FELIPE · ValenciaSpain
  • GOETEBORGS UNIVERSITET · GoeteborgSweden
  • PROTOQSAR 2000 SL · ValenciaSpain
  • TARBIAT MODARES UNIVERSITY (INSTRUCTOR'S TRAINING UNIVERSITY) · TEHRANIran
  • VIB VZW · ZWIJNAARDE - GENTBelgium

Links

Data: CORDIS, © European Union