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Physiological roles of the Ribotoxic Stress Response

Total Cost €


EC-Contrib. €






 PHYRIST project word cloud

Explore the words cloud of the PHYRIST project. It provides you a very rough idea of what is the project "PHYRIST" about.

impairment    am    unravel    first    cells    investigation    cancer    cancers    triggered    ribotoxins    signalling    hence    pathological    sunlight    reactions    yield    nematodes    zak    uncover    diverse    mice    ricin    sum    impaired    quality    mapkkk    inhibition    activation    implications    organisms    mediated    detrimental    ko    connections    irradiation    putative    remedy    map    origins    lifespan    molecular    rsr    aging    underlying    despite    uv    team    structural    activates    jnk    surveys    therapy    chemotherapeutics    powerful    treat    functional    kinases    found    skin    unknown    inflammation    integrity    groups    proximal    elucidate    encouraged    rewardingly    p38    presented    prevent    infection    cellular    translation    ribosomes    knockout    ribotoxic    mouse    line    decades    deregulation    arising    phyrist    human    regulation    constitutes    fatal    defective    contributor    vivo    relevance    critical    inflammatory    drug    initiate    physiological    bacteria    ribotoxin    deficient    contributes    stress    position    refractory    protein    hypothesize    radiation    producing   

Project "PHYRIST" data sheet

The following table provides information about the project.


Organization address
address: NORREGADE 10
postcode: 1165

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Denmark [DK]
 Total cost 1˙997˙678 €
 EC max contribution 1˙997˙678 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2019-COG
 Funding Scheme ERC-COG
 Starting year 2020
 Duration (year-month-day) from 2020-06-01   to  2025-05-31


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    KOBENHAVNS UNIVERSITET DK (KOBENHAVN) coordinator 1˙997˙678.00


 Project objective

The ribotoxic stress response (RSR) surveys the structural and functional integrity of ribosomes and is triggered by diverse groups of ribotoxins (e.g. ricin), UV irradiation and some chemotherapeutics. When presented with impaired ribosomes, the proximal MAPKKK ZAK activates MAP kinases p38 and JNK to initiate a powerful inflammatory response. This signalling contributes to the detrimental reactions to ribotoxins and fatal side effects of cancer therapy. However, despite decades of research into the RSR, the physiological relevance of the underlying pathway in whole organisms is unknown. I hypothesize that the RSR constitutes a general translation quality control pathway and hence I aim to uncover the physiological and pathological implications of RSR impairment in mice and nematodes.

In one line of investigation, I will elucidate the connections between UV radiation and RSR-mediated p38 activation. I hypothesize that this signalling pathway is critical for sunlight-induced skin inflammation and development of skin cancers of different cellular origins. Rewardingly, we found that cells from our ZAK knockout (KO) mice are refractory to UV-induced p38 activation, which is a significant contributor to skin cancer development. My team has also observed deregulation of protein translation in RSR-deficient human and mouse cells, and a reduced lifespan of ZAK KO nematodes. Thus encouraged, I will determine the impact of the RSR pathway on cancer development and aging processes in mice, and I will unravel the molecular connections between defective ribosomes, RSR activation and regulation of translation. Finally, I am in a unique position to evaluate the RSR as a putative drug target and I will investigate the potential of ZAK inhibition to treat or prevent skin cancer, and to remedy inflammation arising from infection with ribotoxin-producing bacteria. In sum, PHYRIST will yield the first detailed insight into the in vivo relevance of the ribotoxic stress response.

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The information about "PHYRIST" are provided by the European Opendata Portal: CORDIS opendata.

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