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iPROTECTION SIGNED

Molecular mechanisms of induced protection against sepsis by DNA damage responses

Total Cost €

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EC-Contrib. €

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Partnership

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 iPROTECTION project word cloud

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

cellular    inflammation    tissue    silencing    validate    discovery    candidates    gain    overexpression    protection    unbiased    extraordinary    combination    anthracycline    aging    therapeutic    completely    biological    molecularly    critical    sepsis    physiological    mechanisms    inflammatory    homeostasis    conferring    transformative    rates    vitro    function    ultimately    inspire    limited    cell    activated    vivo    therapies    stress    understand    damage    systemic    severe    genetic    constructs    programs    surveillance    quality    lung    arising    mortality    shrna    bacterial    gene    poorly    sufficient    atm    central    independent    adenovirus    possibly    disease    mediated    core    lifespan    promise    model    perhaps    window    dna    cytoprotective    basic    burden    activation    life    prevent    drugs    organ    dependent    carry    infection    unknown    either    showing    anthracyclines    candidate    rescuing    tolerance    options    outside    strategies    treatment    identification    biochemical    opportunity   

Project "iPROTECTION" data sheet

The following table provides information about the project.

Coordinator
FUNDACAO CALOUSTE GULBENKIAN 

Organization address
address: AVENIDA BERNA 45
city: LISBOA
postcode: 1000
website: www.igc.gulbenkian.pt

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 Portugal [PT]
 Project website http://www.igc.gulbenkian.pt/lmoita
 Total cost 1˙985˙375 €
 EC max contribution 1˙985˙375 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-10-01   to  2020-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FUNDACAO CALOUSTE GULBENKIAN PT (LISBOA) coordinator 1˙985˙375.00

Map

 Project objective

Severe sepsis remains a poorly understood systemic inflammatory condition with high mortality rates and limited therapeutic options outside of infection control and organ support measures. Based on our recent discovery that anthracycline drugs prevent organ failure without affecting the bacterial burden in a model of severe sepsis, we propose that strategies aimed at target organ protection have extraordinary potential for the treatment of sepsis and possibly for other inflammation-driven conditions. However, the mechanisms of organ protection and disease tolerance are either unknown or poorly characterized. The central goal of the current proposal is to identify and characterize novel cytoprotective mechanisms, with a focus on DNA damage response dependent protection activated by anthracyclines as a window into stress-induced genetic programs conferring disease tolerance. To that end, we will carry out a combination of candidate and unbiased approaches for the in vivo identification of ATM-dependent and independent mechanisms of tissue protection. We will validate the leading candidates through adenovirus-mediated delivery of constructs for overexpression (gain-of-function) or shRNA for gene silencing (loss-of-function) to the lung, based on our recent finding that rescuing this organ is essential and perhaps sufficient in anthracycline-induced protection against severe sepsis. The candidates showing the most promise will be characterized using a combination of in vitro and in vivo genetic, biochemical, cell biological and physiological methods. The results arising from the current proposal are likely not only to inspire the design of transformative therapies for sepsis but also to open a completely new field of opportunity to molecularly understand core surveillance mechanisms of basic cellular processes with a critical role in the homeostasis of organ function and whose activation can ultimately promote quality of life during aging and increase lifespan.

 Publications

year authors and title journal last update
List of publications.
2016 Henrique G. Colaço, Luis F. Moita
Initiation of innate immune responses by surveillance of homeostasis perturbations
published pages: 2448-2457, ISSN: 1742-464X, DOI: 10.1111/febs.13730
The FEBS Journal 283/13 2020-04-23
2016 TR Velho, I Santos, P Póvoa, Moita Ferreira
Sepsis: the need for tolerance not complacency
published pages: , ISSN: 1424-7860, DOI: 10.4414/smw.2016.14276
Swiss Medical Weekly 2020-04-23
2017 Miguel P. Soares, Luis Teixeira, Luis F. Moita
Disease tolerance and immunity in host protection against infection
published pages: 83-96, ISSN: 1474-1733, DOI: 10.1038/nri.2016.136
Nature Reviews Immunology 17/2 2020-04-23
2017 Ana Neves-Costa, Luis F. Moita
Modulation of inflammation and disease tolerance by DNA damage response pathways
published pages: 680-698, ISSN: 1742-464X, DOI: 10.1111/febs.13910
The FEBS Journal 284/5 2020-04-23
2019 Isa Santos, Henrique G Colaço, Ana Neves-Costa, Elsa Seixas, Tiago R Velho, Dora Pedroso, André Barros, Rui Martins, Sebastian Weiss, Didier Payen, Sebastian Weiss, Hyon-Seung Yi, Minho Shong, Luis F Moita
CXCL5-mediated recruitment of neutrophils into the peritoneal cavity of Gdf15-deficient mice protects against abdominal sepsis
published pages: , ISSN: , DOI: 10.1101/613901
BioRxiv 2020-04-23

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