Explore the words cloud of the iPROTECTION project. It provides you a very rough idea of what is the project "iPROTECTION" about.
The following table provides information about the project.
FUNDACAO CALOUSTE GULBENKIAN
|Coordinator Country||Portugal [PT]|
|Total cost||1˙985˙375 €|
|EC max contribution||1˙985˙375 € (100%)|
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
|Duration (year-month-day)||from 2015-10-01 to 2020-09-30|
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|1||FUNDACAO CALOUSTE GULBENKIAN||PT (LISBOA)||coordinator||1˙985˙375.00|
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.
|year||authors and title||journal||last update|
Henrique G. ColaÃ§o, 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|
TR Velho, I Santos, P PÃ³voa, 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|
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|
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|
Isa Santos, Henrique G ColaÃ§o, Ana Neves-Costa, Elsa Seixas, Tiago R Velho, Dora Pedroso, AndrÃ© 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
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