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CFZEBRA

Balancing the immune response in cystic fibrosis: using zebrafish models of infection and inflammation to uncover new therapeutic approaches

Total Cost €

0

EC-Contrib. €

0

Partnership

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 CFZEBRA project word cloud

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

cystic    larvae    recapitulate    larval    guide    accompanied    gene    genetic    preliminary    suggest    functions    therapies    lack    disorder    expression    persistent    inflammation    conductance    defects    chronic    pulmonary    lung    molecules    caused    pathogens    infections    macrophages    benefit    human    morbidity    causes    fellowship    life    model    cftr    lines    deficiency    gives    innovative    models    unmet    progressive    balance    dominated    therapeutic    patients    correcting    elucidate    immune    neutrophil    zebrafish    cell    confirm    alterations    quality    dynamic    context    pathophysiology    inflammatory    combined    expectancy    active    animal    consequent    disease    severe    tractable    transmembrane    primary    microenvironment    injury    susceptibility    infection    regulator    regulating    function    mutations    limited    suitable    mucociliary    mortality    pathology    abnormalities    innate    improvement    techniques    infective    imaging    limiting    found    data    fibrosis    physiological    deficient    cf   

Project "CFZEBRA" data sheet

The following table provides information about the project.

Coordinator
THE UNIVERSITY OF SHEFFIELD 

Organization address
address: FIRTH COURT WESTERN BANK
city: SHEFFIELD
postcode: S10 2TN
website: www.shef.ac.uk

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 United Kingdom [UK]
 Total cost 195˙454 €
 EC max contribution 195˙454 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2016
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2017
 Duration (year-month-day) from 2017-06-01   to  2019-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE UNIVERSITY OF SHEFFIELD UK (SHEFFIELD) coordinator 195˙454.00

Map

 Project objective

Cystic fibrosis (CF) is a life-limiting disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Chronic pulmonary infections accompanied by persistent neutrophil-dominated inflammation result in severe progressive lung injury and are the leading causes of morbidity and mortality of CF patients. In addition to known mucociliary defects, several lines of evidence suggest primary alterations in innate immune responses contribute to CF pathology. Currently, our understanding is limited by the lack of suitable animal models that recapitulate immune abnormalities found in CF patients. To address these unmet needs, I propose to develop zebrafish larvae as a tractable animal model to investigate the role of CFTR in regulating inflammation and infection. In preliminary data, reduced zebrafish cftr expression is characterized by more inflammation and increased susceptibility to infection with CF pathogens. In this fellowship, I will use this innovative model to recapitulate aspects of the CF microenvironment. Using innovative genetic techniques combined with dynamic imaging, I will elucidate physiological functions of CFTR in innate immune pathophysiology in CF and identify new therapeutic molecules active in a CFTR-deficient context to balance infection and inflammation to benefit patients with CF. Finally, I will confirm my findings in human CF macrophages. Using larval zebrafish gives a unique insight into immune cell function in CFTR deficiency. This will help guide future therapies aimed at correcting the innate susceptibility of CF patients to infective and inflammatory lung disease, with consequent improvement of their life quality and expectancy.

 Publications

year authors and title journal last update
List of publications.
2018 A. Bernut, A. Floto, S. Renshaw
WS04.6 Balancing the immune response in cystic fibrosis: using zebrafish models of inflammation to uncover new therapeutic approaches
published pages: S8-S9, ISSN: 1569-1993, DOI: 10.1016/s1569-1993(18)30142-5
Journal of Cystic Fibrosis 17 2019-11-08
2019 Audrey Bernut, Christian Dupont, Nikolay V. Ogryzko, Aymeric Neyret, Jean-Louis Herrmann, R. Andres Floto, Stephen A. Renshaw, Laurent Kremer
CFTR Protects against Mycobacterium abscessus Infection by Fine-Tuning Host Oxidative Defenses
published pages: 1828-1840.e4, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2019.01.071
Cell Reports 26/7 2019-11-08

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