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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.

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

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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