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.
Fields of science (EuroSciVoc)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF-EF-ST - Standard EF
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2016
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
S10 2TN SHEFFIELD
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.