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How mutations in the "Cystic Fibrosis Transmembrane Conductance Regulator" gene alter the immune system in Cystic Fibrosis patients

Carlsbergfondets internationaliseringsstipendier

What

The aim of this project is to study the impaired response from the immune system in Cystic Fibrosis patients. Especially the neutrophils, that are first to arrive in infections of the lung, will be studied. The theory is that Cystic Fibrosis patients have an altered immune system that lacks the eliciting effects and thereby help sustain the infections and inflammations in the lungs, because of lack of CFTR function.

Why

This will be a whole new aspect of an earlier considered well-known disease and will change the way we treat and approach Cystic Fibrosis. If the immune system can be altered by mutations in CFTR, it may be that mutations in other non-immunological genes will also change the immune system. New treatments and diagnostics could then be considered on many known genetic diseases and thereby bring in a new therapeutic approach. This will not only be a study on Cystic Fibrosis, but a new method-study on how to bring in research on the immune system, and here by using the disease model Cystic Fibrosis.

How

CFTR expression and alteration in the elicited immune response in cultured cell lines with the CF genotype or primary cells from CF patients and CF mice will be studied. Primary cells to be used are neutrophils from bronchoalveolar lavage fluid of CF patients. Expression levels of cytokines will be detected using quantitative PCR for mRNA and a Luminex instrument to assess cytokine proteins. Epigenetic modifications will be detected using chromatin immunoprecipitation followed by next generation sequencing. Primary airway epithelial cells from CF patients will be cultured with non-CF neutrophils and the vice-versa and the possible changes in the cytokine level detected, which will provide insight into the relative contribution of CFTR's absence from each cell type.

SSR

Research will be done at the Research Institute for Children's Health, which not only goes out to Cystic Fibrosis patients, but research done here can be used for many other diseases concerning the health of children.