Cystic Fibrosis Bicarbonate Centre
The Cystic Fibrosis Bicarbonate Centre is a new interdisciplinary research initiative linking labs from four prestigious universities. We will focus on how bicarbonate permeation is affected in people with cystic fibrosis, in their airways and beyond.
In health, the CFTR ion channel regulates flow of chloride andÌýbicarbonateÌýions across epithelial cell layers that line airways and intestines, as well as ducts in the pancreas and in the liver. BicarbonateÌýhas antimicrobial effects in the airways and controls mucus release and fluidity in both airways and gut. BicarbonateÌýin bile and pancreatic juice is crucial for the breakdown and absorption of fats. In people with cystic fibrosis (CF) CFTR is missing or defective. New CFTR-targeting modulator drugs have been developed, but they primarily optimise CFTR’s chloride conductance. There is now evidence that, at least in bile ducts, current therapies restore chloride but notÌýbicarbonateÌý´Ú±ô´Ç·É.
This interdisciplinary centre is formed by an international team of researchers with different expertise, coming together to investigate CFTR-dependentÌýbicarbonateÌý²õ±ð³¦°ù±ð³Ù¾±´Ç²Ô.
FiveÌýPhD students, supported by fiveÌýdifferent labs, each one exploiting/developing cutting-edge technologies, will join forces to address these questions:
- How isÌýbicarbonateÌýflow controlled in different organs?Ìý
- How do CFTR mutations and new CFTR modulator drugs affect it?Ìý
- How does its absence contribute to CF symptoms?Ìý
- Most important, how can we improve modulator therapy to better rescue normal transepithelialÌýHCO3Ìýfluxes, and restore the fizz for people with CF?Ìý
Ìý
Project one:ÌýDevelopment of high-content fluorescence assays to rapidly monitor CFTR-mediated bicarbonate flow - how do CFTR mutations and modulator drugs affect it?
Lead academic: Paola VerganiÌý
Project two: Investigating the rescue of cystic fibrosis-causing mutations by CFTR modulators with patch-clamp electrophysiology.
Lead academic:ÌýDavid SheppardÌý
ProjectÌýthree: Work on stem-cell derived epithelia (2D organoids mimicking gut, pancreas and liver ducts), to investigate transcriptome andÌýtransepithelial anion fluxes.
Lead academic: Marcel Bijvelds
Project four:ÌýApply nanosensing technology (SICM) to examine the impact of CFTR HCO3-Ìýtransport in controlling the volume, pH and viscoelasticity of cell secretions and the importance of this for health.
Lead academic: Guy MossÌý
Project five:ÌýFocus on airway epithelia and antimicrobial properties of secretions.
Lead academic:ÌýIsabelle Sermet-GaudelusÌý
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Meet the Scientists
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Institut Necker Enfants Malades
Graduate student from the Indian Institute of Science Education and Research devoted to biochemistry and proteomics.
Bristol University Pharmacology graduate and patch-clamp eletrophysiologist.
×î×¼µÄÁùºÏ²ÊÂÛ̳ Pharmacology graduate interested in channels and rheology of epithelial secretions.
Biomedical Sciences graduate from ×î×¼µÄÁùºÏ²ÊÂÛ̳ and Imperial with a keen interest in therapy inovation for complex diseases.
Eötvös Loránd University (ELTE) graduate with an interest in genetic modification.
Hugo de Jonge, in memoriam
Hugo brought us together, excited by preliminary data from his lab, and first suggested a project which wasÌý"so close to [his] heart". It was with deep sorrow that we found out the illness had taken him away prematurely.Ìý We will miss him: his almost infinite knowledge of all that is epithelial, his attention to detail, his scientific acuity and, most of all, his friendship.