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 and听bicarbonate听ions across epithelial cell layers that line airways and intestines, as well as ducts in the pancreas and in the liver. Bicarbonate听has antimicrobial effects in the airways and controls mucus release and fluidity in both airways and gut. Bicarbonate听in 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鈥檚 chloride conductance. There is now evidence that, at least in bile ducts, current therapies restore chloride but not听bicarbonate听蹿濒辞飞.

This interdisciplinary centre is formed by an international team of researchers with different expertise, coming together to investigate CFTR-dependent听bicarbonate听蝉别肠谤别迟颈辞苍.

Five听PhD students, supported by five听different labs, each one exploiting/developing cutting-edge technologies, will join forces to address these questions:

How is听bicarbonate听flow controlled in different organs?听
How do CFTR mutations and new CFTR modulator drugs affect it?听
How does its absence contribute to CF symptoms?听
Most important, how can we improve modulator therapy to better rescue normal transepithelial听HCO₃听fluxes, and restore the fizz for people with CF?听

听

Project one:听Development of high-content fluorescence assays to rapidly monitor CFTR-mediated bicarbonate flow - how do CFTR mutations and modulator drugs affect it?
Lead academic: Paola Vergani听

Project one details

Project two: Investigating the rescue of cystic fibrosis-causing mutations by CFTR modulators with patch-clamp electrophysiology.
Lead academic:听David Sheppard听

Project two details

Project听three: Work on stem-cell derived epithelia (2D organoids mimicking gut, pancreas and liver ducts), to investigate transcriptome and听transepithelial anion fluxes.
Lead academic: Marcel Bijvelds

Project three details

Project four:听Apply nanosensing technology (SICM) to examine the impact of CFTR HCO₃^-听transport in controlling the volume, pH and viscoelasticity of cell secretions and the importance of this for health.
Lead academic: Guy Moss听

Project four details

Experimental approaches exploiting monolayers derived from organoids. Experiments to measure single-channel gating and permeation, transepithelial Cl^- and HCO₃^- currents, hydration and spinnability of luminal secretions (as well as expression studies and pHstat titration) will be run using common experimental conditions, to facilitate reaching integrated, strong interpretations.

Project five:听Focus on airway epithelia and antimicrobial properties of secretions.
Lead academic:听Isabelle Sermet-Gaudelus听

听

Meet the Scientists

听

乱伦秀

Bristol University

Erasmus Medical Centre

Guy Moss

乱伦秀

Institut Necker Enfants Malades

Lunavath Jyosthna Naik

Graduate student from the Indian Institute of Science Education and Research devoted to biochemistry and proteomics.

James Charlick

Bristol University Pharmacology graduate and patch-clamp eletrophysiologist.

Saidi Li

乱伦秀 Pharmacology graduate interested in channels and rheology of epithelial secretions.

Yashoda Jayal

Biomedical Sciences graduate from 乱伦秀 and Imperial with a keen interest in therapy inovation for complex diseases.

Erdene Baigal

E枚tv枚s Lor谩nd 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 was听"so close to [his] heart". It was with deep sorrow that we found out the illness had taken him away prematurely.听 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.