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

This interdisciplinary centre is formed by an international team of researchers with different expertise, coming together to investigate CFTR-dependent bicarbonate secretion.

Four PhD students, and a PostDoctoral researcher, supported by five different labs, each one exploiting/developing cutting-edge technologies, will join forces to address these questions:

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

PhD Opportunities

We are now recruiting! Will you contribute to RESTORING THE FIZZ?

Four fully funded interdisciplinary PhD Studentships will be available as part of this Strategic Research Centre, co-funded by the Cystic Fibrosis Trust (UK) and the Cystic Fibrosis Foundation (USA).

There will be one PhD studentship for each of the four projects listed below. 

Applications (one PDF including a CV with contact details for two referees, a two - three paragraph statement explaining your interest in the project and what you feel you will bring to the role, and an official University transcript) should be sent to biosciences.pgr.admin@ucl.ac.uk

Deadline Extended: 18/12/2022
 

Project oneDevelopment 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 

YFP-CFTR and cytosolic pHuji will be coexpressed from a bicistronic plasmid in HEK293 cells. Quenching of YFP fluorescence upon addition of extracellular I- informs on ion channel function. Membrane proximity (ratio of average YFP-CFTR fluorescence within 5 pixels from cell borders over average pHuji fluorescence throughout the cell) informs on the number of channels at the membrane. The pH sensitive pHuji fluorescence will inform on cytosolic pH.


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


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


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

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 (post already filled): Focus on airway epithelia and antimicrobial properties of secretions.
Lead academic: Isabelle Sermet-Gaudelus 

 

Meet the Scientists

 

Paolo Vergani
David Sheppard

David Sheppard

Bristol University

M.J.C. Bijvelds

Marcel Bijvelds

Erasmus Medical Centre

guy moss

Guy Moss

UCL

Isabelle Sermet Gaudelus

Isabelle Sermet Gaudelus

Institut Necker Enfants Malades

Hugo de Jonge, in memoriam

jonge-hugo-de
Hugo brought us together, excited by preliminary data from his lab, and first suggested a project which was "so close to [his] heart". It was with deep sorrow that we found out the illness had taken him away prematurely.  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.