Cystic Fibrosis Bicarbonate Centre
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?
We are now recruiting! Will you contribute to RESTORING THE FIZZ?
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 email@example.com
Deadline Extended: 18/12/2022
Project one: 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
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 four: Apply 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
Project five (post already filled): Focus on airway epithelia and antimicrobial properties of secretions.
Lead academic: Isabelle Sermet-Gaudelus
Meet the Scientists