4 Fully funded interdisciplinary PhD Studentships

Available in a new Strategic Research Centre (SRC), co-funded by the Cystic Fibrosis Trust (UK) and the Cystic Fibrosis Foundation (USA).

Will you contribute to RESTORING THE FIZZ?

In health, the CFTR ion channel regulates flow of Cl^- and HCO₃^- ions across the epithelial layers that line airways, intestine, ducts in the pancreas and in the liver. HCO₃^- has antimicrobial effects in the airways and has been shown to control mucus release and fluidity in both airways and gut. HCO₃^- 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 Cl^- conductance. There is evidence that, at least in bile ducts, current therapies restore Cl^- but not HCO₃^- flow.

This interdisciplinary SRC will bring together researchers with different expertise to investigate CFTR-dependent HCO₃^- secretion. 4 PhD students (and a PostDoctoral researcher), supported by different labs, each one exploiting/developing cutting-edge technologies, will work together to address these questions:

• How is HCO₃^- 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?

Visit our website for more information and to apply

Available Projects

Project 1 (UCL)
Deadline Extended!

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 border with respect to average pHuji fluorescence throughout the cell) informs on channel density at the membrane. The pH sensitive pHuji fluorescence will inform on cytosolic pH.

Project 2 (Bristol University)

Project 3 (Erasmus Medical Centre, Netherlands).

Project 4 (UCL)
Deadline Extended!

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.

(The centre will also include a PostDoctoral researcher working at Institut Necker Enfants Malades in Paris, France, who will be focusing on airway epithelia and antimicrobial properties of secretions.)

As well as being part of the SRC team, the PhD students will each be integrated within the Doctoral Schools at their Institution. Finally, the students themselves will be involved in communicating their research to the CF community of patients, carers and clinicians.