Strategic Research Centre: F508del

Professor David Sheppard and his team will investigate the effect of the F508del mutation, the most common cystic-fibrosis causing mutation, on the CFTR protein.

The CFTR protein channel forms a gated pathway that regulates the movement of sodium and chloride ions across the cell membrane. A defective protein or absence of this protein is the root cause of cystic fibrosis. The F508del defect prevents the CFTR from assembling correctly within the cell or causes it to be fragile, which means that it does not transport chloride properly and quickly falls apart. F508del is the most common of the more-than 1,400 CF mutations. Around 90% of the UK CF population carries at least one copy, and around 50% carries two.

Led by Professor David Sheppard at the University of Bristol, this Strategic Research Centre (SRC) aims to investigate when and where inside duct-lining cells the CFTR develops a structure capable of forming a gated pathway for chloride movement. The team will:

• Investigate the structure of the CFTR and how it is affected by the F508del defect; and
• Search for chemicals that repair all the faults in CFTR caused by the F508del defect, so that the CFTR is correctly made and delivered to the cell border to form a stable gated pathway for chloride movement.

The study has the potential to lead to long-term improvements in the longevity and quality of life for people with cystic fibrosis by restoring function to the defective CFTR.

Lead Principal Investigator (PI): Professor David Sheppard (University of Bristol)

Co-PIs:

Professor Frédéric Becq (Université de Poitiers)

Professor Ineke Braakman (Utrecht University)

Professor Robert C Ford (The University of Manchester)

Dr Paola Vergani (University College London)

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