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SELF-FUNDING MSc BY RESEARCH PROJECT: Cystic fibrosis: restoring ion transport with small molecules


School of Physiology and Pharmacology

Bristol United Kingdom Pharmacology

About the Project

Cystic fibrosis (CF) is caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR), a unique ATP-binding cassette transporter that functions as an ATP-gated anion channel, playing a pivotal role in salt and water movement across epithelial tissues (1). To date more than 2,000 mutations have been identified in the CFTR gene, but most are very rare and not all cause disease (1, 2). The most common cause of CF, the F508del mutation, disrupts CFTR transport to and stability at the plasma membrane and interferes with channel gating (2). To overcome these defects, small molecules have been developed called CFTR correctors and potentiators, which rescue the plasma membrane expression and function of F508del-CFTR (3). Other small molecules restore ion transport to CF cells by activating different anion channels expressed in these cells or functioning as artificial anion channels and transporters (4). An MSc by Research project with our group would explore how rare CF mutations cause CFTR dysfunction and small molecules restore ion transport to CF cells by rescuing or bypassing faulty CFTR proteins (5-8).


Funding Notes

This project is for students who can fund the project themselves; there is no financial support.
Please apply to the Faculty of Life Sciences, School of Physiology and Pharmacology, selecting the programme 'MSc by Research'
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References

1. Ratjen F et al. Nat Rev Dis Primers. 2015; 1:15010.
2. Veit G et al. Mol Biol Cell. 2016; 27:424-33.
3. Hanrahan JW et al. Curr Opin Pharmacol. 2017; 34:105-111.
4. Li H et al. Curr Opin Pharmacol. 2017; 34:91-97.
5. Kirchner S et al. PLoS Biol. 2017; 15:e2000779.
6. Meng X et al. J Biol Chem. 2017; 292:3706-3719.
7. Liu J et al. Br J Pharmacol. 2018; 175:1017-1038.
8. Li H et al. Nat Chem. 2016; 8:24-32.

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