An interdisciplinary project investigating bicarbonate permeation across biological membranes, an understudied but physiologically important process.
Why is this research important? The CFTR channel regulates flow of chloride (Cl-) and bicarbonate (HCO3-) ions across epithelia. Recent studies have highlighted the crucial physiological role of transepithelial movement of HCO3-. HCO3- in bile and pancreatic juice is required for the breakdown and absorption of fats. In airway and gut secretions, it controls antimicrobial effects and mucus release and fluidity, affecting immune system-microbiome interactions. New CFTR-targeting drugs, developed to treat cystic fibrosis, primarily optimise Cl- conductance. Yet in some tissues CFTR mostly mediates HCO3- flow. The project will deliver chemical tools for drug development and for investigating this key, yet understudied, physiological process.
Who will you be working with? You will be part of two labs: one with expertise in supramolecular chemistry and small-molecule ion carrier testing (Cally Haynes); the other in CFTR physiology and pharmacology (Paola Vergani).
What will you be doing? You will generate a small chemical library of ionophores, using synthetic supramolecular chemistry approaches. You will then screen these molecules, and others, for selective HCO3-/Cl- transport activity in simple synthetic lipid vesicle systems. You will further characterise the most promising anionophores in a cell-based fluorescence assay, to compare ionophore- and protein-mediated transmembrane anion flow and improve the assay’s accuracy in quantifying selective HCO3- transport in a cellular context. In a second step, you will develop anionophores with diverse tissue-targeting properties.
Who are we looking for? A person enthusiastic about applying fundamental chemical knowledge and skills; curious about understanding physiological processes in depth; eager to generate tools for developing better drugs.
The EPSRC has awarded 70 fully funded projects starting in 2024/25, to be carried out at UCL. This project is in competition for funding with others. Funding will be awarded to the project that attracts the best candidate. Funding will cover: (i) 4 years fees (Home rate) (International students will receive a UCL award to cover the home/international fee difference); (ii) Maintenance stipend at the UCL EPSRC DTP enhanced rate (ie £1,000 above the UKRI London-weighted rate; this was £21,622 in 2023/24, and rises each year); (iii) Research Training Support Grant (RTSG) of £4,800. This is to cover additional costs of training eg courses, project costs, conferences, travel.
Paola Vergani ([Email Address Removed]); Cally Haynes ([Email Address Removed])