Objective The regulation of cellular ion concentrations is critical for a range of physiological processes. Malfunction of transmembrane Cl-/HCO3- antiport has been associated with cystic fibrosis and other channelopathies. Changes in pH via H+/Cl- symport cause deacidification of acidic organelles leading to cytoplasmic acidification, an early event in apoptosis. Synthetic anion transporters have been studied mainly in artificial vesicles for their ability to facilitate Cl-/HCO3- antiport and H+/Cl- symport. However, just recently it was shown that the most efficient transporters in liposome assays not always correlate to the most efficient conductors in live cell studies, most likely due to the differences between the model membrane used for the vesicle studies and the biological membranes present in cells. Therefore, a need has arisen for a systematic methodology to quantify the ability of synthetic compounds to facilitate transmembrane chloride transport in live cells. A set of prodigiosin-inspired transporter agents will be synthesized applying a newly discovered route towards 2,5-diarylpyrrole moieties. Their transmembrane anion conductor properties and pH dependency will be investigated first in unilamellar vesicle assays, to determine the transport mechanism. Further, the Ussing technique will be applied to quantify the transport efficiency in cystic fibrosis epithelial cells and to set up a systematic method for high throughput screening towards potential lead compounds in the quest against channel replacing therapies. Fluorescence in vitro cytotoxicity assays for a range of cancer cell lines will be performed and the compounds potency to introduce apoptosis will be determined. Fields of science medical and health sciencesclinical medicineoncology Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2013-CIG - Marie-Curie Action: "Career Integration Grants" Call for proposal FP7-PEOPLE-2013-CIG See other projects for this call Funding Scheme MC-CIG - Support for training and career development of researcher (CIG) Coordinator UNIVERSITY OF SOUTHAMPTON EU contribution € 50 000,00 Address Highfield SO17 1BJ Southampton United Kingdom See on map Region South East (England) Hampshire and Isle of Wight Southampton Activity type Higher or Secondary Education Establishments Administrative Contact Yan Qiao (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
