Resistance to chemotherapy causes tens of thousands of cancer deaths in Europe each year. One protein, the multidrug resistance P-glycoprotein encoded by the MDR1 gene, can confer multidrug resistance on cells and tumours, acting as an ATP-dependent transporter to pump drugs out of cells. This project will contribute to our understanding of the structure and function of P-glycoprotein. A detailed understanding of the mechanisms by which this transporter acts is not only of fundamenal scientific interest and importance, but may contribute to the develpoment of improved antitumour agents.
The project will involve site-directed mutagenesis to introduce single cysteine residues into specific sites on P-glycoprotein and labelling these residues with fluorescent or spin labels. A biophysical study of these labelled proteins, together with electron microscope imaging techniques, will allow a detailed model of the structure and function of this protein to be developed. Necessary preliminary work and method development for this project have already been completed and the project will provide training in a range of molecular biology, protein chemistry and biophysical techniques.