Understanding structure and drug binding in the multidrug pump ABCG2
Fact file
| Duration |
Three to four years full-time |
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| Eligibility |
Self-funded; Home, EU or International Students |
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| Supervisor(s) |
Dr Ian Kerr
Dr Robert Layfield
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| Application deadline |
No deadline |
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About the project
ABCG2 is one of three human ATP binding cassette transporters that are functionally capable of exporting a diverse range of substrates from cells. The physiological consequence of ABCG2 multidrug transport activity in leukaemia, and some solid tumours is the acquisition of cancer multidrug resistance. The molecular basis for drug resistance is currently unknown, and we have limited information regarding regions on the protein responsible for drug and inhibitor interaction. This project aims to address these questions.
Our two aims in this project are
i) Purify ABCG2 from over-expressing cell lines to enable quantitative determination of transporter:substrate interaction using biophysical techniques
ii) Aim to identify the regions of the transporter responsible for drug binding by mutagenesis and functional activity
Through the project the student would receive training in a number of different techniques including molecular biology, cell culture, fluorescence-based assays, confocal microscopy, molecular modelling, membrane and protein biochemistry. The student would also receive training in data analysis, reading the scientific literature, and scientific writing and presentation. The student would contribute to a vibrant research group, and would make presentations to the group and the wider scientific community.
Funding notes
This project is available to self-funded students. Home applicants should contact the supervisor to determine the current funding status for this project. EU applicants should visit the Graduate School webpages for information on specific EU scholarships. International applicants should visit our International Research Scholarships page for information regarding fees and funding at the University.
References
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Cox, M. H., Kapoor, P., Briggs, D. A., and Kerr, I. D. (2018) Residues contributing to drug transport by ABCG2 are localised to multiple drug-binding pockets, Biochem J 475, 1553-1567
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Wong, K., Briddon, S. J., Holliday, N. D., and Kerr, I. D. (2016) Plasma membrane dynamics and tetrameric organisation of ABCG2 transporters in mammalian cells revealed by single particle imaging techniques, Biochim Biophys Acta 1863, 19-29.
- Horsey, A. J., Cox, M. H., Sarwat, S., and Kerr, I. D. (2016) The multidrug transporter ABCG2: still more questions than answers, Biochem Soc Trans 44, 824-830.
See this project on FindaPhD
Understanding structure and drug binding in the multidrug pump ABCG2