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Understanding structure and drug binding in the multidrug pump ABCG2


School of Life Sciences

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Dr I Kerr , Dr R Layfield Applications accepted all year round Self-Funded PhD Students Only

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.


The University of Nottingham is one of the world’s most respected research-intensive universities, ranked 8th in the UK for research power (REF 2014). Students studying in the School of Life Sciences will have the opportunity to thrive in a vibrant, multidisciplinary environment, with expert supervision from leaders in their field, state-of-the-art facilities and strong links with industry. Students are closely monitored in terms of their personal and professional progression throughout their study period and are assigned academic mentors in addition to their supervisory team. The School provides structured training as a fundamental part of postgraduate personal development and our training programme enables students to develop skills across the four domains of the Vitae Researcher Development Framework (RDF). During their studies, students will also have the opportunity to attend and present at conferences around the world. The School puts strong emphasis on the promotion of postgraduate research with a 2-day annual PhD research symposium attended by all students, plus academic staff and invited speakers.

Funding Notes

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 http://www.nottingham.ac.uk/graduateschool/index.aspx. International applicants should visit our International Research Scholarships page for information regarding fees and funding at the University http://www.nottingham.ac.uk/studywithus/international-applicants/scholarships-fees-and-finance/scholarships/index.aspx.

References

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

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.
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