• University of Southampton Featured PhD Programmes
  • Staffordshire University Featured PhD Programmes
  • Aberdeen University Featured PhD Programmes
  • FindA University Ltd Featured PhD Programmes
  • University of Pennsylvania Featured PhD Programmes
  • University of Cambridge Featured PhD Programmes
University of York Featured PhD Programmes
University of Liverpool Featured PhD Programmes
University of Leeds Featured PhD Programmes
Peter MacCallum Cancer Centre Featured PhD Programmes
University of Reading Featured PhD Programmes

The role of Transmembrane Helix 3 in Drug Selectivity in ABCG2

This project is no longer listed in the FindAPhD
database and may not be available.

Click here to search the FindAPhD database
for PhD studentship opportunities
  • Full or part time
    Dr Kerr
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

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 scant information regarding regions on the protein responsible for drug and inhibitor interaction [1,2]. This project aims to address these questions.
In terms of drug binding it is known that 2 residues in the lower (cytoplasmic) region of TM helix 3 in ABCG2 are important in drug recognition. In the current proposal we would examine ABCG2 drug binding as follows:

i) Mutation of other residues in TM helix 3.
ii) Further characterization of residues of importance in TM helix 3

In part i) we would make mutations through the length of TM3 and then produce stable cell lines expressing these mutant forms. We would then confirm membrane localization of mutants, and then probe function using two routine functional assays (fluorescence based). This would enable us to identify residues that are possible part of a drug binding site on the protein, or residues which contribute to the known allostery between drug binding and ATP hydrolysis.

In part ii) we would take mutants of interest and examine them in an alternative experimental system that allows us to determine how ABCG2:drug interactions are communicated to the ATP hydrolysis of this pump. This would enable us to develop a molecular understanding of drug transport by this important multidrug pump.

Through the project the student would receive training in a number of different techniques including molecular biology, cell culture, fluorescence-based assays, confocal microscopy, 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

Home and EU applicants should contact the supervisor to determine the current funding status for this project. International applicants should visit our 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

Wong, K., Ma, J., Rothnie, A., Biggin, P. C., and Kerr, I. D. (2014) Towards understanding promiscuity in multidrug efflux pumps, Trends in biochemical sciences 39, 8-16.
Kerr, I. D., Haider, A. J., and Gelissen, I. C. (2011) The ABCG family of membrane-associated transporters: you don't have to be big to be mighty, Br J Pharmacol 164, 1767-1779

How good is research at University of Nottingham in Biological Sciences?

FTE Category A staff submitted: 90.86

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities
Share this page:

Cookie Policy    X