Dr L Fets
No more applications being accepted
Competition Funded PhD Project (Students Worldwide)
About the Project
Membrane transporters act as molecular gatekeepers to the cell by regulating the uptake of nutrients and ions as well as the release of waste products1. Alterations in transporter expression levels are a vital part of cancer-specific metabolic changes, since they allow the tumour to efficiently scavenge nutrients from its micro-environment in order to maintain proliferation2.
It is becoming increasingly clear that a large number of drugs ‘hijack’ plasma membrane transporters in order to enter the cell, rather than passing through the lipid bilayer3,4. This means that as well as influencing cancer metabolism, the differential expression of transporters in cancer could define the drug sensitivity profile of a tumour. To date, however, the transporters required for cell-uptake have only been identified for a handful of drugs, and the lack of understanding of drug entry into cells could partially explain the failure of many compounds in clinical trials.
We have established a computational approach to identify candidate transporters involved in the uptake of cancer therapeutic drugs. After selecting drug-transporter pairs of interest, the successful candidate will verify transporter-mediated drug uptake, looking to understand how this affects specificity, selectivity and ultimately toxicity of the compound. They will also investigate the endogenous substrates of the transporter and the role it plays in cancer metabolism, in order to determine whether metabolic dependencies can be exploited pharmacologically. While carrying out this project, the candidate will have the opportunity to learn a wide range of techniques, from cell/molecular biology and CRISPR gene-editing to mass spectrometry-based metabolomics and bioinformatics.
Funding Notes
This project is competition funded for students worldwide.
If successful the student would receive full tuition fee payment for 3.5 years as well as a tax free stipend amounting to £21,000pa paid in monthly instalments for the duration of their studentship.
Whilst Overseas Students are eligible, funding is more limited so only exceptional OS students will be considered.
References
César-Razquin, A. et al. A Call for Systematic Research on Solute Carriers. Cell 162, 478–487 (2015).
Kandasamy, P., Gyimesi, G., Kanai, Y. & Hediger, M. A. Amino acid transporters revisited: New views in health and disease. Trends in Biochemical Sciences 43, 752–789 (2018).
Fets, L. et al. MCT2 mediates concentration-dependent inhibition of glutamine metabolism by MOG. Nat Chem Biol 1–18 (2018). doi:10.1038/s41589-018-0136-y
Winter, G. E. et al. The solute carrier SLC35F2 enables YM155-mediated DNA damage toxicity. Nat Chem Biol 10, 768–773 (2014).
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