About the Project
Many cancers lose their differentiated identity and revert to a stem cell-like state. This project asks whether they do so in part by reactivating the metabolic programmes that drive growth in early development, and whether membrane transporters are important regulators of this. Transporters act as the cell's gatekeepers, controlling the uptake of nutrients and ions, the release of waste, and the movement of metabolites between organelles. In doing so, they shape the metabolic state of the cell. In early development, tightly timed changes in transporter expression help control growth, proliferation and epigenetic state. In cancer, altered transporter expression lets tumours scavenge nutrients and rewire metabolism to survive in a hostile microenvironment.
This project will investigate how developmental transporter programmes are co-opted by cancer cells to support a pro-proliferative metabolic state. Specifically, you will: i) identify transporters shared between embryonic stem cell and cancer metabolic programmes, ii) determine how these transporters reshape metabolism and cell state, iii) test their importance for tumour growth, including in vivo in the later stages of the project.
This project is a collaboration between the Fets (Drug Transport and Tumour Metabolism) and Percharde (Chromatin and Development) labs at the MRC LMS, combining expertise in cancer metabolism and early development. You will be trained in a wide range of techniques established in the lab, including cancer and embryonic stem cell culture, molecular biology, microscopy, mass spectrometry-based metabolomics and bioinformatics. We welcome applicants with a background in biochemistry, cell biology, molecular biology or a related field, and a curiosity about how metabolism controls cell fate.
To apply for this project please follow the application instructions provided on the LMS website (https://lms.mrc.ac.uk/work-and-study/studentships/lms-4-year-phd-studentships/) and submit an application form by the deadline. 'Registering your interest' below will not be considered an application.
Funding Notes
This studentship covers all tuition fees as well as a tax free stipend amounting to £26,500pa paid directly to the student in monthly instalments.
The funding is available for both Home and Overseas students.
References
- Alam S, Doherty E, Ortega-Prieto P, Arizanova J, Fets L (2023). Membrane transporters in cell physiology, cancer metabolism and drug response. Disease Models & Mechanisms. https://doi.org/10.1242/dmm.050404
- Fets L, Driscoll PC, Grimm F, et al. (2018). MCT2 mediates concentration-dependent inhibition of glutamine metabolism by MOG. Nature Chemical Biology https://doi.org/10.1038/s[contact details available in the full listing]-y
- Percharde M, Bulut-Karslioglu A, Ramalho-Santos M (2017). Hypertranscription in development, stem cells, and regeneration. Developmental Cell https://doi.org/10.1016/j.devcel.[contact details available in the full listing]
- Xie SQ, Leeke BJ, Whilding C, et al. (2022). Nucleolar-based Dux repression is essential for embryonic two-cell stage exit. Genes & Development. https://doi.org/10.1101/gad.[contact details available in the full listing]
- Intlekofer AM, Finley LWS (2019). Metabolic signatures of cancer cells and stem cells. Nature Metabolism. https://doi.org/10.1038/s[contact details available in the full listing]
