JAMT: Understanding substrate-selective TORC1 signalling for tackling cancer

About the Project

Uncontrolled cell growth is a hallmark of cancer. Efforts have been made to restrict tumour growth by pharmacologically inhibiting a master driver of cell growth, the Target of Rapamycin Complex 1 (TORC1/mTORC1) kinase complex. However, the limited success of this approach was explained by recent evidence showing that inhibiting TORC1 activity towards some substrates actually benefits cancer cells. Specifically, inhibiting TORC1-mediated phosphorylation of the TFEB transcription factor promotes invasion of triple-negative breast cancer cells [PMID: 39729986]. Therefore, effective treatment of invasive/metastatic cancer requires redesign of the therapeutic strategy to inhibit TORC1 activity towards its canonical substrates (such as S6K and 4EBP1, regulators of global protein synthesis), while maintaining its activity towards TFEB.

This strategy reflects a recent paradigm shift in the TORC1 research field, pioneered by my group, in understanding that TORC1 can operate in a substrate-selective manner. For both yeast and mammalian cells, evidence has emerged for functionally distinct subcellular TORC1 pools, lysosomal and non-lysosomal [PMID: 30527664][PMID: 39385049]. Each TORC1 pool phosphorylates distinct sets of substrates under control of pool-specific upstream regulators, including G protein-coupled receptors (GPCRs) [doi.org/10.1101/2024.09.18.613687].

This project will elucidate the molecular mechanisms of pool-specific TORC1 regulation utilizing our unique yeast system, in which the activities of the two TORC1 pools can be separately monitored and manipulated. We will then apply the findings to breast cancer cells to examine if pool-specific TORC1 manipulation can suppress cancer growth without promoting invasion. This project potentially revolutionizes our therapeutic approach to cancer by exploiting substrate-selective TORC1 signalling.

The student will benefit from the interdisciplinary supervisory team and be trained on skills and knowledge in yeast genetics, image analysis, and cancer cell biology, which are widely valued in academia, food/biotechnology, and pharmaceutical industries.

Informal enquiries are encouraged, please contact Dr Riko Hatakeyama (riko.hatakeyama@abdn.ac.uk) for further information.

ELIGIBILITY:

Applicants should hold a minimum of a 2:1 UK Honours degree (or international equivalent) in a relevant subject. Those with a 2:2 UK Honours degree (or international equivalent) may be considered, provided they have (or are expected to achieve) a Distinction or Commendation at master’s level.

We actively encourage applications from diverse career paths and backgrounds and across all sections of the community, regardless of age, disability, ethnicity, gender, gender expression, sexual orientation and transgender status, amongst other protected characteristics.

Application Procedure

Important note: This project is open only to applicants eligible for the Home/UK fee rate. This includes EU students who hold settled or pre-settled status and meet the relevant residency criteria.

To apply, please submit the following documents via email to smmsn-pgrenquiries@abdn.ac.uk

• A cover letter addressed to the supervisor of the project you're applying for.
• An up-to-date CV detailing your academic qualifications, employment history, and any other relevant experience. Please ensure your current permanent address is clearly stated, as this will be used to determine your fee status.
• Clear copies of your degree certificates and transcripts (if available).
• Evidence of settled or pre-settled status (if applicable).

Please send your application with documents attached as a single email with the subject line: "JAMT Riko Hatakeyama - [Your Name]"

The deadline for applications is 23:59 GMT on 14th June 2026. Please note that incomplete applications will not be considered.

For any enquiries regarding your application or the application process, please contact smmsn-pgrenquiries@abdn.ac.uk

Funding Notes

This competitively funded research project is one of six opportunities currently advertised by the University of Aberdeen, seeking exceptional candidates. The James Alexander Mearns Trust (JAMT) will fund the project that attracts the most promising applicant.

The fully funded position includes UK/Home tuition fees, research costs, and a tax-free doctoral stipend of £21,805 for the 2026/2027 academic year (increases annually). The project is expected to start in October 2026.

References

• Atkinson SJ, Negoita F, Ritchie WV, Thompson K, Sakamoto K, Thompson D, Hislop JN, Hatakeyama R. (2024)
  Substrate-specific regulation of the mTORC1 pathway by G protein-coupled receptors.
  BioRxiv. doi: https://www.biorxiv.org/content/10.1101/2024.09.18.613687.
• Muneshige K and Hatakeyama R. (2025)
  Vacuoles provide the source membrane for TORC1-containing signaling endosomes.
  Journal of Cell Biology. 224 (5): e202407021.
• Hatakeyama R, Péli-Gulli MP, Hu Z, Jaquenoud M, Garcia Osuna GM, Sardu A, Dengjel J, De Virgilio C. (2019)
  Spatially distinct pools of TORC1 balance protein homeostasis.
  Molecular Cell. 73:325-338.