Dr Noor Gammoh, University of Edinburgh & Dr Natividad Gomez-Roman, University of Strathclyde
Glioblastoma (GBM) is the most common and devastating form of brain cancer. Understanding survival pathways that drive GBM resistance to therapy is important for the development of novel and effective therapeutic approaches. One such pathway is autophagy, a lysosomal degradation mechanism required for the clearance of a wide range of cellular cargo and for maintaining cellular homeostasis. Our lab has previously shown that autophagy is crucial for GBM development and survival. Although there is compelling genetic evidence suggesting that autophagy promotes the survival and resistance to treatment of cancer cells, its therapeutic targeting remains challenging due to the lack of effective and non-toxic inhibitors.
Unpublished findings from our lab demonstrate that the availability of fatty acids (FAs) is important for GBM cell survival. We observed that targeting FA synthesis with small molecules enhanced cell death in GBM cells treated with temozolomide (TMZ), a chemotherapeutic agent commonly used in the clinic. Mechanistically, suppressing FA synthesis inhibited autophagy and elicited an endoplasmic reticulum (ER) stress response, suggesting that cellular homeostasis is compromised. Importantly, unlike current therapeutic strategies that focus on inhibiting lysosomal degradation, targeting FA synthesis suppressed autophagy at early stages, potentially indicating lower toxicity in normal cells. Altogether, these findings highlight an important crosstalk between FA availability and cellular homeostasis in GBM.
This project aims to further understand the underlying molecular mechanisms by which FA availability influences cell survival and investigate the use of FA synthase inhibitors (used as appetite suppressants) in compromising GBM growth. The project combines basic cell biology approaches with animal models and drug/radiation treatments. More specifically, the project aims to:
- Characterise the molecular changes resulting from modulating lipid synthesis which inhibit autophagy and trigger ER stress in cells (Edinburgh). Methods include: high-resolution imaging, MS profiling of cells, CRISPR/Cas9-gene editing in glioma stem cells.
- Evaluate the effects of altering lipid synthesis and availability on the sensitivity of cultured GBM cells to standard of care treatment (Strathclyde). Methods include: 3D cell culture, FA synthase inhibitors, radiation or chemotherapy (TMZ) treatment in patient-derived GBM cell lines.
- Investigate whether targeting lipid synthesis and ER stress activation can suppress GBM growth using mouse model (Edinburgh). Methods include: intracranial injections of GBM cells.
Overall, findings from this project will provide a wide range of training opportunities to the PhD candidate and may reveal potential translational opportunities in future studies.
For further information on the project or informal enquiries, please contact Dr Noor Gammoh, This email address is being protected from spambots. You need JavaScript enabled to view it.
To place an application, please visit this site at the University of Edinburgh.
When submitting your application please make sure that you have also completed your application to the Windsor Fellowship and please upload the completed recruitment form.
Duration: 4 years, starting October 2026
Closing Date: 24th November 2025
Interview for this position will take place in January 2026
Lab Websites
Dr Noor Gammoh - Brain Cancer Survival Pathway
References
Simpson JE, Muir MT, Lee M, Naughton C, Gilbert N, Pollard SM, Gammoh N (2024) Autophagy regulates PDGFRA-dependent brain tumour development by modulating oncogenic signalling. Developmental Cell 59(2):228-243.e7
Makar AN, Boraman A, Mosen P, Simpson JE, Marques J, Michelberger T, Aitken S, Wheeler AP, Winter D, Kriegsheim A, Gammoh N (2024) The V-ATPase complex component RNAseK is required for lysosomal hydrolase delivery and autophagosome degradation. Nature Communications 15(1):7743
Debnath J*, Gammoh N*, Ryan KM* (2023) Autophagy and autophagy-related pathways in cancer. Nature Reviews Molecular Cell Biology 2:1-16
Jackson MR, Richards, RR, Oladipupo, A-B O, Chahal, SK, Caragher, S, Chalmers AJ, Gomez-Roman N (2023) ClonoScreen3D – A Novel 3-Dimensional Clonogenic Screening Platform for Identification of Radiosensitizers for Glioblastoma. International Journal of Radiation Oncology, Biology, Physics, 120(1): 162-177