Background
Cancer remains a major global health challenge, with lung, breast, and colorectal cancers accounting for nearly one-third of the 20 million new cases worldwide in 2022 (Globocan 2022). Solid tumours often experience poor vascularization, creating hypoxic microenvironments that reshape cell metabolism, angiogenesis, invasion, immune evasion, and therapy resistance. These adaptive responses are mainly orchestrated by hypoxia-inducible factors (HIFs), such as HIF-1α, which rewire gene expression to support tumor survival and progression. A key adaptive process triggered by hypoxic conditions is mitophagy, the selective autophagic degradation of damaged mitochondria. Mitophagy is essential to maintain redox balance and meet metabolic demands of cancer cells, but its role in cancer is highly context dependent. During early tumorigenesis, mitophagy can act as a tumor-suppressive mechanism by limiting the accumulation of reactive oxygen species inhibiting tumor growth. In contrast, tumors at advanced stage, particularly with hypoxic niches, it often becomes pro-survival, maintaining ATP and limiting oxidative stress, thereby contributing to resistance to radiation and chemotherapy. This duality makes the hypoxia–mitophagy axis a fascinating therapeutic target as its inhibition may sensitize resistant tumors, while its overactivation could trigger mitochondrial failure and cell death. Therefore, understanding the regulation of mitophagy in cancer, and the identification of novel regulators of this process, is essential to clarify the mechanisms by which cancer cells exploit mitophagy under hypoxia.
Goal of the project
In order to identify novel regulators of mitophagy under hypoxia conditions, we previously performed an siRNA screen of candidates obtained from transcriptomic and proteomic analyses. Collectively, this approach revealed several potential regulators of mitophagy. As part of the project, the master student will investigate the molecular mechanism and physiological role of a selected candidate in hypoxia-induced mitophagy, working closely within the research team.
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Methods
The student will learn a wide range of molecular and cell biology methods, including mammalian cell culture, DNA/siRNA cell transfection, molecular cloning and CRISPR/Cas9 genome editing, western blotting, RNA and DNA isolation, RT-qPCR, confocal microscopy, live-cell imaging among other techniques.
About the student
We are seeking a highly motivated, proactive, and self-driven full-time student with background in cell biology to join our laboratory. The candidate will gradually take responsibility for planning and managing their own work, developing into an independent laboratory researcher while receiving continuous guidance on the project plan and support from the supervisor and co-supervisor. Additionally, the student should engage with relevant literature, to gain a thorough understanding of the project, and actively present their work in meetings to strengthen communication skills and prepare for the Master’s thesis examination.
About us
The project will be carried out in the Autophagy Research Group, led by Professor Anne Simonsen, at the Department of Molecular Cell Biology, Institute for Cancer Research. We offer an international and dynamic research environment, with a diverse team of scientists skilled in a wide range of techniques. You will be supported in developing the tools and expertise necessary to pursue a PhD, while receiving proper recognition for your contributions, with the goal of publishing in high-quality international journals. The project also provides opportunities to enhance dissemination skills, foster collaborative learning, and actively engage in an inspiring scientific community. You can read more about our group on this website: https://www.ous-research.no/simonsen.
The group is also part of CanCell – Center for Cancer Cell Reprogramming, a Center of Excellence (SFF) and ARCTiC (Autophagy Research Center Targeting Cancer), both offering a great multidisciplinary and stimulating scientific environment.
References
- Spinelli, J. B. & Haigis, M. C. The multifaceted contributions of mitochondria to cellular metabolism. Nat Cell Biol 20, 745-754 (2018).
- Vyas, S., Zaganjor, E. & Haigis, M. C. Mitochondria and Cancer. Cell 166, 555-566 (2016).
- Ng, M. Y. W., Wai, T. & Simonsen, A. Quality control of the mitochondrion. Dev Cell 56, 881-905 (2021).
- Trachsel-Moncho L, Veroni C, Mathai BJ, Lapao A, Singh S, Asp NT, Schultz SW, Pankiv S, Simonsen A. SNX10 functions as a modulator of piecemeal mitophagy and mitochondrial bioenergetics. J Cell Biol. 2025 May 5;224(5):e202404009.
- Munson MJ, Mathai BJ, Ng MYW, Trachsel-Moncho L, de la Ballina LR, Schultz SW, Aman Y, Lystad AH, Singh S, Singh S, Wesche J, Fang EF, Simonsen A. GAK and PRKCD are positive regulators of PRKN-independent mitophagy. Nat Commun. 2021 Oct 20;12(1):6101.