Background
Human cells are constantly exposed to mechanical forces, both in normal physiology and in disease. For example, cells experience mechanical stress during migration through confined spaces, muscle contraction, tumor growth, and immune cell infiltration into tissues. Cells actively sense these forces and can respond by changing nuclear organization and gene expression.
Emerging evidence, including our previous work, indicates that mechanical stress can alter chromatin architecture and epigenetic regulation1–3. However, the mechanisms by which cells “translate” mechanical forces into specific chromatin changes remain poorly understood. In particular, it is unclear how heterochromatin-associated proteins such as HP1 contribute to this response.
Understanding how mechanical forces shape chromatin is highly relevant in cancer, where tumor growth and altered tissue stiffness change the mechanical environment of cells. Insights from this project may therefore inform how mechanical cues influence tumor progression, therapy responses, and immune cell function.
Project
This master project will investigate how mechanical stress affects heterochromatin and epigenetic regulation, with a focus on HP1 and related chromatin regulators. The project builds on methodology established in the lab: human cell lines, mechanical stress assays, and CRISPR/Cas9-based tagging of endogenous proteins to visualize proteins and use degron systems.
You will learn and apply state-of-the-art epigenomic methods (Cut&Run) to measure how chromatin state changes in response to controlled mechanical stress. You will then explore the role of HP1 proteins in this response by altering protein expression levels and properties. Depending on progress and your interests, you will also be able to learn RNA-Seq and/or Hi-C data analysis to link mechanical stress to gene expression and 3D genome organization. This work will be integrated with a bigger project that includes live-cell imaging of nuclear and chromatin organization.
Overall, this project combines mechanobiology, chromatin biology, and super-resolution imaging to uncover how mechanical forces influence chromatin and gene regulation, with clear relevance for cancer and immune cell biology.
Methods and skills
You will gain experience with:
- Mammalian cell culture: Handling and maintenance of human cell lines
- CRISPR/Cas9 knock-in generation: Design of CRISPR strategies, validation of knock-in cell lines using molecular biology techniques, FACS sorting, fluorescence microscopy, and genotyping.
- Epigenomic and transcriptomic methods: Cut&Run to profile selected epigenetic marks and chromatin-associated proteins, including library preparation and quality control.
- Bioinformatic analysis of sequencing data: Alignment, peak calling, differential analysis.
- Integration with RNA-Seq and Hi-C workflows to study transcriptional and 3D genome responses to mechanical stress.
- Live-cell and super-resolution microscopy as a supporting technique.
About the group
We are an interdisciplinary research group combining experimental cell and molecular biology with computational analysis. You will work within an ongoing project on mechanobiology and chromatin. As a master's student, you will receive supervision in both experimental techniques and data analysis, and contribute to understanding how mechanical forces regulate chromatin organization and gene expression in health- and disease-related contexts, such as cancer.
Supervisors
Cinzia Anita Maria Progida, Jonas Paulsen, Evdokiia Potolitsyna
Contact person
If you are interested, please contact Evdokiia Potolitsyna (evdokiip@uio.no).
References
1. Oshagi, S., Hovet, O., Halaburkova, A., Progida, C. & Paulsen, J. The 3D nuclear position and compartmentalization of genes prime their response to mechano-confinement. bioRxiv 2025.11.06.686901 (2025) doi:10.1101/2025.11.06.686901.
2. Hovet, O. et al. Nuclear mechano-confinement induces geometry-dependent HP1α condensate alterations. Commun. Biol. 8, 308 (2025).
3. Nava, M. M. et al. Heterochromatin-Driven Nuclear Softening Protects the Genome against Mechanical Stress-Induced Damage. Cell 181, 800-817.e22 (2020).