Supervisors
Main supervisor: Ragnhild Eskeland (IMB)
Co-supervisors: Andrea Halaburkova (IMB)
Internal supervisor: Cinzia Progida
This master project is part of a Centre of Excellence at UiO, the Centre for Cancer Cell Reprogramming (https://www.med.uio.no/cancell/english/).
Background
Cancer causes approximately 10,000 deaths annually in Norway. Due to cancer research, we are continually gaining new knowledge that contributes to better diagnosis and treatment. Sarcoma is a rare type of cancer that occurs in bones and connective tissue. There are about fifty different subgroups of this cancer type, and sarcoma patients are often young with generally poor prognosis. The treatment usually involves a combination of surgery, chemotherapy, and radiation therapy. These treatment forms can be painful and have significant side effects, and unfortunately, they are not always effective. The lack of detailed knowledge about differences in sarcoma cell types, the lack of biomarkers, as well as difficulties in determining the grade of malignancy, currently hinder effective and personalized treatment. More research is needed in this area.
Project
Rhabdomyosarcoma is a soft tissue cancer that annually affects three to six Norwegian children (Cancer Registry of Norway). Paediatric cancers have generally low mutation burden and therefore these cancers are driven by deregulation of epigenetics and transcription(Chen et al., 2024). In the Chromatin Biology group, we work to gain molecular knowledge about epigenetic drivers in rhabdomyosarcoma. It is known that changes in gene expression can contribute to cancer development, and it has been shown that epigenetic factors can influence such changes. It is also known that cancer-promoting factors can affect gene expression through epigenetic modifications such as EZH2 (O’Brien et al., 2023). We focus on identifying such factors involved in the development of rhabdomyosarcoma, and we have already found epigenetic factors that promote cancer progression. We will now test chemical and genetic inhibitors of these factors in rhabdomyosarcoma patient cell lines and a tumoroid cancer model. With this project, the master student will be able to help provide us with new and important knowledge that can ultimately make a difference for children with this serious cancer type.
Methods
The student will learn protein purification, mammalian tissue culture including culture of tumoroids, various molecular and immunological methods such as cloning, transfection, western blotting, immunofluoresence and confocal imaging. The student will apply CRISPR-Cas9 genome editing and knockdown of target genes (RNAi/CRISPRi/degron system) in presence of epigenetic drugs.
About you
We are looking for a driven, enthusiastic and hardworking student. You should be motivated to learn, have good collaborative skills and be involved in developing new methods. An interest in microscopy is essential.
About us
During this master project you will be part of our Chromatin Biology Group (www.chromatome.no). You will learn to make good scientific presentations, have creative discussions and will be able to attend national scientific retreats as a part of a young active ambitious research group. You will be participating in a Centre of Excellence “Centre for Cancer Cell Reprogramming” at UiO (https://www.med.uio.no/cancell/english/) and part of the master project will be at the Medical Faculty, UiO. We will also train you in good scientific writing.
To learn more about our lab visit: https://www.youtube.com/watch?v=6yADYLbFEo4&feature=youtu.be
References
Chen, X., Yang, W., Roberts, C.W.M., Zhang, J., 2024. Developmental origins shape the paediatric cancer genome. Nat Rev Cancer 24, 382–398. https://doi.org/10.1038/s41568-024-00684-9
O’Brien, E., Tse, C., Tracy, I., Reddin, I., Selfe, J., Gibson, J., Tapper, W., Pengelly, R.J., Gao, J., Aladowicz, E., Petts, G., Thway, K., Popov, S., Kelsey, A., Underwood, T.J., Shipley, J., Walters, Z.S., 2023. Pharmacological EZH2 inhibition combined with retinoic acid treatment promotes differentiation and apoptosis in rhabdomyosarcoma cells. Clinical Epigenetics 15, 167. https://doi.org/10.1186/s13148-023-01583-w