Main supervisor: Ragnhild Eskeland (IMB and Centre for Cancer Cell Reprogramming)
Co-supervisors: Nikolina Sekulic (IMB)
Internal supervisor: Cinzia Progida (IBV)
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
The DNA a eukaryotic cell has a total length of about two meters and is packaged in such a way that it fits in the nucleus. To achieve this, the DNA is wrapped around an octamer of histone proteins to form a nucleosome. This histone octamer consists of two each of the four types of core histones: H2A, H2B, H3 and H4 (Luger et al., 1997). These beads on a string are looped and coiled tightly to form chromatin fiber and eventually chromosomes, leading to a compaction that fits in the nucleus. Bacteria were long thought to have free circular DNA without any packing, however recently it was shown that Archaea have homologous proteins to histones (Mattiroli et al., 2017). Surprisingly, also viruses also were found to pack the DNA around histone proteins (Schwab et al., 2026). Histones are conserved and fundamental proteins across evolution and plays a crucial role in organizing DNA. In this master project we focus on novel protein that has histone like similarities. The student will characterize these proteins and the interaction with and folding of DNA. This implies learning AI prediction, molecular and biochemical methods and understanding of novel biological functions.
Tasks
Alphafold server has become a powerful tool for prediction of protein interaction with DNA and will be used to study the histone like protein candidates. The student will work with molecular cloning and protein expression in bacteria. Furthermore, the proteins will be purified by FPLC column purification. Many assays for DNA binding will be used to assess the histone like function of this novel protein including EMSA and pulldown. Data generated will be plotted and visualized with Graphpad. For interesting histone-like protein candidates we aim to perform CryoEM.
We seek a highly motivated and hardworking master student to make novel discoveries on proteins with potential for biotechnological methodology development. This thesis will expose the master student to a whole range of wet lab work and the most recent molecular and biochemical techniques.
Value of research outcome
In recent years we have learned that also some bacteria and viruses pack their DNA into histone like proteins. The student will characterize a novel histone like protein and describe its function as a DNA binder by biochemical tools. We will learn more about the molecular function of a novel histone protein candidate that will give new knowledge about viral infection.
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
Luger, K., Mäder, A.W., Richmond, R.K., Sargent, D.F., Richmond, T.J., 1997. Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 389, 251–260. https://doi.org/10.1038/38444
Mattiroli, F., Bhattacharyya, S., Dyer, P.N., White, A.E., Sandman, K., Burkhart, B.W., Byrne, K.R., Lee, T., Ahn, N.G., Santangelo, T.J., Reeve, J.N., Luger, K., 2017. Structure of histone-based chromatin in Archaea. Science 357, 609–612. https://doi.org/10.1126/science.aaj1849
Schwab, S., Olsthoorn, M., Jansen, T., Dame, R.T., 2026. ProHistoneDB: A database of prokaryotic and viral histones. Journal of Molecular Biology 169644. https://doi.org/10.1016/j.jmb.2026.169644