The interplay between RNA processing and DNA repair
The nematode Caenorhabditis elegans is a powerful experimental model, which yielded many key discoveries like apoptosis or RNAi. In this project, we will use C. elegans and mammalian cells to understand the connection between RNA processing and DNA repair, with important implications for human cancer
RNA processing is critical for gene expression and various molecular pathways ensure its fidelity. One such pathway is the nonsense-mediated mRNA decay (NMD), which degrades certain types of incorrect mRNAs - typically containing premature stop codons. In a genetic screen, aimed at isolating new players in the NMD pathway, we identified CLK-2. This was surprising, since CLK-2 (mammalian TEL2) has been previously implicated in DNA damage and telomere maintenance, but not NMD. Nevertheless, recent work suggests that the core components of NMD are critical also for the DNA repair. How the NMD machinery facilitates DNA repair remains unknown and is the focus of this project.
In examining the role of CLK2, and the connection between NMD and DNA repair, you will use the CRISPR-Cas9 gene editing to tag and create mutations in specific C. elegans genes, and analyze the resulting phenotypes. You will also use fluorescent microscopy to examine the distribution of molecular players, as well as prepare and analyze RNAseq samples to understand changes in RNA processing associated with DNA repair. In this project, you will work in close collaboration with Drs. Yanwu Guo and Pooja Kumari.
The laboratory and contact
The Ciosk laboratory <https://www.mn.uio.no/ibv/english/people/aca/rafalc/>, is located at the Department of Biosciences, Section of Molecular Biology and Biochemistry. Interested students please contact Rafal Ciosk as soon as possible.
Office: Kristine Bonnevies hus, Blindernvn. 31, Room. 2110