Title of the PhD thesis
Genome instability in meiotic oocyte lacking m⁶A eraser ALKBH5
Main research findings
This thesis examines a chemical tag on RNA, N6‑methyladenosine (m⁶A), and the enzyme ALKBH5 that removes this tag. m⁶A helps control how long messenger RNA molecules (the instructions that guide protein production) persist and how they are used during oocyte maturation. Fully grown oocytes become transcriptionally silent, and therefore they depend on correct post‑transcriptional control of stored RNAs to complete meiosis and support early development.
Using mouse models, we show that loss of ALKBH5 disrupts meiotic chromosome segregation. ALKBH5-deficient oocytes display more segregation errors that are reflected in polar bodies and indicate reduced oocyte quality. At the molecular level, these defects are associated with altered regulation of maternal messenger RNAs, consistent with a failure to remove or appropriately remodel m⁶A marks at the right time.
These findings demonstrate that m⁶A demethylation by ALKBH5 is important for maintaining both genome stability and proper RNA control during oocyte maturation. The work advances our understanding of molecular causes of infertility and points to m⁶A-related processes as potential markers or targets to improve diagnosis and treatments in assisted reproduction.
Trial lecture
The candidate will first give a trial lecture on the following topic:
A tale of two Xs The epigenetic- and epitranscriptomic symphony of gene silencing of X-chromosomes
Adjudication committee
- Lecturer Paul McKeegan, University of Hull, UK
- Associate Professor Mona Nystad, UiT and University Hospital of North Norway, Norway
- Professor Melinka Butenko, Department of Biosciences, University of Oslo, Norway
Chair of the defense
- Professor Rafal Ciosk, Department of Biosciences, University of Oslo, Norway
Supervisors
- Professor Arne Klungland, Centre for Embryology and Healthy Development (CRESCO), Institute of Clinical Medicine, Faculty of Medicine, University of Oslo / Department of Microbiology, Oslo University Hospital, Norway
- Researcher Gareth Greggains, Centre for Embryology and Healthy Development (CRESCO), Institute of Clinical Medicine, Faculty of Medicine, University of Oslo / Department of Microbiology, Oslo University Hospital, Norway
- Group leader Stig Ove Bøe, Department of Microbiology, Oslo University Hospital, Norway
- Professor Pål Falnes, Department of Biosciences, University of Oslo, Norway
Organiser
Department of Biosciences.