Understanding the physiological role of METTL9 and developing inhibitors

Background

Zinc is an essential micronutrient playing fundamental roles in a wide range of biological processes. An imbalance in zinc homeostasis has been linked to a range of health issues, including cancer, gastrointestinal disease, and diabetes (Kiouri et al., 2023). Zinc levels are tightly regulated by the absorption, secretion, and excretion via specialized zinc transporter proteins in the intestine. Many zinc transporters are methylated on zinc-binding histidine residues by the METTL9 methyltransferase (Davydova et al., 2021), and we hypothesize that this enzyme may act as a master regulator of zinc transport.

Our research goals are to elucidate the physiological functions of METTL9 using advanced methods such as cell culture, organoids, and mouse models. Furthermore, we will explore METTL9's roles in cancer and other diseases and aim to develop specific inhibitors targeting its enzymatic activity.

Bildet kan inneholde: diagram.

Methodology

As a master student in our laboratory, you will be trained in a wide range of experimental techniques essential for modern biomedical research.

  • 2D cell culture: Including CRISPR-Cas knockout, for fundamental cellular studies.
  • 3D organoid culture: To model complex tissue architecture and function. See Figure 1 for the workflow of organoid generation.
  • In vivo mouse techniques: Learn mouse handling and dissection methods to work with live models.
  • Imaging techniques: Develop skills in immunofluorescence staining and confocal microscopy to visualize localization of molecules and tissue structure. See Figure 2 to get a glimpse of the types of models and imaging approaches we will use.
  • Molecular biology methods: Gain hands-on experience with recombinant protein expression, and enzymatic assays for our inhibitor project.

We are looking for highly motivated and curious master’s students to join our group!

Main supervisors

Naveen Parmar: naveen.parmar@medisin.uio.no

Erna Davydova: erna.davydova@ibv.uio.no

References

Kiouri, Despoina P., et al. "Multifunctional role of zinc in human health: an update." EXCLI journal 22 (2023): 809.

Davydova, Erna, et al. "The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes." Nature communications 12.1 (2021): 891.

 

 

 

Publisert 2. juli 2025 11:50 - Sist endret 2. juli 2025 11:50

Veileder(e)

Omfang (studiepoeng)

60