Melanie Lianne Engelfriet

• Engelfriet, Melanie Lianne; Guo, Yanwu; Arnold, Andreas; Valen, Eivind & Ciosk, Rafal (2025). Reprograming gene expression in ‘hibernating’ C. elegans involves the IRE-1/XBP-1 pathway. eLIFE. 13. doi: 10.7554/elife.101186.3. Full text in Research Archive Show summary

  In nature, many animals respond to cold by entering hibernation, while in clinical settings, controlled cooling is used in transplantation and emergency medicine. However, the molecular mechanisms that enable cells to survive severe cold are still not fully understood. One key aspect of cold adaptation is the global downregulation of protein synthesis. Studying it in the nematode Caenorhabditis elegans , we find that the translation of most mRNAs continues in the cold, albeit at a slower rate, and propose that cold-specific gene expression is regulated primarily at the transcription level. Supporting this idea, we found that the transcription of certain cold-induced genes is linked to the activation of unfolded protein response (UPR) through the conserved IRE-1/XBP-1 signaling pathway. Our findings suggest that this pathway is triggered by cold-induced perturbations in proteins and lipids within the endoplasmic reticulum, and that its activation is beneficial for cold survival.

• Engelfriet, Melanie Lianne; Malecki, Jedrzej Mieczyslaw; Forsberg, Frida; Falnes, Pål & Ciosk, Rafal (2023). Characterization of the biochemical activity and tumor-promoting role of the dual protein methyltransferase METL-13/METTL13 in Caenorhabditis elegans. PLOS ONE. 18(6), p. 1–16. doi: 10.1371/journal.pone.0287558. Full text in Research Archive Show summary

  The methyltransferase-like protein 13 (METTL13) methylates the eukaryotic elongation factor 1 alpha (eEF1A) on two locations: the N-terminal amino group and lysine 55. The absence of this methylation leads to reduced protein synthesis and cell proliferation in human cancer cells. Previous studies showed that METTL13 is dispensable in non-transformed cells, making it potentially interesting for cancer therapy. However, METTL13 has not been examined yet in whole animals. Here, we used the nematode Caenorhabditis elegans as a simple model to assess the functions of METTL13. Using methyltransferase assays and mass spectrometry, we show that the C . elegans METTL13 (METL-13) methylates eEF1A (EEF-1A) in the same way as the human protein. Crucially, the cancer-promoting role of METL-13 is also conserved and depends on the methylation of EEF-1A, like in human cells. At the same time, METL-13 appears dispensable for animal growth, development, and stress responses. This makes C . elegans a convenient whole-animal model for studying METL13-dependent carcinogenesis without the complications of interfering with essential wild-type functions.

• Schoot, Johan M. S. van der; Fenneman, Felix L.; Valente, Michael; Dolen, Yusuf; Hagemans, Iris M. & Becker, Anouk M. D. [Show all 21 contributors for this article] (2019). Functional diversification of hybridoma-produced antibodies by CRISPR/HDR genomic engineering. Science Advances. 5(8). doi: 10.1126/sciadv.aaw1822. Full text in Research Archive

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