Approximately one third of the human proteome depends on the endoplasmic reticulum (ER) for its biosynthesis. During translation, ribosomes can sometimes stall, triggering a chain of events that results in the decay of defective mRNAs, recycling of stalled ribosomes and crucially, degradation of partially synthesized nascent polypeptides. UFM1 is an enigmatic ubiquitin-like modifier that is attached to ER-associated ribosomes when stalling occurs. The role of this UFM1 attachment is not fully understood, but mutations in the UFM1 pathway have been found in several neurodevelopmental disorders, emphasizing its significance.

The goal of this project is to define how ribosomes get UFMylated upon stalling and to investigate the mechanisms and function of ribosome UFMylation. This project will build on our recent unpublished work, and we are looking for curious and creative students to work at the frontier of an exciting new field. What makes this project especially exciting is its potential to reveal a fundamental pathway responsible for quality control and homeostasis at the ER, the disruption of which causes disease.

You will get the opportunity to learn and employ a wide array of scientific techniques, including quantitative proteomics, genome wide CRISPR screens, cell biology, biochemistry, and single cell analyses. While working on an independent project, you will benefit from working closely with experienced lab members. If you are driven by curiosity and a desire to explore the uncharted territories of cellular biology, we invite you to apply.

References

1. Peter, JJ et al. (2022) A non-canonical scaffold-type E3 ligase complex mediates protein UFMylation. EMBO J.
2. Milrine et al. (2022). Human UFSP1 is an active protease that regulates UFM1 maturation and UFMylation. Cell Reports. 40(5):111168
3. Millrine D, Peter JJ and Kulathu Y. (2023). A guide to UFMylation, an emerging posttranslational modification. FEBS J.

At the MRC PPU, as well as the possibility of a PhD in one particular lab, we offer the possibility of two 4.5-month rotations in labs of their choice. A range of other projects from MRC PPU scientists are advertised on this website. Rotations provide valuable experience and help with deciding on the choice of PhD project and research group.