Around 30% of the proteome, including secretory proteins, plasma membrane proteins, and proteins targeted to organelles require the endoplasmic reticulum (ER) for their biosynthesis. During translation, ribosomes can stall for several reasons forming stalled ribosome-nascent chain complexes. Ribosome stalling signals a series of steps resulting in decay of defective mRNAs, recycling of stalled ribosomes and importantly degradation of the partially synthesized nascent polypeptide. These quality control pathways are essential for protein homeostasis and deficiencies in these factors are associated with neurodegeneration.
UFM1 is a poorly understood ubiquitin-like modifier that is attached to ER-associated ribosomes. It is believed that stalling of ribosomes at the ER triggers UFMylation and degradation of the stalled ribosome complexes via ER-phagy. Mutations to components of the UFM1 pathway have been identified in several neurodevelopmental disorders highlighting the importance of this modification. This project will build on recent work where we have defined the molecular players involved in the addition and removal of UFM1 from ribosomes1,2. The goal of this project will be to define how ribosomes get UFMylated and to reveal in molecular detail the consequence of UFMylation. This project has the potential to reveal the molecular mechanism of a fundamental pathway essential for secretory protein biogenesis.
The student will get the opportunity to get trained and employ a highly multidisciplinary approach, with techniques including quantitative proteomics, cell biology, biochemistry, structural biology (X-ray crystallography and cryo-EM) and single cell analyses. The PhD student will be responsible for an independent project and will benefit from working closely with more experienced members of the lab.
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.
How to Apply
Please send a CV with contact details of three referees to and a cover letter explaining why you have chosen to apply to MRC PPU to [Email Address Removed]. The closing date for applications is 14th April 2023. Applications from overseas students are welcome.
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