Joshua Peter, a recently graduated PhD student from Yogesh Kulathu’s lab, has been awarded the 2023 Dundee Molecular and Cellular Biology Prize for his work on the poorly understood ubiquitin-like modifier, UFM1.

Discovered in 2004, UFM1 is a relatively new player in the realm of Ubiquitin-like proteins. UFMylation is essential for the synthesis of membrane and secretory proteins, and its malfunction is linked to several developmental and neurological disorders. Joshua's research, conducted in the Kulathu lab at the MRC PPU between 2017 and 2023, has shed light on the enigmatic process of UFM1 attachment to proteins, particularly to ribosomes located at the endoplasmic reticulum – the cellular sites of membrane and secretory protein production.

Through an innovative approach, Joshua reconstituted the UFMylation process in vitro using purified components. He determined that the previously acknowledged E3 ligase for UFMylation, UFL1, is inactive on its own. He discovered that it requires two critical factors, UFBP1 and CDK5RAP3, that interact with UFL1 to form an active E3 ligase complex, challenging previous assumptions about UFMylation. Further, it provides a new paradigm to the conventional understanding of E3 ligases, as UFL1 and UFBP1 are composed of winged helix (WH) domain repeats, typically found in transcription factors, making this a highly unusual E3 ligase complex. Furthermore, he identified that CDK5RAP3, a third component of the complex, unexpectedly inhibits UFL1/UFBP1's activity in vitro, and acts as a substrate adaptor for ribosome UFMylation, effectively functioning as an on-off switch for the ligase complex.

This research not only elucidates the biochemical basis of UFMylation but also unravels the regulatory principles of this atypical E3 ligase complex. Joshua also made important contributions to recent studies to understand the mechanism and function of ribosome UFMylation. For these remarkable contributions, Joshua has been awarded the 2023 Molecular and Cellular Biology Prize. His work has set a solid foundation for future research in this field. Having completed his tenure at the MRC PPU, Joshua has recently embarked on a postdoctoral position in the lab of Prof. Chris Lima at Sloan Kettering/HHMI, where he will undoubtedly continue to make impactful scientific contributions.