(Re-)Writing the Ubiquitin Code – Manipulating Polyubiquitin Chain Linkage to Investigate Ubiquitin Signalling in Genome Maintenance and Beyondcore
UBICODEWRITERS · Horizon Europe grant · 2025-01-01–2029-12-31
EC contribution
Total cost
Beneficiaries
About the data
Source: CORDIS (official EU open data), Horizon Europe. Framework HORIZON · call ERC-2023-ADG · scheme HORIZON-ERC · topic ERC-2023-ADG. CORDIS record →
Objective
Ubiquitylation is an essential posttranslational modification that governs the activities and interactions of cellular proteins. The structural diversity of polyubiquitin chains, collectively called the ubiquitin code, is thought to determine the fate of the modified proteins. Although many analytical and inhibitory ubiquitin-specific reagents exist, we lack the tools to create polyubiquitin chains of defined linkage on a protein of interest in cells to investigate their signalling functions. We recently established a method to induce substrate-specific polyubiquitylation via three major linkages, M1, K48, and K63. Based on this technology, we now propose to develop a new generation of research tools for the scientific community. This will include the identification and design of custom enzymes for assembling the rarer, still poorly characterised non-canonical linkages and a functionalisation with modules for chain editing, branching, and the identification of effectors. In a combination of biochemical, cell biological, and proteomic approaches, we will then apply these tools to major genome maintenance pathways with prominent roles in the defence against disorders such as cancer and premature ageing. Specifically, we will analyse the significance of non-canonical polyubiquitylation in the response to DNA double-strand breaks and the interplay between degradative and non-degradative ubiquitylation in the regulation of essential DNA replication and repair factors. We envision that our research will not only provide new insight into ubiquitin signalling in genome maintenance, but the new technology developed in this project will facilitate future investigations of polyubiquitin chains, their readers, and their writers in other signalling pathways. Situated at the interface between proteostasis and genome maintenance, this project will thus advance our understanding of two essential cellular surveillance systems with critical functions in human health and well-being.
Beneficiaries (1)
| Organisation | Country | Role | EC contribution | SME |
|---|---|---|---|---|
| INSTITUT FUR MOLEKULARE BIOLOGIE GGMBH | DE | coordinator | €2,499,799 |
Get the EU Defence Funding Calendar — free
The full calendar of open EU defence and dual-use funding calls, sorted by deadline, updated nightly. Delivered with DFM Analysis, our weekly briefing on who is funding what in European defence.
Or browse all open defence & dual-use calls on the funding calendar →
Defence Finance Monitor is an analytical and informational product. Grant data is official CORDIS; the paid Annual Professional subscription is handled on DFM Analysis.