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UBICODEWRITERS

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Re Writing the Ubiquitin Code Manipulating Polyubiquitin Chain Linkage to In...

Re Writing the Ubiquitin Code Manipulating Polyubiquitin Chain Linkage to Investigate Ubiquitin Signalling in Genome Maintenance and Beyond 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 though... ver más

31/12/2029

IMB

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

INSTITUT FUR MOLEKULARE BIOLOGIE GGMBH No se ha especificado una descripción o un objeto social para esta compañía.

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-06-24

ERC-2023-ADG: ERC ADVANCED GRANTS Scope:Objectives

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1 Participantes

IMB

2.50M€ | Lider

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Duración del proyecto: 66 meses Fecha Inicio: 2024-06-24
Fecha Fin: 2029-12-31

Líder del proyecto

INSTITUT FUR MOLEKULARE BIOLOGIE GGMBH No se ha especificado una descripción o un objeto social para esta compañía.

Presupuesto del proyecto 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto 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.

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