StressHUb
Financiado
Defining mechanisms of cellular stress responses driven by heterotypic ubiquitin...
Posttranslational modification of proteins with monoubiquitin or different polyubiquitin chains alter protein function to signal distinct responses in cells and thereby regulate every aspect of eukaryotic biology. Recently, ubiqui...
Posttranslational modification of proteins with monoubiquitin or different polyubiquitin chains alter protein function to signal distinct responses in cells and thereby regulate every aspect of eukaryotic biology. Recently, ubiquitin has also been reported to form branched heterotypic chains. The central premise of this proposal is that branched ubiquitin chains adopt unique conformations and convey distinct intracellular signals essential for maintaining cellular homeostasis. We posit that branching of homotypic ubiquitin chains or de novo formation of branched structures occurs in response to specific cues and they serve as priority signals to mediate prompt cellular responses. The complex nature of branched heterotypic ubiquitin, the lack of tools to specifically and efficiently probe different branched ubiquitin structures and the relatively low abundance of these chains in a cell make it challenging to study them. In this proposal, I will describe an ambitious approach to define how branched ubiquitin serve as unique signals to elicit cellular stress responses. To attain these goals, we will pioneer the development of novel designer tools and methods, which we will combine with quantitative proteomics, single cell analyses, biochemistry and structural biology. We will elucidate the molecular players involved in the assembly, decoding and regulation of branched ubiquitin. We will develop approaches to monitor branched ubiquitin formation in cells to identify stress conditions that trigger formation of branched ubiquitin chains. We will functionally characterize how distinct branched heterotypic ubiquitin signals are formed in response to stress and serve as priority signals to trigger stress-response pathways. Our work will shed light on fundamental principles of intracellular signalling and mechanisms that maintain cellular homeostasis.
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Duración del proyecto: 68 meses
Fecha Inicio: 2021-04-21
Fecha Fin: 2026-12-31
Fecha Fin: 2026-12-31
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2021-04-21
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2020-COG:
ERC CONSOLIDATOR GRANTS
Cerrada
hace 4 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
UNIVERSITY OF DUNDEE
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
262.80K€ |
Participante