Phosphoprocessors
Financiado
Biological signal processing via multisite phosphorylation networks
Multisite phosphorylation of proteins is a powerful signal processing mechanism playing crucial roles in cell division and differentiation as well as in disease. Our goal in this application is to elucidate the molecular basis of...
Multisite phosphorylation of proteins is a powerful signal processing mechanism playing crucial roles in cell division and differentiation as well as in disease. Our goal in this application is to elucidate the molecular basis of this important mechanism. We recently demonstrated a novel phenomenon of multisite phosphorylation in cell cycle regulation. We showed that cyclin-dependent kinase (CDK)-dependent multisite phosphorylation of a crucial substrate is performed semiprocessively in the N-to-C terminal direction along the disordered protein. The process is controlled by key parameters including the distance between phosphorylation sites, the distribution of serines and threonines in sites, and the position of docking motifs. According to our model, linear patterns of phosphorylation networks along the disordered protein segments determine the net phosphorylation rate of the protein. This concept provides a new interpretation of CDK signal processing, and it can explain how the temporal order of cell cycle events is achieved. The goals of this study are: 1) We will seek proof of the model by rewiring the patterns of budding yeast Cdk1 multisite networks according to the rules we have identified, so to change the order of cell cycle events. Next, we will restore the order by alternative wiring of the same switches; 2) To apply the proposed model in the context of different kinases and complex substrate arrangements, we will study the Cdk1-dependent multisite phosphorylation of kinetochore components, to understand the phospho-regulation of kinetochore formation, microtubule attachment and error correction; 3) We will apply multisite phosphorylation to design circuits for synthetic biology. A toolbox of synthetic parts based on multisite phosphorylation would revolutionize the field since the fast time scales and wide combinatorial possibilities.
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Duración del proyecto: 66 meses
Fecha Inicio: 2015-04-07
Fecha Fin: 2020-10-31
Fecha Fin: 2020-10-31
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2020-10-31
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-CoG-2014:
ERC Consolidator Grant
Cerrada
hace 10 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
TARTU ULIKOOL
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
189.52K€ |
Participante